Cyproterone acetate for hirsutism

Zephne M van der Spuy; Paul Andre Le Roux; Mushi J Matjila

doi:10.1002/14651858.CD001125

Acetato de ciproterona para el hirsutismo

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Referencias

Referencias de los estudios incluidos en esta revisión

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estudios excluidos
otras referencias

Couzinet B, le Strat N, Brailly S, Schaison G. Comparative effects of cyproterone acetate or a long acting gonadotrophin releasing hormone agonist in polycystic ovary disease. Journal of Clinical Endocrinology and Metabolism 1986;63(4):1031‐5.

Dixon JE, Hicks BH, Chapman MG. Hirsutography: photographic measurement of linear hair growth in hirsute women during comparison of anti‐androgen treatments. Journal of Obstetrics and Gynaecology 1991;11(1):63‐7.

Erenus M, Yucelten D, Gurbuz O, Durmusoglu F, Pekin S. Comparison of spironolactone‐oral contraceptive versus cyproterone acetate‐estrogen regimens in the treatment of hirsutism. Fertility and Sterility 1996;22(2):216‐9.

Fruzetti F, Bersi C, Parrini D, Ricci C, Genazzani R. Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects. Fertility and Sterility 1999;71(3):445‐51.

Gokmen O, Senoz B, Gulekli B, Isik AZ. Comparison of four different treatment regimens in hirsutism related to polycystic ovary syndrome. Gynaecological Endocrinology 1996;10(4):249‐55.

Grigoriou O, Papadias C, Konidaris S, Antoniou G, Karakitsos P, Giannikos L. Comparison of flutamide and cyproterone acetate in the treatment of hirsutism: a randomised controlled trial. Gynaecological Endocrinology 1996;10(2):119‐23.

O'Brien RC, Cooper ME, Murray RML, Seeman E, Thomas AK, Jerums G. Comparison of sequential cyproterone acetate/estrogen versus spironolactone /oral contraceptive in the treatment of hirsutism. Journal of Clinical Endocrinology and Metabolism 1991;72(5):1008‐13.

Pazos F, Escobar‐Morreale HF, Balsa J, Sancho JM, Varela C. Prospective randomised study comparing the long‐acting gonadotrophin‐releasing hormone agonist triptorelin, flutamide and cyproterone acetate, used in combination with an oral contraceptive, in the treatment of hirsutism. Fertility and Sterility 1999;71(1):122‐8.

Saeed R, Akram J, Changezi HU, Saeed M. Treatment of hirustism in polycystic ovary syndrome with Diane, 50 mcg ethinyl estradiol and 2mg cyproterone acetate. Pakistan Journal of Medical Science 1993;9(2):109‐12.

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Referencias de los estudios excluidos de esta revisión

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estudios incluidos
otras referencias

Adamopoulos DA, Kampyli S, Georgiacodis F, Kapolla N, Abrahamian‐Michalakis A. Effects of anti‐androgen estrogen treatment on sexual and endocrine parameters in hirsute women. Archives of Sexual Behaviour 1988;17(5):421‐9.

Barth JH, Cherry F, Wojnarowska F, Dawber RPR. Cyproterone acetate for severe hirsutism: results of a double blind dose‐ranging study. Clinical Endocrinology 1991;35(1):5‐10.

Belisle S, Love EJ. Clinical efficacy and safety of cyproterone acetate in severe hirsutism : results of a multicentered Canadian study. Fertility and Sterility 1986;46(6):1015‐20.

Beylot C, Doutre MS, Barry M. Oral contraceptives and cyproterone acetate in female acne treatment. Dermatology 1998;196(1):148‐52.

Carmina E, Lobo RA. The addition of dexamethazone to antiandrogen therapy for hirsutism prolongs the duration of remission. Fertility and Sterility 1998;69(6):1075‐9.

Castelo‐Branco C, Martinez de Osaba MJ, Pons F, Vanrell JA. Effects of bone mass of two oral contraceptives containing ethinylestradiol and cyproterone acetate or desogestrel: results of a two year follow‐up. The European Journal of Contraception and Reproductive Health Care: the Official Journal of the European Society of Contraception 1998;3(2):79‐84.

Consoli SM, Vexiau P, Consoli SG, Abramovici Y. Acceptance, tolerance and effects on quality of life of treatment of hiruste women with cyproterone acetate. Comparison of associated treatment with oral estradiol to transdermal estradiol [Acceptabilite, tolerance et impact sur la qualite de la vie du traitement de la femme hirsute par lacetate de cyproterone. Comparaison de 2 schemas l'associant soit a l' estradiol per os, soit par voie transdermique]. Contraception, Fertilite, Sexualite 1994;22(12):783‐7.

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Frank‐Raue K, Junga G, Raue F, Vecsei P, Ziegler R. Therapy for women with hirsutism with adrenal enzyme defects of enzyme biosynthesis: compared with dexamethazone compbined with cyproterone acetate [Therapie des hirsutismus bei frauen mit adrenalen enzymdefekten der steroidhormonbiosynthese: vergleich von dexamethason mit cyproteronacetat]. Klinische Wochenschrift 1990;68(12):597‐601.

Gruber DM, Sator MO, Joura MO, Kokoscha EM, Heinze G, Huber JC. Topical cyproterone acetate treatment in women with acne: a placebo‐controlled trial. Archives of Dermatology 1998;134(4):459‐63.

Grund E, Schmidt‐Elmendorff H. The treatment of virilizing syndromes. Comparative clinical studies of 2 antiandrogen‐active gestagens (cyproterone acetate, megestrol acetate) [Behandlung von virilisierungs‐ erscheinungen. Vergleichende klinische untersuchung zweier antiandrogenwirksamer gestagene (cyproteronazetat, megestrolazetat)]. Die Medizinische Welt 1975;26(48):2180‐7.

Holdaway IM, Croxson MS, Ibbertson HK, Sheehan A, Knox B, France J. Cyproterone acetate as intial treatment and maintenance therapy for hirsutism. Acta Endocrinologica 1985;109(4):522‐9.

Jasonni VM, Bulletti C, Naldi S, Di Cosmo E, Cappuccini F, Flamigni C. Treatment of hirustism by an association of oral cyproterone acetate and transdermal 17 beta estradiol. Fertility and Sterility 1991;55(4):742‐5.

Kelestimur F, Sahin Y. Comparison of Diane 35 and Diane 35 plus spironolactone in the treatment of hirsutism. Fertility and Sterility 1997;69(1):66‐9.

Kuttenn F, Rigaud C, Wright F, Mauvais‐Jarvis P. Treatment of hirsutism by oral cyproterone acetate and percutaneous estradiol. Journal of Clinical Endocrinology and Metabolism 1980;51(5):1107‐11.

