Methods

See Barrett‐Connor 1999

Participants

See Barrett‐Connor 1999

Interventions

See Barrett‐Connor 1999

Outcomes

See Barrett‐Connor 1999

Notes

See Barrett‐Connor 1999

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Barrett‐Connor 1999

Allocation concealment?

Low risk

See Barrett‐Connor 1999

Blinding?
All outcomes

Low risk

See Barrett‐Connor 1999

Incomplete outcome data addressed?
All outcomes

High risk

See Barrett‐Connor 1999

Free of selective reporting?

High risk

See Barrett‐Connor 1999

Free of other bias?

Low risk

See Barrett‐Connor 1999

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: multicentre
‐Duration: 2 years
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 331; E group 79, E‐T group 81, E(high dose) group 78, E‐T(high dose) 73
‐No of participants completed the study: 199
‐No of participants analysed: depended on outcomes, 196 for lipid profile, unclear for other outcomes.
‐No of noncom pliers: 122/311= 39.2%; Reasons were adverse events(45), non‐drug event(24), protocol violation(21), lost to follow up (22)
‐No of losses to follow up: 22/311=7.1%
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Location: US
‐Setting: hospital‐based
‐Ethnicity: Caucasians
‐Run‐in period: no
‐Characteristics: healthy surgically menopausal women
‐Age (SD): E(low dose) group 46.5 (7.5), E‐T(low dose) group 44.8 (8.1), E(high dose) group 45.1 (7.1), E‐T(high dose) group 46.3 (7.8)
‐Inclusion criteria:
1. Caucasian
2. Age 21‐65 years
3. TAH with BSO at least 3 months but not more than 5 years
4. Body weight within 75‐125% of ideal body weight
5. A stable personal relationship for at least 6 months
‐Exclusion criteria:
1. Use of estrogen or hormone therapy in the previous six weeks
2. Use of psychotropic drugs in the previous four weeks
3. History of pelvic or breast malignancy
4. Dependence on alcohol, tobacco or illicit drugs

Interventions

‐CEE 0.625 mg once a day
‐CEE 1.25 mg once a day (high dose)
‐CEE 0.625 mg plus mT 1.25 mg once a day
‐CEE 1.25 mg plus mT 2.5 mg once a day (high dose)
‐Route:oral
‐Co‐intervention: all participants received calcium supplement

Outcomes

‐Relevant outcomes:
1. General well being
2. Sexual behavior and enjoyment
3. BMD of lumbar spines and hip: DEXA
4. Menopausal symptoms: scales modified from those developed by Sherwin and Kupperman
5. Lipid profile
6. Haematocrit
‐Other outcomes:
1. Other safety outcomes

Notes

‐Baseline equality: no differences in mean age, weight, height, body mass index and duration of menopause in four treatment groups. There was no report of the baseline equality of groups for the outcome of interest.
‐The author was contacted. The further supplied information was not allowed by drug company.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Discontinuation >10%

Free of selective reporting?

High risk

Acne data reported incompletely

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

See Dobs 2002

Participants

See Dobs 2002

Interventions

See Dobs 2002

Outcomes

See Dobs 2002

Notes

See Dobs 2002

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Dobs 2002

Allocation concealment?

Low risk

See Dobs 2002

Blinding?
All outcomes

Unclear risk

See Dobs 2002

Incomplete outcome data addressed?
All outcomes

Unclear risk

See Dobs 2002

Free of selective reporting?

Unclear risk

See Dobs 2002

Free of other bias?

Unclear risk

See Dobs 2002

Methods

‐Design: double‐blind randomised (C), parallel group
‐No. of centres: multicentre
‐Duration: 24 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: available case analysis
‐No. of participants randomised:447(119 in E group, 107 in E‐T150, 110 in E‐T300, 111 in E‐T450)
‐No. of participants completed the study: E group 81/119(68%), E‐T150 72/107(67%), E‐T300 81/110(74%), E‐T450 85/111(77%), overall 319/447(71%)
‐No. of participants analysed: not stated
‐No. of non compilers: E group 32%. Reasons were adverse event(12%), voluntary(10%), other(10%); E‐T150 33%. Reasons were adverse event(13%), voluntary(8%), other(11%); E‐T300 26%. Reasons were adverse event(7%), voluntary(10%), other(9%); E‐T450 23%. Reasons were adverse event(10%), voluntary(7%), other(6%)
‐No of losses to follow up: E group10/119 (0.6%); E‐T150 8/107 (0.7%) ; E‐T300 7/110 (0.6%); E‐; E‐T450 7/111 (0.6%)
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: surgically menopausal women with menopausal onset of low sexual desire with low serum T levels
‐Age: E group 49, E‐T150 group 50, E‐T300 group 50, E‐T450 group 49
‐Location: US
‐Setting: population‐based
‐Ethnicity: Caucasian 89%
‐Run‐in period: 8‐week pretreatment baseline period
‐Inclusion criteria:
1. 20‐70 year‐old
2. Generally good health
3. BMI 18‐30 kg/m²
4. TAH with BSO at least 1 year
5. Stable relationship with partner present more than 50% of the time
6. Serum free‐T < 3.5 pg/ml at baseline
7. Stable estrogen dose > 3 months
8. Menopause onset of low sexual desire
‐Exclusion criteria:
1. >15 moderate to severe hot flushes per week
2. Recent androgen use
3. Hirsutism, virilization, severe acne
4. Positive screening for depression or hypothyroidism
5. Ongoing medical, psychiatric or relationship disturbance
6. Medications known to affect sexual function
7. Severe hyperlipidaemia/metabolic disorders
8. Dyspareunia, physical limitations affecting sexual function

Interventions

‐ once a day ‐CEE once a day plus T 150 mg twice a week
‐CEE once a day plus T 300 mg twice a week
‐CEE plus T 450 mg
‐Route:oral oestrogen, transdermal T patch
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function: SAL and PFSF
2. Hirsutism
3. Acne
‐Other outcomes:
1. Safety outcomes(adverse events, clinical laboratory measurements, vital signs, and physical examinations.

Notes

‐Baseline equality: no statistically significant differences across treatment groups with regard to age, ethnicity, percent married to partner, duration of relationship, age at oophorectomy and years since oophorectomy
‐The author was contacted. The further information was supplied.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possibly free of other sources of bias

Methods

‐Design: single‐blind randomised (A), parallel group
‐No of centres: two
‐Duration: 24 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 20 (10 in each group)
‐No of participants completed: 18/20 = 90%
‐No of participants analysed: not stated
‐No of non compilers: 2/10=20%
‐No of losses to follow up: not stated
‐Compliance assessment: not stated
‐Source of funding: drug company provided medication

Participants

‐Location:Australia
‐Setting:hospital‐based
‐Ethnicity:unspecified
‐Run‐in period:current treatment with oral estrogens was stopped for a duration of 2 weeks
‐Characteristics:surgically(9 in E‐T, 10 in E group) and naturally (1 in E‐T group) menopausal women with loss of libido despite treatment of oral estrogens‐progestogens
‐Age(SD):E group 48.2(5.2), E‐T group 43.5(7.6)
‐Inclusion criteria: as above
‐Exclusion criteria: not stated

Interventions

‐oestradiol 40 mg
‐oestradiol 40 mg plus T 50 mg
‐Route: implant
‐Co‐intervention: norethisterone 2.5 mg daily for 10 days every month was prescribed for women with intact uterus

Outcomes

‐Relevant outcomes:
1. Libido:self‐rating analogue scales(0‐100)
2. Sexual enjoyment: 0‐3 rating scale
‐Other outcomes:
1. Plasma testosterone

Notes

‐Baseline equality: the mean number of years since menopause of the single and combined implant were 5.6(3.9) and 7.8(4.8), respectively. Nine of the combined implant group and all 10 in the single implant group had had hysterectomies, and three from each group had had oophorectomies.
‐The author was contacted and kindly supplied further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Outcome assessment was blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

High risk

One or more outcomes of interest in the review (sexual function) are reported incompletely

Free of other bias?

Unclear risk

insufficient information

Methods

‐Design: double‐blind randomised(A), parallel group
‐No of centres: multicentre
‐Duration: 24 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: available case analysis
‐No of participants randomised: 533 (266 in E group, 267 in E‐T)
‐No of participants completed the study: 417 (206 in E group, 211 in E‐T)
‐No of participants analysed: 532
‐No of non compilers: E group 49/266 (18.4%). Reasons were adverse event (22), voluntary (25), protocol violation (2); E‐T 50/267 (18.7%). Reasons were adverse event (22), voluntary (22), protocol violation (6)
‐No of losses to follow up: 16/533 (3.0%); E group 11, E‐T group 5
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: surgically menopausal women with menopausal onset of hypoactive sexual desire disorder
‐Age: E group 49.5+7.55, E‐T group 48.3+7.45 yr
‐Location: US
‐Setting: population‐based
‐Ethnicity: E group African American 14 (5%), White 244 (92%), Hispanic 7 (3%), other 1 (<1%); E‐T group African American 13 (5%), White 237 (89%), Hispanic 11 (4%), other 5 (2%)
‐Run‐in period: 8 week pretreatment baseline period
‐Inclusion criteria:
1. 20‐70 year old
2. Generally good health
3. BMI 18‐30 kg/m²
4. TAH with BSO at least 1 year
5. Stable monogamous relationship for at least 1 year to a sexually (both psychologically and physically) functional partner who was available for sexual activity at least 50% of each month during the study
6. Stable oral or transdermal estrogen dose > 3 months
7. Hypoactive sexual desire disorder
‐Exclusion criteria:
1. Recent androgen use
2. Hirsutism, virilization, severe acne
3. Positive screening for depression or hypothyroidism
4. Ongoing medical, psychiatric or relationship disturbance
5. Medications known to affect sexual function
6. Severe hyperlipidaemia/metabolic disorders
7. Dyspareunia, physical limitations affecting sexual function

Interventions

‐ Oral or transdermal oestrogen plus T patch 300 microgram/d
‐ Oral or transdermal oestrogen plus placebo patch
‐ Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function: SAL and PFSF
2. Lipid profile
3. Hirsutism
4. Acne
‐Other outcomes:
1. Safety outcomes

