Treatments for suppression of lactation

Olufemi T Oladapo; Bukola Fawole

doi:10.1002/14651858.CD005937.pub3

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Figure 1

'Risk of bias' graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.

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Figure 2

'Risk of bias' summary: review authors' judgments about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Ergot derivatives versus placebo, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days postpartum.

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Analysis 1.2

Comparison 1 Ergot derivatives versus placebo, Outcome 2 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days.

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Analysis 1.3

Comparison 1 Ergot derivatives versus placebo, Outcome 3 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days.

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Analysis 1.4

Comparison 1 Ergot derivatives versus placebo, Outcome 4 Rebound lactation.

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Analysis 2.1

Comparison 2 Oestrogen preparations versus placebo, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days.

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Analysis 2.2

Comparison 2 Oestrogen preparations versus placebo, Outcome 2 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days.

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Analysis 3.1

Comparison 3 Antioestrogen preparations versus placebo, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days.

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Analysis 3.2

Comparison 3 Antioestrogen preparations versus placebo, Outcome 2 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days.

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Analysis 4.1

Comparison 4 Pyridoxine versus placebo, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days.

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Analysis 5.1

Comparison 5 Combined oestrogen and androgen preparations versus placebo, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days.

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Analysis 6.1

Comparison 6 Androgen preparations versus placebo, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days.

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Analysis 7.1

Comparison 7 Pharmacologic treatment versus nonpharmacologic treatment, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain.

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Analysis 7.2

Comparison 7 Pharmacologic treatment versus nonpharmacologic treatment, Outcome 2 Rebound lactation.

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Analysis 8.1

Comparison 8 Comparison of two pharmacologic treatments, Outcome 1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days postpartum.

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Analysis 8.2

Comparison 8 Comparison of two pharmacologic treatments, Outcome 2 Rebound lactation.

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Analysis 8.3

Comparison 8 Comparison of two pharmacologic treatments, Outcome 3 Use of second line drug or method to achieve suppression of lactation.

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Analysis 8.4

Comparison 8 Comparison of two pharmacologic treatments, Outcome 4 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤14 days.

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Analysis 9.1

Comparison 9 High versus low dose quinestrol, Outcome 1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain at ≤ 7 days postpartum.

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Analysis 10.1

Comparison 10 Low versus high dose terguride, Outcome 1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain at days 0 ‐15.

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Analysis 10.2

Comparison 10 Low versus high dose terguride, Outcome 2 Side effect: dizziness.

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Analysis 11.1

Comparison 11 High versus low dose cabergoline, Outcome 1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain.

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Analysis 12.1

Comparison 12 Long course tamoxifen versus short course tamoxifen, Outcome 1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain at D0‐15.

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Comparison 1. Ergot derivatives versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days postpartum Show forest plot	3	107	Risk Ratio (IV, Fixed, 95% CI)	0.36 [0.24, 0.54]

1.1 Bromocriptine versus placebo	3	107	Risk Ratio (IV, Fixed, 95% CI)	0.36 [0.24, 0.54]
2 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days Show forest plot	2	76	Risk Ratio (IV, Random, 95% CI)	0.18 [0.03, 1.08]

2.1 Bromocriptine versus placebo	2	76	Risk Ratio (IV, Random, 95% CI)	0.18 [0.03, 1.08]
3 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days Show forest plot	1	32	Risk Ratio (IV, Fixed, 95% CI)	0.19 [0.07, 0.48]

3.1 Cabergoline versus placebo	1	32	Risk Ratio (IV, Fixed, 95% CI)	0.19 [0.07, 0.48]
4 Rebound lactation Show forest plot	1	40	Risk Ratio (IV, Fixed, 95% CI)	15.26 [1.01, 231.20]

Comparison 1. Ergot derivatives versus placebo

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Comparison 2. Oestrogen preparations versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days Show forest plot	7	971	Risk Ratio (IV, Random, 95% CI)	0.40 [0.29, 0.56]