Lachnit‐Fixson U, Kaufmann J. Therapy of androgenisation symptoms [Zur beeinflussung von androgenisierungserscheinungen]. Medizinische Klinik 1977;72(45):1922‐6.

Lachnit‐Fixson U. The development and evaluation of an ovulation inhibitor (Diane) containing an antiandrogen. Acta Obstetricia et Gynecologica Scandinavica 1979;88(Suppl):33‐42.

Marcondes JAM, Wajchenberg BL, Abujamra AC, Luthold WW, Samojlik E, Kirschner MA. Monthly cyproterone acetate in the treatment of hirsute women: clinical and laboratory effects. Fertility and Sterility 1990;53(1):40‐4.

Moltz L, Kaiser E. Medium dose cyproterone acetate therapy for women with moderate hyperandrogenism [Mittelhochdosierte orale cyproteronacetat‐therapie bie frauen mit mittelgradig ausgepragten androgenisierungserscheinungen]. Geburtshilfe und Frauenheilkunde 1984;44(1):47‐52.

Pasquali R, Fabbri R, Venturoli S, Paradisi R, Antenucci D, Melchionda N. Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries. American Journal of Obstetrics and Gynaecology 1986;154(1):139‐44.

Porcile A, Gallardo E. Long term treatment of hirustism: desogestrel compared with cyproterone acetate in oral contraceptives. Fertility and Sterility 1991;55(5):877‐81.

Pucci E, Petraglia F. Treatment of androgen excess in females: yesterday, today and tomorrow. Gynaecological Endocrinology 1997;11(6):411‐33.

Pugeat M, Nicolas MH, Dechaud H, Elmidani M. Administration of cyproterone acetate and natural estrogens in the treatment of hirustism [Association d'acetate de cyproterone et d'estrogenes naturels dans le traitement de l'hirsutisme]. Journal of Obstetrics and Gynaecology and Reproductive Biology 1991;20:1057‐62.

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Rigaud C, Vincens M, Mowszomicz I, Wright F, Mavier P, Nahoul K, et al. Action mechanisms of cyproterone acetate in the treatment of hirustism [Mecamisme d'action de l'acetate de cyproterone dans le traitement de l'hirsutisme]. Annals of Endocrinology 1983;44:387‐92.

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Rittmaster RS. Antiandrogen treatment of polycystic ovary syndrome. Endocrinology and Metabolism Clinics of North America 1999;28(2):409‐21.

Sahin Y, Bayram F, Kelestimur F, Muderris I. Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism. Journal of Endocrinological Investigation 1998;21(6):348‐52.

Schmidt JB, Huber J, Spona J. Parenteral and oral cyproterone acetate treatment in severe hirsutism. Gynecologic and Obstetric Investigation 1987;24(2):125‐30.

Tartagni M, Schonauer LM, de Salvia MA, Cicinelli E, de Pergola G, D'Addario V. Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of hirsutism. Fertility and Sterility 2000;73(4):718‐23.

Thomas AK, Slobodniuk R, Taft J, Cooper M, Montalto J, Jerums G. The treatment of hirustism: experience with cyproterone acetate and spironolactone. Australian Journal of Dermatology 1985;26(19):20‐3.

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van der Spuy ZM, Nugent FA. The managment of hirustism in PCOS using GnRH agonist analogue therapy. Abstract ‐ 27th British Congress of Obstetrics and Gynaecology1995.

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Vegetti W, Testa G, Maggioni P, Motta T, Falsetti L, Crosignani PG. An open randomised comparative study of an oral contraceptive containing ethinyl estradiol and cyproterone acetate with and without the GnRH analogue goserelin in the long term treatment of hirsutism. Gynecologic and Obstetric Investigation 1996;41(4):260‐8.

Venturoli S, Marescalchi O, Colombo FM, Marcelli S, Ravaioli B, Bagnoli A, et al. A prospective randomised trial comparing low dose flutamide, finasteride, ketoconazole and cyproterone acetate‐estrogen regimens in the treatment of hirustism. Journal of Clinical Endocrinology and Metabolism 1999;84(4):1304‐10.

Vermeulen A, Rubens R. Effects of cyproterone acetate plus ethinylestradiol low dose on plasma androgens and lipids in mildly hirsute or acneic young women. Contraception 1988;38(4):419‐28.

Vexiau P, Fiet J, Conard J, Abramovici Y, Boudou P, Hardy N, et al. 17 beta estradiol: oral or parenteral administration in hyperandrogenic women? Metabolic tolerance in association with cyproterone acetate. Fertility and Sterility 1995;63(3):508‐15.

Young R, Sinclair R. Hirsutes II: treatment. Australian Journal of Dermatology 1998;39(3):151‐7.

Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos

Adams J, Polson DW, Franks S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. British Medical Journal Clinical Research Edition 1986;293(6543):355‐9.

Appelt H, Strauss B. Effects of anti‐androgen treatment on the sexuality of women with hyperandrogenism. Psychotherapy and psychosomatics 1984;42(1‐4):177‐81.

Ashton RE, Miller JA, Wojnarowska FT, et al. Antiandrogen treatment in women with acne: a controlled trial. In: Schindler AE editor(s). Antiandrogen‐estrogen therapy for signs of androgenisation. Berlin: Walter de Gruyter, 1987:117‐38.

Bunker CB, Newton JA, Kilborn J, Patel A, Conway GS, Jacobs HS. Most women with acne have polycystic ovaries. British Journal of Dermatology 1989;121(6):675‐80.

Conway GS, Honour JW, Jacobs HS. Heterogeneity of the polycystic ovary syndrome: clinical, endocrine and ultrasound features in 556 patients. Clinical Endocrinology 1989;30(4):459‐70.

Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. Journal of Clinical Endocrinology and Metabolism 1961;21:1440‐7.

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Franks S. Polycystic ovary syndrome: a changing perspective. Clinical Endocrinology 1989;31(1):87‐120.

Hammerstein J, Meckies J, Leo‐Rossberg I, Moltz L, Zielske F. Use of cyproterone acetate (CPA) in the treatment of acne, hirsutism and virilism. Journal of Steroid Biochemistry 1975;6(6):827‐36.

Hammerstein J, Moltz L, Schwartz U. Antiandrogens in the treatment of acne and hirsutism. Journal of Steroid Biochemistry 1983;19(1B):591‐7.

Jones KR, Katz M, Keyzer C, Gordon W. Effect of cyproterone acetate on rate of hair growth in hirsute women. British Journal of Dermatology 1981;105(6):685‐92.

Kuttenn F, Rigaud C, Wright F, Mauvais‐Jarvis P. Treatment of hirsutism by oral cyproterone acetate and percutaneous estradiol. Journal of Clinical Endocrinology and Metabolism 1980;51(5):1107‐11.