Notes

‐Baseline equality: no statistically significant differences across treatment groups with regard to mean age, ethnicity, percent married to partner, duration of relationship, route of oestrogen, and body mass index
‐The author was contacted. The further information was supplied.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (C), parallel group
‐No. of centres: multicentre
‐Duration: 10 weeks
‐Power calculation: no
‐Intention‐to‐treat analysis: available case analysis
‐No of participants randomised:84
‐No of participants completed the study: Not stated
‐No of participants analysed: 79
‐No of non compilers: not stated
‐No of losses to follow up: not stated
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: surgically menopausal women with menopausal onset of low sexual desire with low serum T levels
‐Age:E group 49, E‐T150 group 50, E‐T300 group 50, E‐T450 group 49
‐Location:US
‐Setting:population‐based
‐Ethnicity: Caucasian 89%
‐Run‐in period: 8‐week pretreatment baseline period
‐Inclusion criteria:
1. TAH with BSO >3 months
2. Stable relationship for > 2 years
3. Serum free‐T < 2 pg/ml at baseline
4. Stable estrogen dose (oral, topical, transdermal) > 3 months
‐Exclusion criteria:
1. A medical history or current diagnosis of known sensitivity or contraindications to hormone therapy with estrogens or androgens
2. Major mental illness or an eating disorder within the past 2 yr
3. BMI of 35 kg/m² or more
4. Current or prior history of cardiovascular disease
5. Clinically significant haematological, autoimmune, endocrine, renal, gastrointestinal, or neurological disorder
6. Current history of breast cancer or breast cancer in an identical twin
7. Malignant melanoma or any cancer diagnosed < 5 yr
8. Uncontrolled hypertension or poorly controlled diabetes mellitus
9. Gall bladder disease or gallstones
10. Drug or alcohol abuse within the past 6 months before screening
11. Life‐threatening illness
12. Undiagnosed abnormal vaginal bleeding
13. Malignancy of the genital organs.
14. Abnormal physical or laboratory findings included abnormal vaginal cytology, abnormal mammographic findings, abnormal TSH levels, haematocrit < 30%, fasting serum glucose > 140 mg/dl, fasting serum triglycerides > 300 mg/dl, and fasting creatinine > 2.0 mg/dl.
15. Taking any of the following medications: progestin; androgen; glucocorticoid therapy; alternative estrogen‐like agents (such as phytoestrogens); selective oestrogen receptor modulators; liver enzyme‐inducing medications such as rifampicin, phenytoin, barbiturates, antidepressants, and anxiolytics; anticoagulants; or cholesterol‐lowering medications.

Interventions

‐ Methyltestosterone (2.5 mg) plus esterified oestrogens (1.25 mg) compared with esterified oestrogens (1.25 mg) alone
‐Route:oral oestrogen and testosterone, transdermal T patch
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Lipid profile
2. Hirsutism
3. Acne
4. Discontinuation rate
‐Other outcomes:
1. Hormone levels

Notes

‐Baseline equality: no significant differences across treatment groups with regard to age, BMI, race, years since surgical menopause, FSH and TSH. Baseline triglyceride levels were shown in a table. Triglyceride levels were somewhat lower in the T‐HT group than those in the HT group.
‐The author was contacted. No additional information was supplied.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possibly free of other sources of bias

Methods

‐Design: single‐blind randomised (A), parallel group
‐No of centres: single
‐Duration: 2 years
‐Power calculation:not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised:34(17 in each group)
‐No of participants completed: 32/34 = 94.1%
‐No of participants analysed: 33/34 = 97.1% at 12 months(17 in E group, 16 in E‐T group), 32/34 = 94.1% at 24 months(17 in E group, 15 in E‐T group).
‐No of noncom pliers: 2/34=5.9%. One woman discontinued for personal reasons early after commencement, and the other discontinued after 12 months because of weight gain.
‐Compliance assessment:‐
‐Source of funding: not stated

Participants

‐Location: Australia
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Characteristics: surgically and naturally menopausal women with indication for implants
‐Age (SD): E group 51.3 (5.7), E‐T group 57.0 (5.2) yr
‐Inclusion criteria:
1. Postmenopausal women who had been on oral estrogen therapy at least 6 weeks and had an indication for an implant
‐Exclusion criteria:
1. Serious endocrine disorders with systemic disease
2. Use of drugs which affect response to treatment
3. History of alcohol or drug abuse
4. A rapidly progressive fatal disease
5. Major contraindication to HT
6. Other abnormal findings which might affect the interpretation of the result.

Interventions

‐oestradiol 50 mg every three month
‐oestradiol 50 mg plus T 50 mg every three months
‐Route: implant
‐Co‐intervention: women with an intact uterus were treated with either cyclical MPA 5‐10 mg or norethisterone 2.5 mg orally for 12 days per months

Outcomes

‐Relevant outcomes:
1. Sexual function: Sabbatsberg self‐rating scale
2. BMD of lumbar spines and hip: DEXA
3. Lipid profile
‐Other outcomes:
1. Implant accumulation

Notes

‐Baseline equality: no differences in smoking, alcohol habits, hysterectomy, oophorectomy, BMI, or baseline values of sexual function, lipid or hormone in two groups. However the mean age of the E group was less than that of the E‐T group. The mean BMDs were significantly lower for the E‐T group compared to the E group.
‐The author was contacted and kindly provided additional information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Outcome assessment was blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Baseline imbalance (age, bone mineral density)

Methods

See Davis 2006

Participants

See Davis 2006

Interventions

See Davis 2006

Outcomes

See Davis 2006

Notes

See Davis 2006

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Davis 2006

Allocation concealment?

Low risk

See Davis 2006

Blinding?
All outcomes

Low risk

See Davis 2006

Incomplete outcome data addressed?
All outcomes

Low risk

See Davis 2006

Free of selective reporting?

Unclear risk

See Davis 2006

Free of other bias?

High risk

See Davis 2006

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: multicentre
‐Duration: 24 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: available case analysis
‐No of participants randomised: 77 (40 in E group, 37 in E‐T group)
‐No of participants completed the study: 61; E group 31/40 (77.5%), E‐T 30/37 (81.1%)
‐No of participants analysed: primary end point (total satisfying activity ) 72, secondary end point (sexual desire) 69
‐No of noncom pliers: E group 7/40 (32%). Reasons were adverse event 4 (10%), voluntary 2 (5%), protocol violation 1 (2.5%); E‐T 6/37 (16.2%). Reasons were adverse event 3 (8.1%), voluntary 3 (8.1%)
‐No of losses to follow up: E group 1/40 (2.5%), E‐T group 1/37 (2.7%)
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: surgically menopausal women with menopausal onset of low sexual desire with low serum T levels
‐Age: E group 49.3(30‐63), E‐T 51.0(38‐66) yr
‐Location: Australia, UK, France, Germany, Netherlands, Italy
‐Setting: population‐based
‐Ethnicity: unclear
‐Run‐in period: 8‐week pretreatment baseline period
‐Inclusion criteria:
1. 20‐70 year‐old
2. Generally good health
3. BMI 18‐30 kg/m²
4. TAH with BSO at least 1 year
5. Stable relationship with partner present more than 50% of the time
6. Serum free‐T < 3.5 pg/ml at baseline
7. Stable estrogen dose > 3 months
8. Menopause onset of hypoactive sexual desire disorder
‐Exclusion criteria:
1. >15 moderate to severe hot flushes per week
2. Recent androgen use
3. Hirsutism, virilization, severe acne
4. Positive screening for depression or hypothyroidism
5. Ongoing medical, psychiatric or relationship disturbance
6. Medications known to affect sexual function
7. Severe hyperlipidaemia/metabolic disorders
8. Dyspareunia, physical limitations affecting sexual function

Interventions

‐ Transdermal oestrogen plus T 150 microgram/d
‐ Transdermal oestrogen
‐ Route: transdermal oestrogen patch, transdermal T patch
‐ Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function
2. Hirsutism
3. Acne
‐Other outcomes:
1. Safety outcomes(adverse events)

Notes

‐Baseline equality: no significant differences across treatment groups with regard to age, BMI, duration of relationship, and years since oophorectomy. However, there is somewhat different in frequency of total satisfactory activity.
‐The author was contacted. The further information was supplied.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Baseline imbalance (sexual function)

Methods

‐Design: a randomised, double‐blind, placebo‐controlled and crossover trial
‐No. of centres: single
‐Duration: 16 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: no
‐No. of participants randomised: 85
‐No. of participants completed/analysed: 80
‐No. of non compilers: Five participants ceased to participate in this study because of abnormal uterine bleeding (n = 1) and private reasons (n = 4)
‐Compliance assessment: not stated
‐Source of funding: not stated

Participants

‐Location: Sao Paulo, Brazil
‐Setting: hospital‐based
‐Ethnicity: Caucasian
‐Run‐in period: no
‐Characteristics: naturally menopausal women with sexual dysfunction
‐Age: 49‐63 yr
‐Inclusion criteria:
1.Women had to report complaints of sexual dysfunction acquired in the postmenopausal period and to regularly use HRT. 2. Sexually active and satisfied with the performance of their partners.

‐Exclusion criteria 1. Use of other medication 2. Having other health problems or postmenopausal symptoms that could interfere with their sexual life including hot flashes, insomnia and other psychosomatic symptoms.