1.1 Diethylstilbestrol versus placebo	4	376	Risk Ratio (IV, Random, 95% CI)	0.33 [0.12, 0.89]
1.2 Quinestrol versus placebo	3	342	Risk Ratio (IV, Random, 95% CI)	0.47 [0.30, 0.73]
1.3 Chlorotrianisene versus placebo	1	153	Risk Ratio (IV, Random, 95% CI)	0.51 [0.36, 0.73]
1.4 Hexestrol versus placebo	1	100	Risk Ratio (IV, Random, 95% CI)	0.41 [0.29, 0.57]
2 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days Show forest plot	2	103	Risk Ratio (IV, Random, 95% CI)	0.19 [0.03, 1.34]

Comparison 2. Oestrogen preparations versus placebo

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Comparison 3. Antioestrogen preparations versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days Show forest plot	1	30	Risk Ratio (IV, Fixed, 95% CI)	1.0 [0.51, 1.95]

1.1 Clomiphene versus placebo	1	30	Risk Ratio (IV, Fixed, 95% CI)	1.0 [0.51, 1.95]
2 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 14 days Show forest plot	1	140	Risk Ratio (IV, Fixed, 95% CI)	0.71 [0.62, 0.82]

2.1 Tamoxifen versus placebo	1	140	Risk Ratio (IV, Fixed, 95% CI)	0.71 [0.62, 0.82]

Comparison 3. Antioestrogen preparations versus placebo

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Comparison 4. Pyridoxine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days Show forest plot	2	258	Risk Ratio (IV, Fixed, 95% CI)	0.98 [0.89, 1.09]

1.1 Pyridoxine versus placebo	2	258	Risk Ratio (IV, Fixed, 95% CI)	0.98 [0.89, 1.09]

Comparison 4. Pyridoxine versus placebo

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Comparison 5. Combined oestrogen and androgen preparations versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days Show forest plot	3	436	Risk Ratio (IV, Fixed, 95% CI)	0.15 [0.10, 0.22]

1.1 Testosterone oenanthate + oestradiol valerate	3	436	Risk Ratio (IV, Fixed, 95% CI)	0.15 [0.10, 0.22]

Comparison 5. Combined oestrogen and androgen preparations versus placebo

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Comparison 6. Androgen preparations versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days Show forest plot	1	30	Risk Ratio (IV, Fixed, 95% CI)	1.13 [0.60, 2.11]

1.1 Testosterone propionate versus placebo	1	30	Risk Ratio (IV, Fixed, 95% CI)	1.13 [0.60, 2.11]

Comparison 6. Androgen preparations versus placebo

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Comparison 7. Pharmacologic treatment versus nonpharmacologic treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain Show forest plot	2		Risk Ratio (IV, Random, 95% CI)	Subtotals only

1.1 Bromocriptine versus any nonpharmacologic treatment	2	96	Risk Ratio (IV, Random, 95% CI)	0.31 [0.16, 0.61]
1.2 DIethylstibestrol versus any nonpharmacologic treatment	1	36	Risk Ratio (IV, Random, 95% CI)	0.19 [0.07, 0.49]
1.3 Oestradiol + testosterone esters versus any non pharmacologic treatment	1	36	Risk Ratio (IV, Random, 95% CI)	0.46 [0.28, 0.76]
1.4 Bendrofluazide versus any nonpharmacologic treatment	1	36	Risk Ratio (IV, Random, 95% CI)	0.68 [0.48, 0.94]
2 Rebound lactation Show forest plot	1	60	Risk Ratio (IV, Fixed, 95% CI)	5.0 [0.25, 99.95]

Comparison 7. Pharmacologic treatment versus nonpharmacologic treatment

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Comparison 8. Comparison of two pharmacologic treatments

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤ 7 days postpartum Show forest plot	12		Risk Ratio (IV, Random, 95% CI)	Subtotals only

1.1 Bromocriptine versus oestrogen preparations	4	340	Risk Ratio (IV, Random, 95% CI)	0.58 [0.25, 1.38]
1.2 Bromocriptine versus ergot derivative	3	228	Risk Ratio (IV, Random, 95% CI)	1.12 [0.37, 3.42]
1.3 Bromocriptine versus prostaglandins	1	43	Risk Ratio (IV, Random, 95% CI)	0.55 [0.19, 1.60]
1.4 Bromocriptine versus pyridoxine	1	97	Risk Ratio (IV, Random, 95% CI)	0.93 [0.75, 1.15]
1.5 Quinestrol versus other oestrogen preparations	3	208	Risk Ratio (IV, Random, 95% CI)	0.68 [0.32, 1.44]
2 Rebound lactation Show forest plot	4	149	Risk Ratio (IV, Fixed, 95% CI)	0.65 [0.39, 1.10]