Lunnell NO, Zador G, Carlstrom K, Eneroth P, Patek E, Wagner J. The effect of cyproterone acetate on pituitary‐ovarian function and clinical symptoms in hirsute women. Acta Endocrinology 1982;100:91‐7.

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Neumann F. Pharmacological aspects of cyproterone acetate. In: Schindler editor(s). Anti‐androgen estrogen therapy for signs of androgenisation. Berlin: Walter de Gruyter, 1987:23‐40.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Couzinet 1986

Methods	Cross over study. 1 centre. No power calc. 10 women. No withdrawals.
Participants	PCO by clinical and biochemical tests. Age 20‐35. Endo unit, Hospital de Bicentre, France. No exclusion criteria stated.
Interventions	1) CPA 50MG daily. 2) D‐ TRYPTOPHAN 6 LHRH IM monthly injection (GNRH) 3 months study duration for each intervention.
Outcomes	FG score E2,E1,TESTO, DHEAS, ANDROSTENEDIONE, 3ALPHA ANDROSTANEDIOL.
Notes	FG figures not available.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Dixon 1991

Methods	Not blinded. 1 centre. No power calc. 41 women analysed. Withdrawals not stated. No ITT analyses.
Participants	Hirsute women. Age 18‐45. Gynae or Endo clinics, Guys Hospital, London. Exclusion criteria not stated.
Interventions	1) Spironolactone + EE (Ovysmen) 2) CPA + EE 6 months duration.
Outcomes	FG score. Linear hair growth.
Notes	Photographic method for hair measurement.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Erenus 1996

Methods	Single blinding. 1 centre. No power calc. 42 women randomised. 42 analysed. no withdrawals. No intention to treat (ITT) analyses.
Participants	Hirsute women. Age mean group 1 20.1 (SD3.7), group 2 22.3 (SD 5.6). Marmara University School of Medicine. Istanbul, Turkey. Exclusion criteria not stated.
Interventions	1) Spironolactone (100MG) + EE (OC) 2) CPA 50MG Day 1‐10 + EE (OC ‐ Diane) 9 months.
Outcomes	FG score. Testo, DHEAS.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Fruzetti 1999

Methods	Unclear blinding. No power calc. 45 women randomised. 42 analysed. 3 withdrawals for personal reasons. No ITT analyses.
Participants	Women with hirsutism. No hormonal treatment for 6 months prior to study. Age 16‐29 years. Reprod. Endo. OPD Clinic. University of Pisa.
Interventions	1) CA 25MG Day 1‐10 plus EE 20mcg D1‐21. 2) Finasteride 5mg/day 3) Flutamide 250mg daily. No placebo. 12 months.
Outcomes	FG score. Total / free testosterone, androstenedione, DHEAS, SHBG, DHT,3 alpha androstanediol glucuronide.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Gokmen 1996

Methods	Unclear blinding. One centre. 173 women randomised. Two stage randomisation. Second two groups added to randomisation after study already commenced. 141 analysed. 32 withdrawals. No ITT analysis. Source of funding ‐ not stated.
Participants	Complaint hirsutism. PCO on ultrasound + 1 biochemical abnormality. Age 14‐39. Exclusions: ‐ Hyperandrogenism other than ovarian ‐ Failure to come for follow up. Reprod Endo Clinic. Ankara, Turkey.
Interventions	1) Diane 2) CA 100 Day 1‐10 OF Diane + Diane. 3) Spironolactone 100‐200mg individually adjusted. 4) Ketoconazole 400mg daily. Duration 6 months.
Outcomes	FG score. BMI Estradiol Testosterone (free and total) Androstenedione DHEAS
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Grigoriou 1996

Methods	Not blinded. 1 centre. No power calc. 22 women randomised. No withdrawals.
Participants	Idiopathic hirsutism. Age 16‐32. O&G dept, University of Athens, Greece.
Interventions	1) CPA 100mg Day 5‐14. 2) Flutamide 250mg twice daily. 9 months duration.
Outcomes	FG score. Testosterone Androstenedione DHEAS SHBG
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	High risk	C ‐ Inadequate

O'Brien 1990

Methods	Not blinded. 1 centre. No power calc. 50 women randomised. 2 withdrawals for personal reasons. 3 withdrawals during study period. Analysed ‐19 spironolactone and 26 CPA.
Participants	Hirsute women. Cosmetic methods inadequate. Age 19‐46. Excluded: cliteromegaly. Endo Dept. Autin University Hospital. Heidelberg, Victoria, Australia.
Interventions	1) Spironolactone (100mg) + EE 2) CPA (100mg) Day 5‐14 + EE 6 months duration.
Outcomes	Hair diameter. Testosterone Androstenedione DHEAS SHBG
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Pazos 1999

Methods	Unclear blinding. 39 randomised. 33 analysed. 6 withdrawals. No ITT analyses.
Participants	Idiopathic and ovarian hirsutism. Exclusion: adrenal hyperandrogenism. Dept Endo, Hospital Ramon Ycajal, Madrid, Spain.
Interventions	1) Triptorelin 3.75mg IM every 28 days 2) CA 100mg Day 1‐10 3) Flutamide 250mg twice daily. All patients on COCP. 9 months duration.
Outcomes	FG score Endocrine measurements.
Notes	Endocrine values not available ‐ only graphs.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Saeed 1993

Methods	Double blinded study. 1 centre. No power calc. 20 women randomised and analysed.
Participants	PCOS with hirsutism. Age 17‐31. Exclusion criteria not stated. Iqbal Medical College, Lahore.
Interventions	1) CPA (2mg) + EE ‐ Diane 2) Placebo 12 months
Outcomes	Subjective improvement in hirsutism. Testosterone DHEAS
Notes	Endocrine values not available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Adamopoulous 1988	Assessment of sexual activity before and after treatment with CPA. Not randomised study.
Barth 1991	Mean data not presented in paper. Cannot be used in meta‐analysis.
Belisle 1986	Randomised study. Insufficient data given for analysis.
Beylot 1998	Review, not original study.
Carmina 1998	No CPA included in groups.
Castelo‐Branco 1998	Effects of CPA on bone mass. Not hirsute women.
Consoli 1994	Randomised study comparing 2 routes of estrogen administration. Both groups received CPA.
Cremoncini 1976	Not randomised
Erkkola 1990	Some women only acne, not hirsutism.
Frank‐Raue 1990	Not randomised.
Gruber 1998	Topical CPA therapy.
Grund 1975	Not a randomised study.
Holdaway 1985	Women pre‐treated with study drug prior to randomisation.
Jasonni 1991	Not randomised.
Kelestimur 1997	Both groups contain CPA. Study to compare the additive effect of spironolactone with CPA.
Kuttenn 1980	Not randomised.
Lachnit‐Fixson 1977	Women with acne without hirsutism included.
Lachnit‐Fixson 1979	Review, not original study.
Marcondes 1990	Not randomised. No control.
Moltz 1984	Women with acne or hirsutism recruited. Unable to differentiate groups in the results.
Pasquali 1986	Randomised study of two diet regimes. CPA in both groups.
Porcile 1991	Outcome data not available.
Pucci 1997	Review. Not original study.
Pugeat 1991	Not randomised.
Rigaud 1983	Not randomised.
Rittmaster 1999	Review. Not original study.
Sahin 1998	Not randomised.
Schmidt 1987	Both groups contain CPA. Dose finding study.
Tartagni 2000	Both groups contain Diane. Study assessing the additive effect of adding finasteride.
Thomas 1985	Not randomised.
van der Spuy 1995	Both groups contain CPA. Study to assess the additive effect of GnRH agonist analogue.
Vegetti 1996	Both groups contain CPA. A study to assess the additive effect of GnRH agonist analogue.
Ventoroli 1999	14 women in study had non‐classical congenital adrenal hyperplasia.
Vermeulen 1988	Both groups contain Diane (CPA). A study to assess two doses of estradiol.
Vexiau 1995	Randomised study of two routes of estrogen therapy.
Young 1998	Review. Not original study.