Interventions

Methyltestosterone 2.5 mg/day combined with HRT (conjugated equine oestrogens 0.625 mg/day plus medroxyprogesterone acetate 5 mg/day) versus HRT (conjugated equine oestrogens 0.625 mg/day plus medroxyprogesterone acetate 5 mg/day)

Outcomes

Lipid profile, sexual function, acne, hair growth, nervousness, aggressiveness, and discontinuation rate

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Unclear risk

B‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Crossover trial, no washout period

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single
‐Duration: 16 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 40(20 in each group)
‐No of participants completed/analysed: 37(92.5%); 19 in E group, 18 in E‐T group
‐No of noncompliers: 3/40 = 7.5%. Reason was adverse events(two in the E‐T group, one in E group)
‐Compliance assessment: not stated
‐Source of funding:partly funded by drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: White (85%), Hispanic (5%), Black (2%)
‐Run‐in period: no
‐Characteristics: healthy surgically and naturally menopausal women
‐Age(SD): E group 55.4(6.6), E‐T group 58.3(9.1)
‐Inclusion criteria:
1. A postmenopausal woman being on a stable dose of estrogen at least 3 months
‐Exclusion criteria:
1. Uncontrolled hypertension or hyperlipidemia
2. Use of medication known to affect lipids
3. Poorly controlled diabetes mellitus
4. Unstable angina or congestive heart failure, myocardial infarction within three months of study
5. Preexisting liver disease
6. Renal impairment
7. Hepatic adenoma
8. History of breast or uterine cancer
9. Gall bladder disease
10. History of thromboembolic events

Interventions

‐EE 1.25 mg once a day
‐EE 1.25 mg plus mT 2.5 mg once a day
‐Route:oral
‐Co‐intervention: no (a progestin was prescribed after the last study visit)

Outcomes

‐Relevant outcomes:
1. Sense of well being: the Quality of Life at Menopause Scale
2. Sexual functioning(by means of BISF‐W, SRS, and SIQ)
3. Lipid profile
4. Body composition: DEXA , anthropometry
‐Other outcomes:
1. Hormone measurements( total estrogen, estradiol, total testosterone and free testosterone, SHBG)
2. Strength testing
3. Safety data

Notes

‐Baseline equality: no statistically significant differences between the E and E‐T groups in age, race, surgical or natural menopause and weight. The E group seemed to have a healthier sexual function at baseline than the E‐T group
‐The author was contacted and kindly supplied some information, but there was still some information unanswered.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

High risk

One or more outcomes of interest in the review are reported incompletely

Free of other bias?

High risk

Baseline imbalance (sexual function)

Methods

‐Design: single‐blind randomised(C), parallel group
‐No of centres: single
‐Duration: 16 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 40(20 in each group)
‐No of participants completed and analysed: not stated
‐No of noncompliers and losses to follow up: not stated
‐Compliance assessment:
‐Source of funding: not stated

Participants

‐Location: United Kingdom
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: not stated
‐Characteristics: surgically and naturally menopausal women with loss of libido
‐Age (range): 46.9(33‐61) yr
‐Inclusion criteria:
1. Postmenopausal women with loss of libido and a regular sexual partner
2. No contraindication for HT
‐Exclusion criteria:
1. Gross primary marital disturbance or significant concurrent psychopathology or physical illness
2. Concurrent use of medication that might affect libido or interfere with the proposed HT

Interventions

‐oestradiol 50 mg
‐oestradiol 50 mg plus T 100 mg
‐Route: implant
‐Co‐intervention: women with an intact uterus were treated with cyclical norethisterone 5 mg orally for 7 days each month

Outcomes

‐Relevant outcomes:
1. Sexual function: self‐rating scales of sexual and marital satisfaction
2. Menopausal symptoms: menopausal symptoms scale (Greene 1976)

Notes

‐Baseline equality: not stated
‐The author could not be contacted.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Outcome assessment was blinded

Incomplete outcome data addressed?
All outcomes

Unclear risk

number analysed not stated

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Unclear risk

insufficient information

Methods

‐Design: double‐blind, randomised, placebo‐controlled, crossover study
‐No of centres: single
‐Duration: 24 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: yes
‐No of participants randomised: 36
‐No of participants completed the study: 33
‐No of participants analysed: 36
‐No of noncompliers and losses to follow up: 3 (one moved out of State, one; no change to her condition, one; lost to follow up)
‐Compliance assessment:`not stated
‐Source of funding:pharmacological company

Participants

‐Location: Australia
‐Setting: population‐based
‐Ethnicity: Caucasian
‐Run‐in period: 2 week run‐in with transdermal oestrogen
‐Characteristics: surgically and naturally menopausal women with loss of libido
‐Age (range): 46.9 (33‐61) yr
‐Inclusion criteria:
1. Hysterectomy
2. Decrease sexual motivation

3. In a stable relationship for at least 6 months

4. Normal thyroid function

5. Postmenopausal FSH level

‐Exclusion criteria:
1. Major illness
2. Taking antidepressants, steroid hormones

3. Severe depression

4. Dysfunctional relationship

5. Use of alternative therapy products which may influence hypoactive sexual desire disorder, mood, or energy

Interventions

Transdermal HT plus 1% testosterone cream (10 mg of testosterone, Andro‐Feme) versus transdermal HT plus placebo cream

Outcomes

Sexual function, mood, energy, lipid profile, discontinuation rate

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

No missing data

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: two
‐Duration: 2 4 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 31(14 in E group, 17 in E‐T group)
‐No of participants completed the study: 31/31=100%
‐No of participants analysed: 100% for lipoprotein levels at baseline, 2 months, and 6 months. 30/31=96.8% for lipoprotein at 4 months. 19/31=61.3% (10 in E group, 9 in E‐T group) for HDL subfraction
‐No of noncompliers and losses to follow up: 0/31 = 0%
‐Compliance assessment: not stated
‐Source of funding: not stated

Participants

‐Location: United Kingdom
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: no
‐Characteristics: surgically menopausal women with climacteric symptoms
‐Age(range): 46.4 (36‐54) yr
‐Inclusion criteria:
1. TAH with BSO for non‐malignant condition at least 6 weeks earlier
‐Exclusion criteria:
1. Receiving any hormone therapy prior to commencing treatment nor were taking any drug to interfere with lipid metabolism
2. Renal or hepatic abnormalities

Interventions

‐17 beta‐estradiol 50 mg
‐17 beta‐estradiol 50 mg plus T 100 mg
‐Route: implant
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Lipid profile
‐Other outcomes:
1. Hormone measurements

Notes

‐Baseline equality: not stated. However, baseline levels of lipid profiles were shown in the table and seemed to be similar in two groups.
‐ The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A‐Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

No missing data

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Unclear risk

insufficient information

Methods

See Floter 2002b

Participants

See Floter 2002b

Interventions

See Floter 2002b

Outcomes

See Floter 2002b

Notes

See Floter 2002b

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Floter 2002b

Allocation concealment?

Low risk

See Floter 2002b

Blinding?
All outcomes

Low risk

See Floter 2002b

Incomplete outcome data addressed?
All outcomes

High risk

See Floter 2002b

Free of selective reporting?

High risk

See Floter 2002b

Free of other bias?

High risk

See Floter 2002b

Methods

‐Design: double‐blind randomised (A), crossover study
‐No of centres: single
‐Duration: 24 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 50
‐No of participants completed/analysed: 44/50 = 88%(22 in E‐group, 22 in E‐T group at the end of phrase 2 of the study)
‐No of noncompliers: 6/50 = 12%. Reasons were poor drug compliance(5/50= 10%), and migraine during E‐P period(1/50=2%)
‐No of losses to follow up: 0%
‐Compliance assessment: not stated
‐Source of funding: partly funded by drug company

Participants

‐Location: Sweden
‐Setting: population‐based
‐Ethnicity: unspecified
‐Run‐in period: washout 2 months
‐Characteristics: healthy surgically menopausal women
‐Age (SD): 54 (2.9) yr
‐Inclusion criteria:
1. Age 45‐60 years
2. History of TAH with BSO for benign disease
3. BMI 18‐29 kg/m²
4. BP < 170 mmHg systolic and/or 105 mmHg diastolic
5. Normal mammogram within the past year
‐Exclusion criteria:
1. Previous use of HT(< past 2 months), other medication taken at the same time
2. History of or present pre malignancies, liver disease, cardiovascular, cerebrovascular or thromboembolic disorders
3. Present psychiatric disease
4. Regular use of tranquillizers and/or antihistamines
5. Alcohol abuse or smoking of at least 10 cigarettes/day

Interventions

‐oestradiol valerate 2mg once a day
‐oestradiol valerate 2mg plus testosterone undecanoate 40 mg once a day
‐Route: oral
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sense of well being: Psychological General Well Being Index
2. Sexual function: McCoy's sex scale questionnaire
3. Hirsutism and acne
4. Blood count
‐Other outcomes:
1. Self‐esteem: questionnaire concerning a woman's view of her own abilities in social life and work.
2. Other safety outcomes
3. Clitoral enlargement
4. Hormone measurements

Notes

‐Baseline equality: not applicable
‐Differences between treatment periods were assessed using Fisher's permutation test. No significant treatment‐by‐sequence group interaction, indicating no 'carry‐over effect'.
‐ The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

High risk

One or more outcomes of interest in the review are reported incompletely

Free of other bias?

High risk

Crossover trial, no washout period

Methods

See Floter 2002b

Participants

See Floter 2002b

Interventions

See Floter 2002b

Outcomes

See Floter 2002b

Notes

See Floter 2002b

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Floter 2002b

Allocation concealment?

Low risk

See Floter 2002b

Blinding?
All outcomes

Low risk

See Floter 2002b

Incomplete outcome data addressed?
All outcomes

High risk

See Floter 2002b

Free of selective reporting?

High risk

See Floter 2002b

Free of other bias?

High risk

See Floter 2002b

Methods

See Floter 2002b

Participants

See Floter 2002b

Interventions

See Floter 2002b

Outcomes

See Floter 2002b

Notes

See Floter 2002b

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Floter 2002b

Allocation concealment?

Low risk

See Floter 2002b

Blinding?
All outcomes

Low risk

See Floter 2002b

Incomplete outcome data addressed?
All outcomes

High risk

See Floter 2002b

Free of selective reporting?

High risk

See Floter 2002b

Free of other bias?