2.1 Bromocriptine versus oestrogen preparations	2	67	Risk Ratio (IV, Fixed, 95% CI)	0.61 [0.34, 1.07]
2.2 Bromocriptine versus ergot derivative	1	39	Risk Ratio (IV, Fixed, 95% CI)	2.11 [0.43, 10.19]
2.3 Bromocriptine versus prostaglandins	1	43	Risk Ratio (IV, Fixed, 95% CI)	0.24 [0.03, 1.96]
3 Use of second line drug or method to achieve suppression of lactation Show forest plot	3		Risk Ratio (IV, Fixed, 95% CI)	Subtotals only

3.1 Bromocriptine versus oestrogen preparations	1	31	Risk Ratio (IV, Fixed, 95% CI)	0.31 [0.01, 7.15]
3.2 Bromocriptine versus ergot derivatives	1	40	Risk Ratio (IV, Fixed, 95% CI)	2.67 [0.82, 8.62]
3.3 Bromocriptine versus pyridoxine	1	97	Risk Ratio (IV, Fixed, 95% CI)	0.07 [0.01, 0.51]
4 Failure to suppress lactation as indicated by milk secretion, breast engorgement or breast pain at ≤14 days Show forest plot	6		Risk Ratio (IV, Random, 95% CI)	Subtotals only

4.1 Bromocriptine versus carbegoline	2	308	Risk Ratio (IV, Random, 95% CI)	1.38 [0.93, 2.05]
4.2 Bromocriptine versus diethylstilbestrol	1	38	Risk Ratio (IV, Random, 95% CI)	0.30 [0.07, 1.30]
4.3 Bromocriptine versus cyclofenil	1	24	Risk Ratio (IV, Random, 95% CI)	3.5 [0.16, 78.19]
4.4 Bromocriptine versus chlorotrianisene	1	39	Risk Ratio (IV, Random, 95% CI)	0.35 [0.19, 0.66]
4.5 Quinestrol versus other oestrogen preparations	1	99	Risk Ratio (IV, Random, 95% CI)	2.84 [1.56, 5.18]

Comparison 8. Comparison of two pharmacologic treatments

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Comparison 9. High versus low dose quinestrol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain at ≤ 7 days postpartum Show forest plot	1	132	Risk Ratio (IV, Fixed, 95% CI)	0.51 [0.33, 0.81]

1.1 Quinestrol 4 mg versus Quinestrol 2 mg	1	132	Risk Ratio (IV, Fixed, 95% CI)	0.51 [0.33, 0.81]

Comparison 9. High versus low dose quinestrol

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Comparison 10. Low versus high dose terguride

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain at days 0 ‐15 Show forest plot	1	45	Risk Ratio (IV, Fixed, 95% CI)	0.5 [0.29, 0.88]

1.1 Terguride 0.5‐1.0 mg vs terguride 0.25 mg	1	45	Risk Ratio (IV, Fixed, 95% CI)	0.5 [0.29, 0.88]
2 Side effect: dizziness Show forest plot	1	45	Risk Ratio (IV, Fixed, 95% CI)	1.55 [0.07, 35.89]

2.1 Terguride 0.5‐1.0 mg vs terguride 0.25 mg	1	45	Risk Ratio (IV, Fixed, 95% CI)	1.55 [0.07, 35.89]

Comparison 10. Low versus high dose terguride

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Comparison 11. High versus low dose cabergoline

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain Show forest plot	1	80	Risk Ratio (IV, Fixed, 95% CI)	0.14 [0.03, 0.59]

Comparison 11. High versus low dose cabergoline

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Comparison 12. Long course tamoxifen versus short course tamoxifen

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to suppress lactation as described by milk secretion, breast engorgement or breast pain at D0‐15 Show forest plot	1	65	Risk Ratio (IV, Fixed, 95% CI)	0.75 [0.61, 0.92]

1.1 Tamoxifen (14 days course) vs tamoxifen (6 days course)	1	65	Risk Ratio (IV, Fixed, 95% CI)	0.75 [0.61, 0.92]

Comparison 12. Long course tamoxifen versus short course tamoxifen

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