Data and analyses

Open in table viewer

Comparison 2. CPA (2MG) + EE versus PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SUBJECTIVE IMPROVEMENT IN HAIR GROWTH Show forest plot	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	45.0 [2.01, 1006.75]
Open in figure viewer Analysis 2.1 Comparison 2 CPA (2MG) + EE versus PLACEBO, Outcome 1 SUBJECTIVE IMPROVEMENT IN HAIR GROWTH.

Open in table viewer

Comparison 3. CPA (>2MG) + EE versus CPA(2MG) + EE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	1.10 [‐0.71, 2.91]
Open in figure viewer Analysis 3.1 Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 1 FERRIMAN GALLWEY AT 6 MONTHS.
2 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	‐0.49 [‐1.78, 0.80]
Open in figure viewer Analysis 3.2 Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 2 TESTOSTERONE (TOTAL) AT 6 MONTHS.
3 TESTOSTERONE LEVEL (FREE) AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.61, 1.31]
Open in figure viewer Analysis 3.3 Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 3 TESTOSTERONE LEVEL (FREE) AT 6 MONTHS.
4 ANDROSTENEDIONE LEVEL AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	‐0.35 [‐1.32, 0.62]
Open in figure viewer Analysis 3.4 Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 4 ANDROSTENEDIONE LEVEL AT 6 MONTHS.
5 DHEAS LEVEL AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	0.18 [1.00, 1.36]
Open in figure viewer Analysis 3.5 Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 5 DHEAS LEVEL AT 6 MONTHS.
6 ESTRADIOL LEVEL AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	‐19.0 [‐103.67, 65.67]
Open in figure viewer Analysis 3.6 Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 6 ESTRADIOL LEVEL AT 6 MONTHS.

Open in table viewer

Comparison 4. CPA versus KETOCONAZOLE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	0.70 [‐0.84, 2.24]
Open in figure viewer Analysis 4.1 Comparison 4 CPA versus KETOCONAZOLE, Outcome 1 FERRIMAN GALLWEY AT 6 MONTHS.
2 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.37, 0.33]
Open in figure viewer Analysis 4.2 Comparison 4 CPA versus KETOCONAZOLE, Outcome 2 TESTOSTERONE (TOTAL) AT 6 MONTHS.
3 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	1.39 [0.43, 2.35]
Open in figure viewer Analysis 4.3 Comparison 4 CPA versus KETOCONAZOLE, Outcome 3 TESTOSTERONE (FREE) AT 6 MONTHS.
4 ANDROSTENEDIONE AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.62, 1.32]
Open in figure viewer Analysis 4.4 Comparison 4 CPA versus KETOCONAZOLE, Outcome 4 ANDROSTENEDIONE AT 6 MONTHS.
5 DHEAS AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	2.87 [1.99, 3.75]
Open in figure viewer Analysis 4.5 Comparison 4 CPA versus KETOCONAZOLE, Outcome 5 DHEAS AT 6 MONTHS.
6 ESTRADIOL AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	135.0 [59.92, 210.08]
Open in figure viewer Analysis 4.6 Comparison 4 CPA versus KETOCONAZOLE, Outcome 6 ESTRADIOL AT 6 MONTHS.

Open in table viewer

Comparison 5. CPA versus SPIRONOLACTONE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 WITHDRAWALS DURING TREATMENT Show forest plot	1	48	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.03, 4.33]
Open in figure viewer Analysis 5.1 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 1 WITHDRAWALS DURING TREATMENT.
2 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	2	83	Mean Difference (IV, Fixed, 95% CI)	‐1.98 [‐4.12, 0.16]
Open in figure viewer Analysis 5.2 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 2 FERRIMAN GALLWEY AT 3 MONTHS.
3 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	3	160	Mean Difference (IV, Fixed, 95% CI)	‐1.35 [‐2.87, 0.18]
Open in figure viewer Analysis 5.3 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 3 FERRIMAN GALLWEY AT 6 MONTHS.
4 SIDE EFFECTS DURING TREATMENT Show forest plot	2	90	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.21, 2.70]
Open in figure viewer Analysis 5.4 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 4 SIDE EFFECTS DURING TREATMENT.
5 LINEAR HAIR GROWTH AT 3 MONTHS Show forest plot	1	41	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.03, 0.07]
Open in figure viewer Analysis 5.5 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 5 LINEAR HAIR GROWTH AT 3 MONTHS.
6 LINEAR HAIR GROWTH AT 6 MONTHS Show forest plot	1	41	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.09, 0.01]
Open in figure viewer Analysis 5.6 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 6 LINEAR HAIR GROWTH AT 6 MONTHS.
7 HAIR SHAFT DIAMETER AT 6 MONTHS Show forest plot	1	45	Mean Difference (IV, Fixed, 95% CI)	3.00 [‐23.85, 29.85]
Open in figure viewer Analysis 5.7 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 7 HAIR SHAFT DIAMETER AT 6 MONTHS.
8 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	3	164	Mean Difference (IV, Fixed, 95% CI)	‐0.00 [‐0.28, 0.27]
Open in figure viewer Analysis 5.8 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 8 TESTOSTERONE (TOTAL) AT 6 MONTHS.
9 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	77	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.62, 1.32]
Open in figure viewer Analysis 5.9 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 9 TESTOSTERONE (FREE) AT 6 MONTHS.
10 ANDROSTENEDIONE AT 6 MONTHS Show forest plot	2	122	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐1.66, 1.25]
Open in figure viewer Analysis 5.10 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 10 ANDROSTENEDIONE AT 6 MONTHS.
11 DHEAS AT 6 MONTHS Show forest plot	3	164	Mean Difference (IV, Fixed, 95% CI)	‐0.74 [‐1.71, 0.24]
Open in figure viewer Analysis 5.11 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 11 DHEAS AT 6 MONTHS.
12 SHBG AT 6 MONTHS Show forest plot	1	45	Mean Difference (IV, Fixed, 95% CI)	9.20 [‐27.20, 45.60]
Open in figure viewer Analysis 5.12 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 12 SHBG AT 6 MONTHS.
13 ESTRADIOL AT 6 MONTHS Show forest plot	1	77	Mean Difference (IV, Fixed, 95% CI)	119.00 [10.84, 227.16]
Open in figure viewer Analysis 5.13 Comparison 5 CPA versus SPIRONOLACTONE, Outcome 13 ESTRADIOL AT 6 MONTHS.