High risk

See Floter 2002b

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single
‐Duration: 24 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 26 (13 in each group)
‐No of participants completed and analysed: 26/26 =100%
‐No of noncompilers and losses to follow up: 0
‐Compliance assessment: subjects had to take at least 75% of their assigned medication for 4 consecutive weeks.
‐Source of funding:partly funded by drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: White
‐Run‐in period: not stated
‐Characteristics: healthy postmenopausal women, unclear type of menopause
‐Age:E group 50, E‐T group 52
‐Inclusion criteria:
1. Age 40‐60 years with no menstrual bleeding in the last 12 months
2. No history of steroid ingestion for 4 weeks, treatment with adrenergic agonists or antagonists, peripheral vasodilators, cholesterol‐lowering agents, beta‐blockers, beta‐mimetics or thyroid hormones
3. Nonsmokers or ex‐smokers who had not smoked in the past 12 months
‐Exclusion criteria:
1. History of genital tract disease
2. Current or previous estrogen‐dependent malignancy
3. History of jaundice or elevated liver enzyme
4. Gall bladder disease
5. history of cardiovascular disease
6. Current hypertriglyceridemia
7. Severe hypertension

Interventions

‐EE 0.625 mg once a day
‐EE 0.625 mg plus mT 1.25 mg once a day
‐Route: oral
‐Co‐intervention: not stated

Outcomes

‐Relevant outcomes:
1. Vasomotor and menopausal symptoms: fifteen symptoms were evaluated(hot flushes, cold sweats, vaginal dryness, cold hands and feet, breast pain or tenderness, numbness and tingling, skin crawls, edema, increased facial or body hair, voice deepening, acne, trouble sleeping, pounding of the heart, dizzy spells, and pressure or tightness in the head or body
2. Lipid profile
3. Red blood cell count
‐Other outcomes:
1. Endometrial histology
2. Vaginal pathology
3. Other safety clinical laboratory evaluations

Notes

‐Baseline equality: no statistically significant differences between the treatment groups with regard to age, time since menopause, the menopausal symptoms scale and lipid profiles.
‐The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

No missing data

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single centre
‐Duration: 24 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised:49 in E2/NETA,  50 in E2/NETA+testosterone

‐No of participants completed the study: not stated

‐Number of participants analysed: 41 in E2/NETA,  47 in E2/NETA+testosterone
‐No of noncompilers: 8 in E2/NETA,  3 in E2/NETA+T (discontinued treatment or not having FNA biopsy)
‐No of losses to follow up: not stated
‐Compliance assessment: not stated
‐Source of funding:the Swedish Cancer Society, the Swedish Research Council (project 5982), and the Karolinska Institutet Research Funds. The clinical trial with the testosterone patch was supported by an unrestricted grant from Procter & Gamble Pharmaceuticals, Egham Surrey, UK.

Participants

‐Characteristics: naturally menopausal women.
‐Age: 45‐65 years
‐Location: Sweden
‐Setting: unclear
‐Ethnicity: Caucasian
‐Run‐in period: no
‐Inclusion criteria:

1. postmenopausal for at least 12 months and had FSH > 40 IU/L

2. None of the women had taken any sex steroid hormones during the last 3 months before the study.

3. All the women had a normal mammogram within 1 month of entering the study.
‐Exclusion criteria:

1. Previous history of cancer or previous breast disease

2. An abnormal mammogram

3. Hypertension (systolic blood pressure >170 mm Hg or diastolic >105 mm Hg), hyperlipidaemia (total cholesterol 98.0 mmol/L or triglycerides 93.0 mmol/L), diabetes mellitus

4. History of thromboembolic disease, undiagnosed vaginal bleeding, any sign of hepatic dysfunction,

5. Concomitant treatment known to influence the study medication (warfarin, rifampicin, carbamazepine, griseofulvin, hydantoins, primidone, barbiturates, and broad‐spectrum antibiotics).

Interventions

17beta‐estradiol (E2) 2 mg and norethisterone acetate (NETA) 1 mg plus testosterone patch releasing 300 kg/24 hours versus 17beta‐estradiol (E2) 2 mg and norethisterone acetate (NETA) 1 mg plus placebo patch  

Outcomes

Breast cell proliferation, dense breast, and discontinuation rate

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: multicentre
‐Duration: 52 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: yes by default
‐No of participants randomised: 37 (21 in E group, 16 in E‐T group)
‐No of participants completed the study: 37
‐No of participants analysed: 37
‐No of non compilers: no
‐No of losses to follow up: no
‐Compliance assessment: not stated
‐Source of funding: not stated

Participants

‐Characteristics: hysterectomised postmenopausal women.
‐Age: E group 52.57+6.26, E‐T group 54.06+4.85
‐Location: Brazil
‐Setting: unclear
‐Ethnicity: White(31.25), Black(37.5), Mulatto(31.25)
‐Run‐in period: no
‐Inclusion criteria: with
1. < 65 year‐old
2. Undertaken Hysterectomy
3. Serum FSH in the menopausal range (>40mIU/ml)
‐Exclusion criteria:
1. Acne or hirsutism classified as greater than a Ferriman‐Galley score of 8
2. Impaired hepatic or renal function
3. Diabetes mellitus
4. Coronary disease
5. Systolic blood pressure > 180mmHg or diastolic blood pressure >110mmHg
6. use of any oestrogen formulation in the past 3 months
7. contraindications for oestrogen replacement

Interventions

‐ Estradiol gel 1mg/d plus methyltestosterone 1.25 mg/d
‐ Estradiol gel 1mg/d plus placebo
‐ Route: percutaneous oestrogen, oral T patch
‐ Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Body composition
2. Lipid
‐Other outcomes:
1. Blood pressure
2. Fibrinogen levels

Notes

‐Baseline equality: no statistically significant differences across treatment groups with regard to age, ethnicity, and age at menopause
‐The author was contacted. No further information was supplied.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

No missing data

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised(A), parallel group
‐No of centres: 20
‐Duration: 16 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 218(111 in E group, 107 in E‐T)
‐No of participants completed the study: 182/218 = 83.5%(87 in E‐T group, 95 in E)
‐No of participants analysed: 218
‐No of non compilers: 36/218= 16.5%(20 in E‐T group, 16 in E group). Reasons were adverse events(9 in E‐T, 5 in E), lack of efficacy(2 in E‐T, 3 in E), and administrative problem(9 in E‐T, 8 in E)
‐No. of losses to follow up: not stated
‐Compliance assessment: not stated
‐Source of funding:Not stated

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: White (91.8%), Black (4.6%), Hispanic (2.3%), other (1.3%)
‐Run‐in period: 2 weeks of receiving esterified oestrogen 0.625 mg per day
‐Characteristics: surgically and naturally menopausal women with hypoactive sexual desire associated with the onset of menopause
‐Age(SD):E group 53.8(5.7), E‐T group 52.9(5.7)
‐Inclusion criteria:
1. Healthy postmenopausal women(natural or surgical for at least 6 months)
2. Age 45‐65 years
3. Hypoactive sexual interest or desire associated with the onset of menopause
4. No overt mood disorders
5. A history of adequate sexual interest before the onset of menopause
6. Receiving the equivalent of 0.625 mg of conjugated equine estrogens for 3 or more months
7. A stable, monogamous, heterosexual relationship
‐Exclusion criteria:
1. Dyspareunia
2. Unresolved or recent sexual abuse
3. Depressive or anxiety symptoms or physical limitations that interfered with normal sexual functioning
4. An abnormal mammogram
5. Recent clinical laboratory test abnormalities
6. Recent previous high dose oestrogen therapy or other sex hormones, lipid‐lowering agents, antidepressants(including selective serotonin‐reuptake inhibitors), anxiolytics, thyroid replacement medication(unless a stable dose), or antihypertensive drug.
4.

Interventions

‐EE 0.625 mg once a day
‐EE 0.625 mg plus mT 1.25 mg once a day
‐Route:oral
‐Co‐intervention: no (a progestin was prescribed after the last study visit)

Outcomes

‐Relevant outcomes:
1. Sexual function: SIQ and BISF‐W
2. Lipid profile
3. Hirsutism:the scale of Lorenzo
4. Acne:the scale of Palatsi

Notes

‐Baseline equality: Two groups were similar in terms of age, BMI, race, time since menopause, type of menopause, marital status, percent of highest educational level, total and bioavailable testosterone.
‐ The author was contacted and kindly provided further information.
‐The baseline sexual dimension scores, lipid profiles, hirsutism score and acne score seemed to be similar in the two groups.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

See Miller 2000

Participants

See Miller 2000

Interventions

See Miller 2000

Outcomes

See Miller 2000

Notes

See Miller 2000

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Miller 2000

Allocation concealment?

Low risk

See Miller 2000

Blinding?
All outcomes

Low risk

See Miller 2000

Incomplete outcome data addressed?
All outcomes

High risk

See Miller 2000

Free of selective reporting?

High risk

See Miller 2000

Free of other bias?

Unclear risk

See Miller 2000

Methods

See Miller 2000

Participants

See Miller 2000

Interventions

See Miller 2000

Outcomes

See Miller 2000

Notes

See Miller 2000

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Miller 2000

Allocation concealment?

Low risk

See Miller 2000

Blinding?
All outcomes

Low risk

See Miller 2000

Incomplete outcome data addressed?
All outcomes

High risk

See Miller 2000

Free of selective reporting?

High risk

See Miller 2000

Free of other bias?

Unclear risk

See Miller 2000

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single centre
‐Duration: 8 weeks
‐Power calculation: no
‐Intention‐to‐treat analysis: no
‐No. of participants randomised: Estratab 18; Estratab‐Provera 18; Estratab‐micronized progesterone 17; Estratest(combination oestrogen and androgen) 20; Placebo 16
‐No. of participants completed the study: Estratab 16; Estratab‐Provera 18; Estratab‐micronized progesterone 16; Estratest 19; Placebo 16
‐No. of participants analysed: unclear
‐No. of non compilers: unclear
‐No of losses to follow up: Estratab 2, Estratab‐Provera 1, Estratab‐micronized progesterone 1, Estratest 1
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: healthy postmenopausal women
‐Age: mean (SEM) Placebo 57.0 (0.94), Estratab 57.0 (1.1), Estratab‐Provera 57.5 (0.90), Estratab‐micronized progesterone 56.0 (0.89), Estratest 56.7 (0.79) yr
‐Location: US
‐Setting: population‐based
‐Ethnicity: 80 Caucasians, 8 African Americans, 1 other
‐Run‐in period: no
‐Inclusion criteria:
1. 48‐65 year‐old
2. Menopause
‐Exclusion criteria:
1. BW >30% than ideal body weight as determined by Metropolitan Life Tables
2. History of medication‐dependent diabetes, heart disease, pulmonary embolism or deep vein thrombosis, liver or pancreatic disease, and hypertension
3. Use of lipid lowering drugs, and daily use of steroids, current use of medications that would affect cardiovascular function
4. Unwillingness to not smoke for 12 hr prior to testing
6. Having a menstrual period or any unexplained vaginal bleeding for 12 months prior to the study,
7. Use of hormone therapy in the 3 months
8. Contraindications for hormone therapy
9. An abnormal pap smear
10. Fasting serum triglyceride levels >250 mg/dl

Interventions

‐Oral Estratab (1.25 mg/day) and placebo pill; Estratab (1.25 mg/day) and Provera continuous (5 mg); Estratab (1.25 mg/day) and Prometrium, micronized progesterone (100 mg/day); Estratest, combination oestrogen and androgen, and placebo pill; and two placebo pills
‐Route: oral
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sense of well being
‐Other outcomes:
1. Cardiovascular response to stress

Notes

‐Baseline equality: no significant differences across treatment groups with regard to age, years of education, race, marital status, highest educational degree attained, current occupational status, family income, or family history of high blood pressure, diabetes, angina, myocardial infarction, other heart disease, stroke or cancer, baseline blood pressure or heart rate
‐The author was contacted and kindly provided the further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Unclear risk

Insufficient information

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single
‐Duration: 12 months
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 66
‐No of participants completed the study: 57/66 = 86.4% (30 in HT group, 27 in HT‐T)
‐No of participants analysed: 57
‐No of noncompliers: 9/66 = 13.6%. Reasons were breakthrough uterine bleeding(3), skin rash/acne(2), weight gain(2), PMS symptoms(1), other illness(1)
‐No of losses to follow up: 0%
‐Compliance assessment: not stated
‐Source of funding:partly funded by drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: not stated
‐Characteristics: healthy surgically and naturally menopausal women
‐Age (SEM): E group 53.5(1), E‐T group 54.6(1.2) yr
‐Inclusion criteria:
1. Postmenopausal women with no contraindications to HT
‐Exclusion criteria:
1. Patients who had taken any drug known to alter calcium or bone metabolism

Interventions

Patients with hysterectomy
‐micronised oestradiol 0.5 mg twice a day
‐micronised oestradiol 0.5 mg twice a day plus micronised testosterone 1.25 mg twice a day
Patients with intact uterus
‐micronised oestradiol 0.5 mg twice a day plus micronised progesterone 100 mg
‐micronised oestradiol 0.5 mg twice a day plus micronised progesterone 100 mg plus micronised testosterone 1.25 mg twice a day
‐Route: sublingual
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Biochemical markers of bone metabolism;
1.1. Urinary markers: Dpd and NTx
1.2. Serum marker: BSAP
2. BMD of lumbar spines and hip: DEXA
‐Other outcomes:
1. Hormone measurements

Notes

‐Baseline equality: no differences in age, height, weight, oestradiol and FSH levels, biochemical markers levels and BMD between the two groups.
‐The corresponding author was contacted and kindly supplied information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

High risk

One or more outcomes of interest in the review are reported incompletely

Free of other bias?

Unclear risk

insufficient information

Methods

‐Design: double‐blind randomised (C), parallel group
‐No of centres: single
‐Duration: 16 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 84 (29 in P group, 28 in E group, 27 in E‐T)
‐No of participants completed the study: 70 (21 in P group, 25 in E, 24 in E‐T)
‐No of participants analysed: 70
‐No of noncompliers: 14/84 = 16.7%. Reasons: 1 acute cholecystitis (E group), 1 attempted suicide (E‐T group), 6 symptoms not alleviated (P group), 6 lost to follow up (3 in P group, 2 in E‐T group, 1 in E group)
‐No. of losses to follow up: 6/84=7.1%.
‐Compliance assessment: not stated
‐Source of funding: not stated

Participants

‐Location: United Kingdom
‐Setting: unclear
‐Ethnicity: unspecified
‐Run‐in period: not stated
‐Characteristics: perimenopausal, surgically and naturally menopausal women with menopausal symptoms
‐Age: E group 46, E‐T group 50, P group 48
‐Inclusion criteria:
1. The same as stated in disease status
‐Exclusion criteria:
1. Women with a contraindication to estrogen therapy

Interventions

‐estradiol 50 mg
‐estradiol 50 mg plus T 100 mg
‐placebo
‐Route:implant
‐Co‐intervention:

Outcomes

‐Relevant outcomes:
1. Psychiatric symptoms: the short version of Kellner and Sheffield's self rating scale of distress(SRD 30)

Notes

‐Baseline equality: no differences between the three groups in age, menopausal status, or the presence of a uterus.
‐The study was designed to last for 6 months but many women withdrew after 4 months because they felt that the effects of the implant were wearing off.
‐ The author could not be contacted.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

High risk

One or more outcomes of interest in the review (sense of well being) are reported incompletely.

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (A), crossover study
‐No of centres: single centre
‐Duration: 24 (12/12) weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 60
‐No of participants completed the study: 53
‐No of participants analysed: 53
‐No of noncompliers: 4 did not comply to medication, 1 had a fracture, 1 developed a skin disease, 1 had a carcinoma of the uterus
‐No of losses to follow up: no
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: postmenopausal women with menopausal onset of low sexual desire with low serum T levels
‐Age: mean+SD 55.4+3.5 yr
‐Location: Sweden
‐Setting: unclear
‐Ethnicity: unclear
‐Run‐in period: not stated
‐Inclusion criteria:
1. Postmenopausal women
2. Age 50‐65 year‐old
3. Generally good health
4. Complaining of total loss or significant decrease of libido during the postmenopausal period
5. Serum free‐T < 2nmol/l at baseline
7. Stable estrogen dose > 3 months
8. Menopause onset of low sexual desire
‐Exclusion criteria:
1. Having a partner
2. Experience of previous androgen therapy
3. Medications known to affect sexual function
4. Heart disease, high blood pressure, malignant disease or other serious chronic disease

Interventions

‐Percutanous treatment with testosterone gel 10 mg/d‐hormone therapy
‐Placebo gel‐hormone therapy
‐Route: percutaneous testosterone gel
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function
2. Sense of well being
3. Lipid profile
4. Hirsutism
5. Acne
6. Hematocrit
‐Other outcomes:
1. Skin‐related side effect

Notes

‐Baseline equality: not applicable
‐Conference proceeding.
‐The author was contacted and kindly provided the further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Crossover trial, no washout period

Methods

See Dobs 2002

Participants

See Dobs 2002

Interventions

See Dobs 2002

Outcomes

See Dobs 2002

Notes

See Dobs 2002

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Dobs 2002

Allocation concealment?

Low risk

See Dobs 2002

Blinding?
All outcomes

Low risk

See Dobs 2002

Incomplete outcome data addressed?
All outcomes

Low risk

See Dobs 2002

Free of selective reporting?

High risk

See Dobs 2002

Free of other bias?

High risk

See Dobs 2002

Methods

‐Design: open randomised (A), parallel group
‐No of centres: single
‐Duration: 8 months
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 40
‐No of participants completed the study: 33/40 = 82.5% (18 in E group, 15 in E‐T group)
‐No of participants analysed: not stated
‐No of non compilers: 7/40 = 17.5%. Reasons were having signs of hyperandrogenism(3 in E‐T), on the advice of their general practitioners(2 in E‐T), personal reasons(1 in E) and subsequent diagnosis of lymphoma(1 in E)
‐No of losses to follow up: 0 =0%
‐Compliance assessment: not stated
‐Source of funding: not stated

Participants

‐Location: Italy
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: no
‐Characteristics: healthy naturally menopausal women
‐Age: E group 55.3, E‐T group 57.4 yr
‐Inclusion criteria:
1. postmenopausal women already on HT at least 1 year
‐Exclusion criteria:
1. Major disease(Hypertension, heart disease, diabetes, renal or peripheral vascular diseases
2. surgical removal of uterus or ovaries

Interventions

‐oestradiol 50 micrograms once a day plus MPA 10 mg/d for a duration of 2 weeks every two months
‐oestradiol 50 micrograms once a day plus MPA 10 mg/d for a duration of 2 weeks every two months plus testosterone undecanoate 40 mg once a day
‐Route: transdermal oestradiol, oral progestin, oral testosterone
‐Co‐intervention: not stated

Outcomes

‐Relevant outcomes:
1. Psychological well being: a 10‐cm VAS
2. Sexual desire and satisfaction: a 10‐cm VAS
3. Lipid profile
‐Other outcomes:
1. Pulsatility index of internal carotid artery and middle cerebral artery (primary outcome)
2. Endometrial thickness
3. Testosterone levels

Notes

‐Baseline equality: no statistically significant differences between the two groups in terms of age, BMI, years of menopause, duration of HT, sexual desire and satisfaction scores.
‐ The author was contacted and kindly supplied further information, but there was no data available (psychological well being, sexual function) for inclusion in the meta‐analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

High risk

Open randomised trial

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

High risk

One or more outcomes of interest in the review (sense of well being) are reported incompletely

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single
‐Duration: 52 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 60
‐No of participants completed/analysed: 56
‐No of non compilers: 2 in HT had abnormal uterine bleeding, 2 in HT+T fear of hormonal treatment
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Location: Sao Paulo Brazil
‐Setting: hospital‐based
‐Ethnicity: 40 women in the group (66.7%) were Caucasian and 20 (33.3%) Afro‐Brazilian.

‐Run‐in period: no
‐Characteristics: naturally menopausal women with sexual problem after menopause
‐Age: 42 ‐ 60 years
‐Inclusion criteria:
1. amenorrhoea for a minimum of 1 year 2. an intact uterus 3. a stable relationship with a partner capable of intercourse 4. appearance of sexual complaints after menopause.