Open in table viewer

Comparison 6. CPA versus FLUTAMIDE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 WITHDRAWALS FROM TREATMENT Show forest plot	1	26	Odds Ratio (M‐H, Fixed, 95% CI)	3.6 [0.32, 40.23]
Open in figure viewer Analysis 6.1 Comparison 6 CPA versus FLUTAMIDE, Outcome 1 WITHDRAWALS FROM TREATMENT.
2 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	3	72	Mean Difference (IV, Fixed, 95% CI)	0.37 [‐1.22, 1.95]
Open in figure viewer Analysis 6.2 Comparison 6 CPA versus FLUTAMIDE, Outcome 2 FERRIMAN GALLWEY AT 3 MONTHS.
3 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	2	50	Mean Difference (IV, Fixed, 95% CI)	1.50 [‐1.06, 4.06]
Open in figure viewer Analysis 6.3 Comparison 6 CPA versus FLUTAMIDE, Outcome 3 FERRIMAN GALLWEY AT 6 MONTHS.
4 FERRIMAN GALLWEY AT 12 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	4.5 [0.47, 8.53]
Open in figure viewer Analysis 6.4 Comparison 6 CPA versus FLUTAMIDE, Outcome 4 FERRIMAN GALLWEY AT 12 MONTHS.
5 SIDE EFFECTS Show forest plot	3	73	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.17, 2.51]
Open in figure viewer Analysis 6.5 Comparison 6 CPA versus FLUTAMIDE, Outcome 5 SIDE EFFECTS.
6 TESTOSTERONE (TOTAL) AT 3 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.45, 0.45]
Open in figure viewer Analysis 6.6 Comparison 6 CPA versus FLUTAMIDE, Outcome 6 TESTOSTERONE (TOTAL) AT 3 MONTHS.
7 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	‐0.69 [‐1.14, ‐0.24]
Open in figure viewer Analysis 6.7 Comparison 6 CPA versus FLUTAMIDE, Outcome 7 TESTOSTERONE (TOTAL) AT 6 MONTHS.
8 TESTOSTERONE (FREE) AT 3 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	‐5.37 [‐10.29, ‐0.45]
Open in figure viewer Analysis 6.8 Comparison 6 CPA versus FLUTAMIDE, Outcome 8 TESTOSTERONE (FREE) AT 3 MONTHS.
9 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	‐4.16 [‐6.62, ‐1.70]
Open in figure viewer Analysis 6.9 Comparison 6 CPA versus FLUTAMIDE, Outcome 9 TESTOSTERONE (FREE) AT 6 MONTHS.
10 TESTOSTERONE (FREE) AT 12 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	‐4.55 [‐7.43, ‐1.67]
Open in figure viewer Analysis 6.10 Comparison 6 CPA versus FLUTAMIDE, Outcome 10 TESTOSTERONE (FREE) AT 12 MONTHS.
11 ANDROSTENEDIONE AT 3 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	‐2.79 [‐6.51, 0.93]
Open in figure viewer Analysis 6.11 Comparison 6 CPA versus FLUTAMIDE, Outcome 11 ANDROSTENEDIONE AT 3 MONTHS.
12 ANDROSTENEDIONE AT 6 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	‐2.45 [‐5.90, 1.00]
Open in figure viewer Analysis 6.12 Comparison 6 CPA versus FLUTAMIDE, Outcome 12 ANDROSTENEDIONE AT 6 MONTHS.
13 DHEAS AT 3 MONTHS Show forest plot	2	50	Mean Difference (IV, Fixed, 95% CI)	0.41 [‐0.04, 0.85]
Open in figure viewer Analysis 6.13 Comparison 6 CPA versus FLUTAMIDE, Outcome 13 DHEAS AT 3 MONTHS.
14 DHEAS AT 6 MONTHS Show forest plot	2	50	Mean Difference (IV, Fixed, 95% CI)	0.28 [‐0.31, 0.87]
Open in figure viewer Analysis 6.14 Comparison 6 CPA versus FLUTAMIDE, Outcome 14 DHEAS AT 6 MONTHS.
15 DHEAS AT 12 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	1.16 [‐0.38, 2.70]
Open in figure viewer Analysis 6.15 Comparison 6 CPA versus FLUTAMIDE, Outcome 15 DHEAS AT 12 MONTHS.
16 SHBG AT 3 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	1.19 [‐1.57, 3.95]
Open in figure viewer Analysis 6.16 Comparison 6 CPA versus FLUTAMIDE, Outcome 16 SHBG AT 3 MONTHS.
17 SHBG AT 6 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	1.17 [‐2.42, 4.76]
Open in figure viewer Analysis 6.17 Comparison 6 CPA versus FLUTAMIDE, Outcome 17 SHBG AT 6 MONTHS.