‐Exclusion criteria:
1. hormone therapy 2. systemic diseases, endocrine and psychiatric illnesses 3. severe genital dystopia

Interventions

‐ Treatment: mMethyltestosterone 2 mg/day combined with HRT (conjugated equine estrogens 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day)

‐ Control/Placebo: HRT (conjugated equine oestrogens 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day

‐Route: oral

‐Co‐intervention: no

Outcomes

Sexual function and discontinuation rate

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Unclear risk

insufficient information

Methods

‐Design: open randomised (C), parallel group
‐No of centres: three
‐Duration: 6 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 28
‐No of participants analysed: 26
‐No of noncompliers and losses to follow up: not stated
‐Compliance: not stated
‐Source of funding:partly funded by drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: 3 weeks of receiving calcium intake 1000‐1500 mg per day by dietary adjustments or addition of calcium supplement
‐Characteristics: healthy surgically and naturally menopausal women
‐Age(range): E group 65.7(49.1‐80.4), E‐T group 59.8(46.6‐78.5)
‐Inclusion criteria:
1. The same as stated in disease status
2. BMI within 25% of ideal body weight
3. Nonsmokers
4. Not taken estrogens within the last 6 months
5. No prior history of oestrogen‐dependent cancer, hypercortisolism, hyperthyroidism, or metabolic bone disease
6. A negative mammogram and Pap smear within one year and normal ECG
‐Exclusion criteria:
1. Any prior treatment with drugs that might affect bone metabolism, other than calcium supplements and estrogens, or with drug known to alter hepatic enzymes

Interventions

‐CEE 1.25 mg once a day
‐EE 1.25 mg plus mT 2.5 mg once a day
‐Route:oral
‐Co‐intervention:no

Outcomes

‐Relevant outcomes:
1. Menopausal symptoms: a modified menopausal index with a 0‐3 scale
2. Bone formation markers (serum OC, BSAP, PICP) and bone resorption markers(pyridinoline, Dpd and hydroxyproline)
3. Lipid profile
‐Other outcomes:
1. Hormone measurement (oestrone, oestradiol, testosterone, DHT, SHBG, intact PTH, 25‐hydroxy vitamin D
2. Adverse event (headache, breast pain, acne, vaginal bleeding)
‐Time points: 3, 6, 9 weeks

Notes

‐Baseline equality: no significant differences in weight, height, BMD, menopause duration, oophorectomy status and prior HT duration between two groups. The E‐T group was somewhat younger than the E group. There were no differences in general biochemical profiles or haematological measures.
‐The author was contacted, but the further information could not be provided.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C‐Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

High risk

Open randomised trial

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

High risk

One or more outcomes of interest in the review are reported incompletely.

Free of other bias?

High risk

Baseline imbalance (menopausal symptom score, age)

Methods

‐Design: double‐blind randomised(A), crossover study
‐No of centres: single
‐Duration: 16 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: not stated (assumed 42)
‐No of participants completed the study: not stated (35/42 = 83.3% had complete data set)
‐No of participants analysed: depended on outcomes
‐No of noncompliers: Reasons were unprecedented anxiety(1), poor feeling(1), and using Estring(1)
‐No of losses to follow up: no
‐Compliance assessment: a pill count was recorded to estimate treatment compliance.
‐Source of funding: drug company

Participants

‐Location: United States
‐Setting: population‐based
‐Ethnicity: unspecified
‐Run‐in period: no
‐Characteristics: healthy surgically and naturally menopausal women
‐Age(range): 55.5 (38‐65) yr
‐Inclusion criteria:
1. Natural or surgical menopause
2. Currently use HT
3. No prior androgen replacement therapy, psychotropic drugs and no major systemic disease
4. Used no more than three caffeinated drinks per day, two alcohol drinks per week, ten cigarette per day
5. BMI below 29
‐Exclusion criteria:not stated

Interventions

‐EE 0.625 mg once a day
‐EE 0.625 mg plus mT 1.25 mg once a day
‐Route:oral
‐Co‐intervention: not stated

Outcomes

‐Relevant outcomes:
1. Libido: an 80‐mm VAS
2. Sexual enjoyment: a scale of 0‐3
3. Anxiety: the State‐Trait Anxiety Inventory, depression by the Zung Self‐Rated Depression Inventory, somatization by the symptom Check List‐90 Revised, and playfulness in the subjects' self‐image by the Adult Playfulness Scale.
4. Menopausal symptoms: the Menopause‐specific Quality of Life Questionnaire(MENQOL)
4. Neurobehavioral outcomes: computerized test
5. Complex verbal and associated fluency: the Possible Jobs and Alternate Uses measures
‐Other outcomes:
1. Subjective sleep quality
2. Exercise levels

Notes

‐Baseline equality: not applicable
‐The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Cross‐over trial, no washout period

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: single
‐Duration: 8 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised: 20 (10 in E‐T, 10 in E)
‐No of participants completed/analysed: 19
‐No of noncompliers: 1 in E
‐No of losses to follow up: 1 in E
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: predominantly Caucasian
‐Run‐in period: 2 weeks of receiving previous estrogens and then 2 weeks of placebo
‐Characteristics: surgically and naturally menopausal women dissatisfied with their concurrent treatment at least 4 months
‐Age (range): 52 (45‐55) yr
‐Inclusion criteria:
1. As stated in disease status
2. Inadequate symptomatic relief included hot flashes, vaginal dryness, dyspareunia, decreased libido and decreased energy levels
3. BW above or below 25% of ideal BW
‐Exclusion criteria:
1. Clinically significant abnormal cervical cytology smear
2. Clinically significant abnormal mammograms within the past 12 months or clinically significant abnormal finding during pelvic examination
3. History of thromboembolic disorder or active thromboembolic disease in the past 12 months
4. Active or previous estrogen‐dependent breast, uterine or ovarian cancer, as well as undiagnosed uterine or vaginal bleeding at examination or in the past year

Interventions

‐EE 1.25 mg once a day
‐EE 1.25 mg plus mT 2.5 mg once a day
‐Route:oral
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual behavior and enjoyment: the 10‐item Sexual Activity and Libido Scale
2. Menopausal symptoms: the Menopausal Symptom Scale (modified from the original scale developed by Kupperman et al.)
‐Other outcomes:
1. Vaginal smear maturation index
2. Hormone measurements

Notes

‐Baseline equality: not stated
‐The author was contacted and kindly provided further information; however, the menopausal symptom and quality of life data to enable to meta‐analysis was no longer retrievable.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

High risk

One or more outcomes of interest in the review (menopausal symptoms) are reported incompletely

Free of other bias?

Unclear risk

insufficient information

Methods

‐Design: double‐blind randomised (C), parallel group
‐No of centres: two
‐Duration: 12 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 30 ‐No. of participants completed/analysed: 24/30=80%
‐No of noncompliers: 6/30 = 20%. Reasons were not stated.
‐No of losses to follow up: not stated
‐Compliance assessment: not stated
‐Source of funding: drug company provided medication

Participants

‐Location: United States
‐Setting: population‐based
‐Ethnicity: Caucasian 83.3% (14/24), Black African American 12.5% (3/24), Other 4.2% (1/24)
‐Run‐in period: 30 days of placebo
‐Characteristics: healthy surgically menopausal women
‐Age (SD): E 53.74 (3.85), E‐T 54.56 (5.13) yr
‐Inclusion criteria: the participants had to ‐
1. TAH with BSO
2. not be taking any prescription medications
3. have estimated IQ. of at least 80 based on the Symbol Digit Modalities Test
4. be a high school graduate or have an equivalent degree
‐Exclusion criteria:
1. A history of head injury with loss of consciousness greater than 30 minutes
2. a history of alcohol or drug abuse
3. any current Axis I psychotic level disorder
4. a history of central nervous system infection
5. a history of serious concurrent acute or chronic diseases of a severity to negatively impact cognitive ability
6. current use of medications known to adversely affect cognitive function
7. a learning disability
8. a first language other than English

Interventions

‐EE 0.625 mg once a day
‐EE 0.625 mg plus mT 1.25 mg once a day
‐Route:oral
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual desire
2. Cognition: Symbol Digits Modality Test

Notes

‐Baseline equality:Both groups had comparable demographics for personal characteristics (age, height, weight, length of menopause), group characteristics (education, race) and basic intelligence (as measured by the screening test, the Symbol Digit Modalities Test).
‐The author could not be contacted.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

See Sherwin 1988

Participants

See Sherwin 1988

Interventions

See Sherwin 1988

Outcomes

See Sherwin 1988

Notes

See Sherwin 1988

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Sherwin 1988

Allocation concealment?

Low risk

See Sherwin 1988

Blinding?
All outcomes

Low risk

See Sherwin 1988

Incomplete outcome data addressed?
All outcomes

High risk

See Sherwin 1988

Free of selective reporting?

High risk

See Sherwin 1988

Free of other bias?

Low risk

See Sherwin 1988

Methods

See Sherwin 1988

Participants

See Sherwin 1988

Interventions

See Sherwin 1988

Outcomes

See Sherwin 1988

Notes

See Sherwin 1988

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Sherwin 1988

Allocation concealment?

Low risk

See Sherwin 1988

Blinding?
All outcomes

Low risk

See Sherwin 1988

Incomplete outcome data addressed?
All outcomes

High risk

See Sherwin 1988

Free of selective reporting?

High risk

See Sherwin 1988

Free of other bias?

Low risk

See Sherwin 1988

Methods

See Sherwin 1988

Participants

See Sherwin 1988

Interventions

See Sherwin 1988

Outcomes

See Sherwin 1988

Notes

See Sherwin 1988

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Sherwin 1988

Allocation concealment?

Low risk

See Sherwin 1988

Blinding?
All outcomes

Low risk

See Sherwin 1988

Incomplete outcome data addressed?
All outcomes

High risk

See Sherwin 1988

Free of selective reporting?

High risk

See Sherwin 1988

Free of other bias?

Low risk

See Sherwin 1988

Methods

‐Design: double‐blind randomised (A), crossover study
‐No of centres: single
‐Duration: 4 months (1 month of placebo and then 3 months of intervention)
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 49
‐No of participants completed/analysed: 40 (10 in each treatment group)
‐No of noncompliers: 9/49 = 18.4% Reasons were unable to take time off from work for testing sessions and unwilling to comply with testing procedure for the entire course of the study.
‐No of losses to follow up: no
‐Compliance assessment: no
‐Source of funding: not stated

Participants

‐Location: Canada
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: no
‐Characteristics: healthy surgically menopausal women
‐Age: 45.4 for TAH with BSO, 36.6 for TAH
‐Inclusion criteria:
1. Women needed to undergo TAH with BSO for benign condition
2. In a state of good general health
3. No known contraindications to HT
4. They had completed at least nine years of formal education
‐Exclusion criteria:
1. Past or current psychological disturbance

Interventions

‐estradiol valerate 10 mg
‐testosterone enanthate benzilic acid hydrozone 200 mg
‐estradiol dienanthate 7.5 mg plus estradiol benzoate 1 mg testosterone enanthate benzilic acid hydrozone 150 mg
‐placebo
‐no treatment (TAH patients)
‐Route:intramuscular injection
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Cognitive function(short and long‐term memory): digit span, clerical Speed and Accuracy and the Abstract Reasoning Subtest of the Differential Aptitude Test

Notes

‐Baseline equality: not applicable
‐ The author was contacted and kindly supplied further information, but there was no longer data to enable inclusion in the meta‐analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size

Free of selective reporting?

High risk

One or more outcomes of interest in the review are reported incompletely.

Free of other bias?

Low risk

Possibly free of other sources of bias

Methods

‐Design: double‐blind randomised (A), crossover study
‐No of centres: nine
‐Duration: 12 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 75
‐No of participants completed/analysed: 65/75=86.7%
‐No of noncompliers: 18/75 = 24% Reason were adverse events (3 while receiving placebo, 1 while receiving T150, 2 while receiving T300), poor compliance with the telephone diary(6), or personal reasons(6)
‐No of losses to follow up: 0%
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: White (83%), Black (11%), Hispanic (5%), Asian (1%)
‐Run‐in period: no
‐Characteristics: surgically menopausal women with impaired sexual function, low T levels and receiving adequate dose of estrogen therapy
‐Age (range): 47 (31‐56) yr
‐Inclusion criteria:
1. Healthy surgically menopausal women with TAH at least 1 year but less than 10 year with impaired sexual function, free T concentration less than 3.5 pg/ml or serum T concentrations < 30 ng/dl and received conjugated equine estrogen at least 0.625 mg/day at least 2 months
2. A stable, monogamous, heterosexual relationship for at least 1 year
3. BMI between 19.5‐33.5
‐Exclusion criteria:
1. Use of oral, topical, or vaginal androgen therapy in the previous three months or injectable or implantable androgen therapy in the previous 6 months
2. More than 20 moderate or severe hot flashes per week
3. Severe acne(grade 3 on the scale of Palatsi et al)
4. Moderate or severe hirsutism(score of 6 or more on the scale of Lorenzo)
5. Hyperlipidemia
6. Psychiatric disease
7. Dyspareunia
8. Physical limitations that interfered with normal sexual functioning
9. Use of glucocorticoids, selective serotonin‐reuptake inhibitors, tricyclic antidepressants, antiandrogen agents, gingseng, yohimbine, phytoestrogens, dehydroepiandrosterone, or melatonin

Interventions

‐CEE 0.625 mg once a day
‐CEE 0.625 mg once a day plus T 150 micrograms twice a week
‐CEE 0.625 mg once a day plus T 300 micrograms twice a week
‐Route:oral estrogen, transdermal patch testosterone
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function: the Brief Index of Sexual Functioning for Women
2. Mood: the Psychological General Well‐Being Index
3. Hirsutism: the scale of Lorenzo and facial‐deplication rate
4. Acne: the scale of Palatsi et al.
5. lipid profile
6. Blood counts
‐Other outcomes:
1. Hormone measurements (free testosterone, bioavailable testosterone, total testosterone, dihydrotestosterone and SHBG)
2. Other safety outcomes(fasting glucose concentrations, serum insulin concentrations, indicators of liver function, tolerance of the skin to transdermal systems and other adverse events
‐Time points:4, 8 and 12 weeks

Notes

‐Baseline equality: not applicable
‐ The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

High risk

Discontinuation >10%

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Cross‐over trial, no washout period

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: multicentre
‐Duration: 24 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: no
‐No of participants randomised: 549 (273 in E group, 276 in E‐T)
‐No of participants completed the study: E group 209/273 (76.6%), E‐T 224/276 (81.2%)
‐No of participants analysed: 539
‐No of non compilers: E group 59 (21.6%). Reasons were adverse event 19 (7.0%), voluntary 32 (11.7%), protocol violation 8 (2.9%) E‐T 46 (16.7%). Reasons were adverse event 22(8%), voluntary 19(6.9%), protocol violation 5(1.8%)
‐No of losses to follow up: E group 5/273 (1.8%), E‐T 6/276 (2.2%)
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: postmenopausal women with menopausal onset of low sexual desire with low serum T levels
‐Age: E group 54+4.95, E‐T 53.9+4.79 yr
‐Location: USA, Canada, Australia
‐Setting: population‐based
‐Ethnicity: White 256(94), 260(94) black 8(3), 10(4) Hispanic
‐Run‐in period: 8‐week pretreatment baseline period
‐Inclusion criteria:
1. 40‐70 year‐old
2. Cessation of menstruation > 1 year
3. Generally good health
4. Stable monogamous relationship with a partner > 1 year
5. Partner present more than 50% of the time
6. Stable oestrogen dose > 3 months
8. Hypoactive sexual desire disorder
‐Exclusion criteria:
1. Recent androgen use
2. Positive screening for depression or hypothyroidism
3. Ongoing medical, psychiatric or relationship disturbance
4. Medications known to affect sexual function
5. Severe hyperlipidaemia/metabolic disorders
6. Dyspareunia, physical limitations affecting sexual function

Interventions

‐A stable dose of oral oestrogen with or without progestin plus T 300 microgram/d
‐A stable dose of oral oestrogen with or without progestin plus placebo
‐Route:oral oestrogen, transdermal T patch
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function: SAL and PFSF
2. Hirsutism
3. Acne
‐Other outcomes:
1. Clitoromegaly, deepening of voice

Notes

‐Baseline equality: no significant differences across treatment groups with regard to age, ethnicity, BMI, duration of relationship, hysterectomy status, years since last menstrual period (non hysterectomy), SHBG and type of hormone therapy
‐The author was contacted and kindly provided the further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (C), parallel group
‐No of centres: three
‐Duration: 12 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: not stated
‐No of participants randomised:93
‐No of participants completed the study: 89/93 = 95.7%
‐No of participants analysed: not stated
‐No of non compilers: 3/93 = 3.2% All was assigned to E‐T(high) group. Reasons were an adverse event(rash) and two of relocation and subsequently lost to follow up
‐No of losses to follow up: 2/92 = 2.2%
‐Compliance assessment: stated only "compliance and protocol adherence were excellent".
‐Source of funding: not stated

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: unspecified
‐Run‐in period: 4 weeks of placebo treatment
‐Characteristics: healthy peri‐and postmenopausal women
‐Age (SE): E (low dose) group 54.5 (1.2), E‐T (low dose) group 52.0 (0.9), E (high dose) group 53.7 (0.9), E‐T (high dose) group 54.3 (1.2)
‐Inclusion criteria:
1. Naturally menopausal women with both ovaries intact
2. Nonsmokers
3. BW within 25% of ideal BW
4. A stable heterosexual relationships of at least 1 year duration
‐Exclusion criteria:
1. Use of estrogens, progestins, androgens, or anabolic steroids within 8 weeks of enrolment
2. No contraindication for HT

Interventions

‐EE 0.625 mg once a day
‐EE 1.25 mg once a day
‐EE 0.625 mg plus mT 1.25 mg once a day
‐EE 1.25 mg plus mT 2.5 mg once a day
‐Route:oral
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Menopausal symptoms: the scale of Kupperman et al.
‐Other outcomes:
1. Vaginal bleeding
2. Safety
2. Hormone measurements(estradiol, estrone, testosterone, dihydrotestosterone, androstenedione, DHEAS, SHBG
‐Time points: 4, 8, and 12 weeks

Notes

‐Baseline equality: patient characteristics were shown in table and they seemed to be similar in all groups in terms of age, BMI, duration of menopause and number of patients completing double‐blind phase.
‐The author could not be contacted.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Discontinuation rate <10%

Free of selective reporting?

High risk

One or more outcomes of interest in the review (menopausal symptoms) are reported incompletely

Free of other bias?