Open in table viewer

Comparison 7. CPA versus FINASTERIDE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	4.70 [‐1.86, 11.26]
Open in figure viewer Analysis 7.1 Comparison 7 CPA versus FINASTERIDE, Outcome 1 FERRIMAN GALLWEY AT 3 MONTHS.
2 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐5.50, 5.10]
Open in figure viewer Analysis 7.2 Comparison 7 CPA versus FINASTERIDE, Outcome 2 FERRIMAN GALLWEY AT 6 MONTHS.
3 FERRIMAN GALLWEY AT 12 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐5.09, 4.89]
Open in figure viewer Analysis 7.3 Comparison 7 CPA versus FINASTERIDE, Outcome 3 FERRIMAN GALLWEY AT 12 MONTHS.
4 TESTOSTERONE (TOTAL) AT 3 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐1.11 [‐1.81, ‐0.41]
Open in figure viewer Analysis 7.4 Comparison 7 CPA versus FINASTERIDE, Outcome 4 TESTOSTERONE (TOTAL) AT 3 MONTHS.
5 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐1.60 [‐2.39, ‐0.81]
Open in figure viewer Analysis 7.5 Comparison 7 CPA versus FINASTERIDE, Outcome 5 TESTOSTERONE (TOTAL) AT 6 MONTHS.
6 TESTOSTERONE (TOTAL) AT 12 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐2.08 [‐3.13, ‐1.03]
Open in figure viewer Analysis 7.6 Comparison 7 CPA versus FINASTERIDE, Outcome 6 TESTOSTERONE (TOTAL) AT 12 MONTHS.
7 TESTOSTERONE (FREE) AT 3 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐4.72 [‐7.69, ‐1.75]
Open in figure viewer Analysis 7.7 Comparison 7 CPA versus FINASTERIDE, Outcome 7 TESTOSTERONE (FREE) AT 3 MONTHS.
8 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐9.02 [‐12.44, ‐5.60]
Open in figure viewer Analysis 7.8 Comparison 7 CPA versus FINASTERIDE, Outcome 8 TESTOSTERONE (FREE) AT 6 MONTHS.
9 TESTOSTERONE (FREE) AT 12 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐11.70 [‐15.67, ‐7.73]
Open in figure viewer Analysis 7.9 Comparison 7 CPA versus FINASTERIDE, Outcome 9 TESTOSTERONE (FREE) AT 12 MONTHS.
10 3 ALPHA ANDROSTENEDIOL GLUCORONIDE AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.71 [‐5.05, 3.63]
Open in figure viewer Analysis 7.10 Comparison 7 CPA versus FINASTERIDE, Outcome 10 3 ALPHA ANDROSTENEDIOL GLUCORONIDE AT 6 MONTHS.

Open in table viewer

Comparison 8. CPA versus GNRH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SIDE EFFECTS Show forest plot	1	21	Odds Ratio (M‐H, Fixed, 95% CI)	1.93 [0.25, 14.89]
Open in figure viewer Analysis 8.1 Comparison 8 CPA versus GNRH, Outcome 1 SIDE EFFECTS.
2 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	1	21	Mean Difference (IV, Fixed, 95% CI)	‐2.80 [‐5.85, 0.25]
Open in figure viewer Analysis 8.2 Comparison 8 CPA versus GNRH, Outcome 2 FERRIMAN GALLWEY AT 3 MONTHS.
3 TESTOSTERONE (TOTAL) AT 3 MONTHS Show forest plot	1	20	Mean Difference (IV, Fixed, 95% CI)	0.17 [‐0.15, 0.49]
Open in figure viewer Analysis 8.3 Comparison 8 CPA versus GNRH, Outcome 3 TESTOSTERONE (TOTAL) AT 3 MONTHS.
4 ANDROSTENEDIONE AT 3 MONTHS Show forest plot	1	20	Mean Difference (IV, Fixed, 95% CI)	0.66 [‐0.44, 1.76]
Open in figure viewer Analysis 8.4 Comparison 8 CPA versus GNRH, Outcome 4 ANDROSTENEDIONE AT 3 MONTHS.

Analysis 2.1

Comparison 2 CPA (2MG) + EE versus PLACEBO, Outcome 1 SUBJECTIVE IMPROVEMENT IN HAIR GROWTH.

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Analysis 3.1

Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 1 FERRIMAN GALLWEY AT 6 MONTHS.

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Analysis 3.2

Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 2 TESTOSTERONE (TOTAL) AT 6 MONTHS.

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Analysis 3.3

Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 3 TESTOSTERONE LEVEL (FREE) AT 6 MONTHS.

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Analysis 3.4

Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 4 ANDROSTENEDIONE LEVEL AT 6 MONTHS.

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Analysis 3.5

Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 5 DHEAS LEVEL AT 6 MONTHS.

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Analysis 3.6

Comparison 3 CPA (>2MG) + EE versus CPA(2MG) + EE, Outcome 6 ESTRADIOL LEVEL AT 6 MONTHS.

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Analysis 4.1

Comparison 4 CPA versus KETOCONAZOLE, Outcome 1 FERRIMAN GALLWEY AT 6 MONTHS.

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Analysis 4.2

Comparison 4 CPA versus KETOCONAZOLE, Outcome 2 TESTOSTERONE (TOTAL) AT 6 MONTHS.

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Analysis 4.3

Comparison 4 CPA versus KETOCONAZOLE, Outcome 3 TESTOSTERONE (FREE) AT 6 MONTHS.

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Analysis 4.4

Comparison 4 CPA versus KETOCONAZOLE, Outcome 4 ANDROSTENEDIONE AT 6 MONTHS.

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Analysis 4.5

Comparison 4 CPA versus KETOCONAZOLE, Outcome 5 DHEAS AT 6 MONTHS.

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Analysis 4.6

Comparison 4 CPA versus KETOCONAZOLE, Outcome 6 ESTRADIOL AT 6 MONTHS.

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Analysis 5.1

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 1 WITHDRAWALS DURING TREATMENT.

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Analysis 5.2

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 2 FERRIMAN GALLWEY AT 3 MONTHS.

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Analysis 5.3

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 3 FERRIMAN GALLWEY AT 6 MONTHS.

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Analysis 5.4

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 4 SIDE EFFECTS DURING TREATMENT.

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Analysis 5.5

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 5 LINEAR HAIR GROWTH AT 3 MONTHS.

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Analysis 5.6

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 6 LINEAR HAIR GROWTH AT 6 MONTHS.

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Analysis 5.7

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 7 HAIR SHAFT DIAMETER AT 6 MONTHS.

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Analysis 5.8

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 8 TESTOSTERONE (TOTAL) AT 6 MONTHS.

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Analysis 5.9

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 9 TESTOSTERONE (FREE) AT 6 MONTHS.

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Analysis 5.10

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 10 ANDROSTENEDIONE AT 6 MONTHS.

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Analysis 5.11

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 11 DHEAS AT 6 MONTHS.

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Analysis 5.12

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 12 SHBG AT 6 MONTHS.

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Analysis 5.13

Comparison 5 CPA versus SPIRONOLACTONE, Outcome 13 ESTRADIOL AT 6 MONTHS.

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Analysis 6.1

Comparison 6 CPA versus FLUTAMIDE, Outcome 1 WITHDRAWALS FROM TREATMENT.

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Analysis 6.2

Comparison 6 CPA versus FLUTAMIDE, Outcome 2 FERRIMAN GALLWEY AT 3 MONTHS.

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Analysis 6.3

Comparison 6 CPA versus FLUTAMIDE, Outcome 3 FERRIMAN GALLWEY AT 6 MONTHS.

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Analysis 6.4

Comparison 6 CPA versus FLUTAMIDE, Outcome 4 FERRIMAN GALLWEY AT 12 MONTHS.

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Analysis 6.5

Comparison 6 CPA versus FLUTAMIDE, Outcome 5 SIDE EFFECTS.