Unclear risk

insufficient information

Methods

‐Design: double‐blind randomised (A), parallel group
‐No of centres: multicentre
‐Duration: 24 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: available case analysis
‐No of participants randomised: 562 (E group 279, E‐T group 283)
‐No of participants completed the study: E group 230/279 (82%), E‐T group 221/283 (78%)
‐No of participants analysed: depended on outcome
‐No of noncompliers: E group 39(12%). The reasons were adverse events 19 (6.8%), protocol violation 3(1.1%), voluntary withdrawal 12(4.3%), investigator recommendation 5(1.8%). E‐T group 54(19.2%). The reasons were adverse events 24(8.5%), protocol violation 3(1.1%), voluntary withdrawal 26(9.2%), investigator recommendation 1(0.4%).
‐No of losses to follow up: 18 [E group 10 (3.6%); E‐T group 8 (2.8%)]
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: surgically menopausal women with menopausal onset of low sexual desire
‐Age: E group 48.9+7.4, E‐T group 49.2+7.7 49 yr
‐Location: US, Canada, Australia
‐Setting: population‐based
‐Ethnicity: E group Caucasian 242 (87%) Black 27 (10%) Hispanic 8 (3%) Other 2 (1%); E‐T group Caucasian 257 (91%), Black 19 (7%), Hispanic7 (2%), Other 0 (0%)
‐Run‐in period: 8‐week pretreatment baseline period
‐Inclusion criteria:
1. 20‐70 year‐old
2. Generally good health (normal mammogram if age > 40 yr, normal Pap smear, no
physical impediment to sexual function)
3. BMI 18‐30 kg/m2
4. TAH with BSO at least 6 months
5. Stable relationship with partner
6. Stable oestrogen dose > 3 months
7. Menopause onset of low sexual desire
‐Exclusion criteria:.
1. Drug or alcohol dependency
2. Recent androgen use
3. Hirsutism, virilization, severe acne
4. Positive screening for depression or hypothyroidism
5. Ongoing medical, psychiatric or relationship disturbance
6. Medications known to affect sexual function
7. Severe hyperlipidaemia/metabolic disorders
8. Dyspareunia, physical limitations affecting sexual function
9. Major life change interfering with sexual function
10. History of breast cancer or estrogen‐dependent neoplasia, significant organic disease that could affect the outcome of the study, active gall bladder disease, diabetes, history of cerebrovascular disease or thromboembolic disorders, or abnormal
levels of TSH, serum creatinine, or liver enzymes

Interventions

‐Oestrogen plus T 300 microgram/d
‐Oestrogen plus placebo
‐Route: oral or transdermal oestrogen, transdermal T patch
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function
2. Hirsutism
3. Acne
‐Other outcomes:
1. Alopecia
2. Deepening of voice

Notes

‐Baseline equality: no significant differences across treatment groups with regard to age, weight, height, BMI, ethnicity, route of administration of concomitant oestrogen, duration of relationship, years since oophorectomy, number of satisfying sexual episodes over 4 weeks, score on sexual desire domain, score on PDS
‐The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias

Methods

‐Design: double‐blind randomised (C), parallel group
‐No of centres: multicentre
‐Duration: 8 weeks
‐Power calculation: yes
‐Intention‐to‐treat analysis: available case analysis
‐No of participants randomised: 102 (50 in E group, 52 in E‐T group)
‐No of participants completed the study: E group 43/50 (86%), E‐T group 44/50 (81%)
‐No of participants analysed: 100
‐No of non compilers: E group 5. The reasons were adverse event 1, protocol violation 2, and other 2; E‐T group 7. The reasons were adverse event 5, protocol violation 1, and ineffectiveness 1.
‐No of losses to follow up: E group 2, E‐T group 0
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: surgically menopausal women with menopausal onset of low sexual desire
‐Age: E group 49.6 ? 6.6, E‐T group 48.1 ? 7.6 yr
‐Location: US
‐Setting: unclear
‐Ethnicity: E group White 46(94%) Black 28(57.1%) Hispanic 0 (0%); E‐T group White 46(90%), Black 24(47%), Hispanic3(6%)
‐Run‐in period: a 2‐week, open‐label oestrogen (1.25 mg/day) lead‐in phase
‐Inclusion criteria:
1. 25‐65 year‐old
2. Healthy surgically menopausal women (for a minimum of 3 months)
3. Receiving the equivalent of 0.625 to 1.25 mg of estrogens in oral, topical, or
transdermal form for at least 3 months
4. Stable, monogamous relationship for at least 2 years
5. Hypoactive sexual interest/desire associated with the onset of surgical menopause
‐Exclusion criteria:
1. Sensitivity/contraindications to estrogens or androgens
2. History or concurrent diagnosis of psychiatric disorder, sexual aversion/phobic disorder related or unrelated to sexual trauma/abuse
3. BMI of at least 35 kg/m²
4. Physical limitations interfered with normal sexual functioning
5. Clinical depression or a current depressive disorder
6. Abnormal mammogram or vaginal cytology
7. Undiagnosed abnormal vaginal bleeding/malignancy
8. Grade II or III vaginal vault prolapse
9. Relevant clinical laboratory test abnormalities
10. Receiving other hormones, selective oestrogen receptor modulators, lipid‐lowering
agents, liver enzyme‐inducing drugs, anticoagulants, antidepressants (including selective serotonin reuptake inhibitors, anxiolytics, and herbal and holistic antidepressants), antihypertensive drugs, or herbal remedies claiming libido enhancement.
11. Clinically significant endocrine disease or inadequately controlled DM
12. Stable thyroid medications and antiepileptics for > 3 months.

Interventions

‐Esterified oestrogens (1.25 mg) plus methyltestosterone (2.5 mg) once a day
‐Esterified oestrogens (1.25 mg) alone once a day
‐Route: oral oestrogen and methyltestosterone
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. Sexual function
2. Sense of well being
3. Hirsutism
4. Acne
5. Lipid profile

Notes

‐Baseline equality: no significant differences across treatment groups with regard to age, ethnicity, years since oophorectomy, lipid levels and score of sexual questionnaire.
‐The author was contacted. No further information was supplied.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded

Incomplete outcome data addressed?
All outcomes

Low risk

Missing data have been imputed using appropriate methods

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

High risk

Baseline imbalance (age)

Methods

‐Design: double‐blind randomised (C), parallel group
‐No of centres: three
‐Duration: 2 years
‐Power calculation: not stated
‐Intention‐to‐treat analysis: yes for safety analysis, no for efficacy analysis
‐No of participants randomised: 66 (33 in each group)
‐No of participants analysed: 66 for safety analysis, 48 for BMD(24 in each group), 45 for lipid profile(23 for E group, 22 for E‐T Group)
‐No of non compilers: unclear
‐No of losses to follow up: not stated
‐Compliance assessment: patients were considered compliant if they had taken at least 75% of their medication as assessed by returned tablet counts and monthly phone call
‐Source of funding: drug company

Participants

‐Location: United States
‐Setting: hospital‐based
‐Ethnicity: White (98.3%), Hispanic (1.7%)
‐Run‐in period: no
‐Characteristics: healthy surgically menopausal women
‐Age (SD): E group 45.0 (8.0), E‐T group 48.0 (8.0) yr
‐Inclusion criteria:
1. The same as stated in disease status
2. No concomitant illness
‐Exclusion criteria: not stated

Interventions

‐EE 1.25 mg once a day
‐EE 1.25 mg plus mT 2.5 mg once a day
‐Route: oral
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. BMD of lumbar spines, radius and hip: DEXA
2. Menopausal symptoms: the scale modified from the original version developed by Kuppermann et al.
3. Lipid profile
4. Haematology
‐Other outcomes:
1. Serum biochemistry and urinalysis tests
2. Vaginal cytology

Notes

‐Baseline equality: the two groups were similar in terms of age, height, weight, race, time since oophorectomy, number of patients with oestrogen use in previous 2 years, menopausal symptoms scores and lipid profiles.
‐The author was contacted and the response was obtained but no additional information was provided.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

C ‐ Not stated

Allocation concealment?

Low risk

A ‐ Adequate

Blinding?
All outcomes

Low risk

Participants and key personnel were blinded.

Incomplete outcome data addressed?
All outcomes

High risk

Plausible effect size among missing outcomes enough to induce clinically relevant bias in observed effect size.

Free of selective reporting?

High risk

One or more outcomes of interest in the review are reported incompletely.

Free of other bias?

Unclear risk

Insufficient information

Methods

See Dobs 2002

Participants

See Dobs 2002

Interventions

See Dobs 2002

Outcomes

See Dobs 2002

Notes

See Dobs 2002

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

See Dobs 2002

Allocation concealment?

Low risk

See Dobs 2002

Blinding?
All outcomes

Low risk

See Dobs 2002

Incomplete outcome data addressed?
All outcomes

Low risk

See Dobs 2002

Free of selective reporting?

High risk

See Dobs 2002

Free of other bias?

High risk

See Dobs 2002

Methods

‐Design: open randomised (A), parallel group
‐No of centres: single centre
‐Duration: 12 weeks
‐Power calculation: not stated
‐Intention‐to‐treat analysis: yes by default
‐No of participants randomised: 63(T group 21, E group 22, E‐T group 20)
‐No of participants completed the study: 63
‐No of participants analysed: 63
‐No of non compilers: 0
‐No of losses to follow up: 0
‐Compliance assessment: not stated
‐Source of funding: drug company

Participants

‐Characteristics: naturally menopausal women
‐Age: T group 54.8+4.0, E group 55.4+4.7, E‐T group 55.7 +4.5 yr
‐Location: Sweden
‐Setting: population‐based
‐Ethnicity: unclear
‐Run‐in period: washout periods: 8 weeks for oral HT, 4 weeks for transdermal HT or local oestrogen applications, and 6 months for progestin implants or injections.
‐Inclusion criteria:
1. 44‐64 year‐old
2. BMI 20‐32 kg/m²
3. last menstrual bleeding > 12 months or FSH levels > 30 IU/L
4. Nonsmoker
‐Exclusion criteria:
1. Liver, biliary, or renal disease
2. Uncontrolled high blood pressure
3. Endocrine disorder
4. History or presence of thromboembolic disorder and malignancy

Interventions

‐Testosterone undecanoate (40 mg every second day)
‐oestradiol valerate (2 mg daily)
‐The combination of testosterone undecanoate and oestradiol valerate
‐Route:oral oestrogen and testosterone
‐Co‐intervention: no

Outcomes

‐Relevant outcomes:
1. BMD
2. Body composition
‐Other outcomes:
1. Glucose and insulin levels

Notes

‐Baseline equality: no statistically significant differences across treatment groups with regard to age, weight, BMI, waist‐to‐hip ratio, blood pressure, serum hormone levels, and previous use of HT
‐The author was contacted and kindly provided further information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

A ‐ Adequate

Allocation concealment?

High risk

C ‐ Inadequate

Blinding?
All outcomes

High risk

Open randomised trial

Incomplete outcome data addressed?
All outcomes

Low risk

No missing data

Free of selective reporting?

Unclear risk

Insufficient information

Free of other bias?

Low risk

Possible free of other sources of bias