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Analysis 6.6

Comparison 6 CPA versus FLUTAMIDE, Outcome 6 TESTOSTERONE (TOTAL) AT 3 MONTHS.

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Analysis 6.7

Comparison 6 CPA versus FLUTAMIDE, Outcome 7 TESTOSTERONE (TOTAL) AT 6 MONTHS.

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Analysis 6.8

Comparison 6 CPA versus FLUTAMIDE, Outcome 8 TESTOSTERONE (FREE) AT 3 MONTHS.

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Analysis 6.9

Comparison 6 CPA versus FLUTAMIDE, Outcome 9 TESTOSTERONE (FREE) AT 6 MONTHS.

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Analysis 6.10

Comparison 6 CPA versus FLUTAMIDE, Outcome 10 TESTOSTERONE (FREE) AT 12 MONTHS.

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Analysis 6.11

Comparison 6 CPA versus FLUTAMIDE, Outcome 11 ANDROSTENEDIONE AT 3 MONTHS.

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Analysis 6.12

Comparison 6 CPA versus FLUTAMIDE, Outcome 12 ANDROSTENEDIONE AT 6 MONTHS.

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Analysis 6.13

Comparison 6 CPA versus FLUTAMIDE, Outcome 13 DHEAS AT 3 MONTHS.

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Analysis 6.14

Comparison 6 CPA versus FLUTAMIDE, Outcome 14 DHEAS AT 6 MONTHS.

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Analysis 6.15

Comparison 6 CPA versus FLUTAMIDE, Outcome 15 DHEAS AT 12 MONTHS.

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Analysis 6.16

Comparison 6 CPA versus FLUTAMIDE, Outcome 16 SHBG AT 3 MONTHS.

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Analysis 6.17

Comparison 6 CPA versus FLUTAMIDE, Outcome 17 SHBG AT 6 MONTHS.

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Analysis 7.1

Comparison 7 CPA versus FINASTERIDE, Outcome 1 FERRIMAN GALLWEY AT 3 MONTHS.

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Analysis 7.2

Comparison 7 CPA versus FINASTERIDE, Outcome 2 FERRIMAN GALLWEY AT 6 MONTHS.

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Analysis 7.3

Comparison 7 CPA versus FINASTERIDE, Outcome 3 FERRIMAN GALLWEY AT 12 MONTHS.

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Analysis 7.4

Comparison 7 CPA versus FINASTERIDE, Outcome 4 TESTOSTERONE (TOTAL) AT 3 MONTHS.

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Analysis 7.5

Comparison 7 CPA versus FINASTERIDE, Outcome 5 TESTOSTERONE (TOTAL) AT 6 MONTHS.

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Analysis 7.6

Comparison 7 CPA versus FINASTERIDE, Outcome 6 TESTOSTERONE (TOTAL) AT 12 MONTHS.

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Analysis 7.7

Comparison 7 CPA versus FINASTERIDE, Outcome 7 TESTOSTERONE (FREE) AT 3 MONTHS.

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Analysis 7.8

Comparison 7 CPA versus FINASTERIDE, Outcome 8 TESTOSTERONE (FREE) AT 6 MONTHS.

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Analysis 7.9

Comparison 7 CPA versus FINASTERIDE, Outcome 9 TESTOSTERONE (FREE) AT 12 MONTHS.

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Analysis 7.10

Comparison 7 CPA versus FINASTERIDE, Outcome 10 3 ALPHA ANDROSTENEDIOL GLUCORONIDE AT 6 MONTHS.

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Analysis 8.1

Comparison 8 CPA versus GNRH, Outcome 1 SIDE EFFECTS.

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Analysis 8.2

Comparison 8 CPA versus GNRH, Outcome 2 FERRIMAN GALLWEY AT 3 MONTHS.

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Analysis 8.3

Comparison 8 CPA versus GNRH, Outcome 3 TESTOSTERONE (TOTAL) AT 3 MONTHS.

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Analysis 8.4

Comparison 8 CPA versus GNRH, Outcome 4 ANDROSTENEDIONE AT 3 MONTHS.

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Comparison 2. CPA (2MG) + EE versus PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SUBJECTIVE IMPROVEMENT IN HAIR GROWTH Show forest plot	1	20	Odds Ratio (M‐H, Fixed, 95% CI)	45.0 [2.01, 1006.75]

Comparison 2. CPA (2MG) + EE versus PLACEBO

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Comparison 3. CPA (>2MG) + EE versus CPA(2MG) + EE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	1.10 [‐0.71, 2.91]

2 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	‐0.49 [‐1.78, 0.80]

3 TESTOSTERONE LEVEL (FREE) AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.61, 1.31]

4 ANDROSTENEDIONE LEVEL AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	‐0.35 [‐1.32, 0.62]

5 DHEAS LEVEL AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	0.18 [1.00, 1.36]

6 ESTRADIOL LEVEL AT 6 MONTHS Show forest plot	1	113	Mean Difference (IV, Fixed, 95% CI)	‐19.0 [‐103.67, 65.67]

Comparison 3. CPA (>2MG) + EE versus CPA(2MG) + EE

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Comparison 4. CPA versus KETOCONAZOLE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	0.70 [‐0.84, 2.24]

2 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.37, 0.33]

3 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	1.39 [0.43, 2.35]

4 ANDROSTENEDIONE AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.62, 1.32]

5 DHEAS AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	2.87 [1.99, 3.75]

6 ESTRADIOL AT 6 MONTHS Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	135.0 [59.92, 210.08]

Comparison 4. CPA versus KETOCONAZOLE

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Comparison 5. CPA versus SPIRONOLACTONE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 WITHDRAWALS DURING TREATMENT Show forest plot	1	48	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.03, 4.33]

2 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	2	83	Mean Difference (IV, Fixed, 95% CI)	‐1.98 [‐4.12, 0.16]

3 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	3	160	Mean Difference (IV, Fixed, 95% CI)	‐1.35 [‐2.87, 0.18]

4 SIDE EFFECTS DURING TREATMENT Show forest plot	2	90	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.21, 2.70]

5 LINEAR HAIR GROWTH AT 3 MONTHS Show forest plot	1	41	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.03, 0.07]

6 LINEAR HAIR GROWTH AT 6 MONTHS Show forest plot	1	41	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.09, 0.01]

7 HAIR SHAFT DIAMETER AT 6 MONTHS Show forest plot	1	45	Mean Difference (IV, Fixed, 95% CI)	3.00 [‐23.85, 29.85]

8 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	3	164	Mean Difference (IV, Fixed, 95% CI)	‐0.00 [‐0.28, 0.27]

9 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	77	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.62, 1.32]

10 ANDROSTENEDIONE AT 6 MONTHS Show forest plot	2	122	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐1.66, 1.25]

11 DHEAS AT 6 MONTHS Show forest plot	3	164	Mean Difference (IV, Fixed, 95% CI)	‐0.74 [‐1.71, 0.24]

12 SHBG AT 6 MONTHS Show forest plot	1	45	Mean Difference (IV, Fixed, 95% CI)	9.20 [‐27.20, 45.60]

13 ESTRADIOL AT 6 MONTHS Show forest plot	1	77	Mean Difference (IV, Fixed, 95% CI)	119.00 [10.84, 227.16]

Comparison 5. CPA versus SPIRONOLACTONE

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Comparison 6. CPA versus FLUTAMIDE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 WITHDRAWALS FROM TREATMENT Show forest plot	1	26	Odds Ratio (M‐H, Fixed, 95% CI)	3.6 [0.32, 40.23]

2 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	3	72	Mean Difference (IV, Fixed, 95% CI)	0.37 [‐1.22, 1.95]

3 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	2	50	Mean Difference (IV, Fixed, 95% CI)	1.50 [‐1.06, 4.06]

4 FERRIMAN GALLWEY AT 12 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	4.5 [0.47, 8.53]

5 SIDE EFFECTS Show forest plot	3	73	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.17, 2.51]

6 TESTOSTERONE (TOTAL) AT 3 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.45, 0.45]

7 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	‐0.69 [‐1.14, ‐0.24]

8 TESTOSTERONE (FREE) AT 3 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	‐5.37 [‐10.29, ‐0.45]

9 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	‐4.16 [‐6.62, ‐1.70]

10 TESTOSTERONE (FREE) AT 12 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	‐4.55 [‐7.43, ‐1.67]

11 ANDROSTENEDIONE AT 3 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	‐2.79 [‐6.51, 0.93]

12 ANDROSTENEDIONE AT 6 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	‐2.45 [‐5.90, 1.00]

13 DHEAS AT 3 MONTHS Show forest plot	2	50	Mean Difference (IV, Fixed, 95% CI)	0.41 [‐0.04, 0.85]

14 DHEAS AT 6 MONTHS Show forest plot	2	50	Mean Difference (IV, Fixed, 95% CI)	0.28 [‐0.31, 0.87]

15 DHEAS AT 12 MONTHS Show forest plot	1	28	Mean Difference (IV, Fixed, 95% CI)	1.16 [‐0.38, 2.70]

16 SHBG AT 3 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	1.19 [‐1.57, 3.95]

17 SHBG AT 6 MONTHS Show forest plot	1	22	Mean Difference (IV, Fixed, 95% CI)	1.17 [‐2.42, 4.76]

Comparison 6. CPA versus FLUTAMIDE

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Comparison 7. CPA versus FINASTERIDE

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	4.70 [‐1.86, 11.26]

2 FERRIMAN GALLWEY AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐5.50, 5.10]

3 FERRIMAN GALLWEY AT 12 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐5.09, 4.89]

4 TESTOSTERONE (TOTAL) AT 3 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐1.11 [‐1.81, ‐0.41]

5 TESTOSTERONE (TOTAL) AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐1.60 [‐2.39, ‐0.81]

6 TESTOSTERONE (TOTAL) AT 12 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐2.08 [‐3.13, ‐1.03]

7 TESTOSTERONE (FREE) AT 3 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐4.72 [‐7.69, ‐1.75]

8 TESTOSTERONE (FREE) AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐9.02 [‐12.44, ‐5.60]

9 TESTOSTERONE (FREE) AT 12 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐11.70 [‐15.67, ‐7.73]

10 3 ALPHA ANDROSTENEDIOL GLUCORONIDE AT 6 MONTHS Show forest plot	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.71 [‐5.05, 3.63]

Comparison 7. CPA versus FINASTERIDE

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Comparison 8. CPA versus GNRH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SIDE EFFECTS Show forest plot	1	21	Odds Ratio (M‐H, Fixed, 95% CI)	1.93 [0.25, 14.89]

2 FERRIMAN GALLWEY AT 3 MONTHS Show forest plot	1	21	Mean Difference (IV, Fixed, 95% CI)	‐2.80 [‐5.85, 0.25]

3 TESTOSTERONE (TOTAL) AT 3 MONTHS Show forest plot	1	20	Mean Difference (IV, Fixed, 95% CI)	0.17 [‐0.15, 0.49]

4 ANDROSTENEDIONE AT 3 MONTHS Show forest plot	1	20	Mean Difference (IV, Fixed, 95% CI)	0.66 [‐0.44, 1.76]

Comparison 8. CPA versus GNRH

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Referencias

Referencias de los estudios incluidos en esta revisión

Couzinet 1986 {published data only}

Dixon 1991 {published data only}

Erenus 1996 {published data only}

Fruzetti 1999 {published data only}

Gokmen 1996 {published data only}

Grigoriou 1996 {published data only}

O'Brien 1990 {published data only}

Pazos 1999 {published data only}

Saeed 1993 {published data only}

Referencias de los estudios excluidos de esta revisión

Adamopoulous 1988 {published data only}

Barth 1991 {published data only}

Belisle 1986 {published data only}

Beylot 1998 {published data only}

Carmina 1998 {published data only}

Castelo‐Branco 1998 {published data only}

Consoli 1994 {published data only}

Cremoncini 1976 {published data only}

Erkkola 1990 {published data only}

Frank‐Raue 1990 {published data only}

Gruber 1998 {published data only}

Grund 1975 {published data only}

Holdaway 1985 {published data only}

Jasonni 1991 {published data only}

Kelestimur 1997 {published data only}

Kuttenn 1980 {published data only}

Lachnit‐Fixson 1977 {published data only}

Lachnit‐Fixson 1979 {published data only}

Marcondes 1990 {published data only}

Moltz 1984 {published data only}

Pasquali 1986 {published data only}

Porcile 1991 {published data only}

Pucci 1997 {published data only}

Pugeat 1991 {published data only}

Rigaud 1983 {published data only}

Rittmaster 1999 {published data only}

Sahin 1998 {published data only}

Schmidt 1987 {published data only}

Tartagni 2000 {published data only}

Thomas 1985 {published data only}

van der Spuy 1995 {unpublished data only}

Vegetti 1996 {published data only}

Ventoroli 1999 {published data only}

Vermeulen 1988 {published data only}

Vexiau 1995 {published data only}

Young 1998 {published data only}

Referencias adicionales

Adams 1986

Appelt 1984

Ashton 1987

Bunker 1989

Conway 1989

Ferriman 1961

Flamigni 1971

Franks 1989

Hammerstein 1975

Hammerstein 1983

Jones 1981

Kuttenn 1980

Lunnell 1982

McKnight 1984

Mowszowicz 1981

Mowszowicz 1983

Neumann 1987

Nurnberger 1987

Reed 1988

Rubens1984

Saitoh 1970

Seago 1985

van der spuy 1992

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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