毒理性
哺乳期使用总结：尽管在哺乳期首选非激素方法，但仅含孕激素的避孕药，如庚酸美诺孕酮（DMPA）被认为是哺乳期所有阶段的激素避孕药的首选。质量合理的证据表明，DMPA不会对乳汁的成分、婴儿的生长发育或乳汁供应产生不利影响。一些证据表明，仅含孕激素的避孕药可能对防止哺乳期间骨矿物质密度丢失提供保护，或者至少不会加剧这种情况。
DMPA开始使用的时间存在争议。产品标签指出，根据提交产品批准的数据，应在分娩后至少6周开始使用。质量合理的研究表明，对于婴儿立即产生不良影响的担忧是没有根据的；然而，理论上如果开始得太早，由于新生儿对药物的代谢较慢，可能会对新生儿产生不利影响。令人担忧的是，目前还没有数据表明孕激素对这个年龄的大脑和肝脏发育的影响。分娩后6周内使用可能会干扰哺乳的专一性或持续时间。对使用早期产后DMPA的研究的系统回顾发现，所有的研究质量都很低，不足以证明如果分娩后6周内给予DMPA，对乳汁生产的担忧是没有根据的。随后的一项研究发现，与出院前接受DMPA的妇女相比，哺乳期持续时间略有缩短，另一项研究发现，如果母亲在产后立即接受DMPA，她们不太可能开始哺乳。
美国的专家意见认为，仅含孕激素的避孕产品的风险通常对于任何时间段的哺乳母亲是可以接受的。世界卫生组织建议，不应在分娩后6周内使用注射用庚酸美诺孕酮。
对哺乳婴儿的影响：在一项非随机研究中，228名妇女选择在产后2至4个月开始每3个月注射一次庚酸美诺孕酮作为避孕方法。88%的妇女至少哺乳了6个月。在研究期间和婴儿4.5岁时再次检查，未发现暴露婴儿的生长发育有不良影响。
对1215名在哺乳期间接受庚酸美诺孕酮的母亲所生子女的随访研究发现，青春期女孩（由母亲报告）的阴毛出现延迟，但男孩则没有。在对社会经济地位进行校正后，未观察到其他生长影响。
在一项多中心、非随机研究中，跟踪了541名其母亲在哺乳期间每3个月接受一次150mg庚酸美诺孕酮醋酸酯注射的婴儿。与标准测量相比，未发现对婴儿第一年的生长有不利影响。
对13名在产后6周和18周接受150mg美诺孕酮醋酸酯肌注的哺乳期男婴进行了研究。与对照组的9名对照婴儿相比，血清黄体生成素、卵泡刺激素、未结合睾酮或皮质醇的水平没有差异。
在一项非随机研究中，比较了190名使用庚酸美诺孕酮的妇女所生的婴儿与大约57天产后开始使用非激素避孕或没有避孕的妇女所生的婴儿，无论婴儿是完全哺乳还是部分哺乳，从出生到6个月大的婴儿生长速度没有差异。
在一项对270名接受产后DMPA的婴儿的回顾性队列研究中，调整了混杂因素后，DMPA对体重没有影响，两组在心理运动发展、里程碑、健康问题、婴儿身高或体格检查方面没有差异。
在一项非盲法、随机研究中，比较了那些在分娩后24-48小时接受依托孕烯植入物（n = 20）的完全哺乳妇女和那些在分娩后6周接受150mg庚酸美诺孕酮醋酸酯注射的妇女（n = 20）。两组之间婴儿体重增加没有差异。
150名母亲在哺乳建立后、出院前2至10天内接受了150mg庚酸美诺孕酮醋酸酯肌注，3个月后再次给药。在一项病例对照研究中，将他们的婴儿的生长（身高和体重）和疾病与对照组进行了比较。在产后1.5、3和6个月时，两组之间没有差异。注射给药的产后时间对结果没有影响。
对哺乳和乳汁的影响：在使用庚酸美诺孕酮醋酸酯（DMPA）作为非孕妇、非哺乳妇女的避孕药时，报告了乳汁分泌过多的情况。在一项病例系列中，360名使用庚酸美诺孕酮醋酸酯作为避孕药至少6个月的青少年中，有3.6%出现了正常催乳素水平的乳汁分泌过多。
许多研究发现，在分娩后7天或更晚开始使用肌注庚酸美诺孕酮醋酸酯作为避孕药，要么对哺乳没有负面影响，要么会增加乳汁供应、哺乳持续时间或乳汁质量。然而，这些研究大多存在严重缺陷，无法对早期开始对哺乳持续时间的影响得出有效结论。
25名产后6周的妇女接受了单次150mg庚酸美诺孕酮醋酸酯注射。将她们的血清催乳素水平与使用宫内节育器的25名妇女进行了比较。所有妇女都以大致
◉ Summary of Use during Lactation:Although nonhormonal methods are preferred during breastfeeding, progestin-only contraceptives such as depot medroxyprogesterone acetate (DMPA) are considered the hormonal contraceptives of choice during all stages of lactation. Fair quality evidence indicates that DMPA does not adversely affect the composition of milk, the growth and development of the infant, or the milk supply. Some evidence indicates that progestin-only contraceptives may offer protection against bone mineral density loss during lactation, or at least do not exacerbate it.
The timing of initiation of DMPA is controversial. The product labeling states that it should be started no sooner than 6 weeks postpartum, based on data submitted for product approval. Studies of fair quality seem to indicate that concerns about immediate adverse effects on the infants is unfounded; however, starting too soon theoretically could affect the newborn infant adversely because of slower metabolism of the drug than older infants. Of concern is that no data exist on the effects of progesterone on brain and liver development at this age. Administration sooner than 6 weeks postpartum could interfere with the exclusivity or duration of lactation. A systematic review of studies using early postpartum initiation of DMPA concluded that all of the studies were of low quality and inadequate to disprove the concern about DMPA's effects on milk production if given sooner than 6 weeks after delivery. A subsequent study raised the possibility of a slight reduction in breastfeeding duration in women given DMPA before hospital discharge, and another study found that breastfeeding was less like to be initiated if mothers received immediate postpartum DMPA.
Expert opinion in the United States holds that the risks of progestin-only contraceptive products usually are acceptable for nursing mothers at any time postpartum. The World Health Organization recommends that injectable depot medroxyprogesterone acetate should not be used before 6 weeks postpartum.
◉ Effects in Breastfed Infants:In a nonrandomized study, 228 women chose depot medroxyprogesterone acetate injection every 3 months as a postpartum contraceptive starting in months 2 to 4 postpartum. Eighty-eight percent of the women breastfed their infants for at least 6 months. Infants were examined during the study and again at age 4.5 years. No adverse effects on infant growth and development were noted in the exposed infants.
One follow-up study of 1215 children whose mothers received depot medroxyprogesterone during nursing reported a delayed appearance of pubic hair (reported by mothers) in pubescent girls, but not boys. No other effects on growth were observed after correction for socioeconomic status.
A multicenter, nonrandomized study followed 541 infants whose mothers received depot medroxyprogesterone acetate injection 150 mg every 3 months for contraception during breastfeeding. No adverse effects on infant growth through the first year were found in comparison to standard measurements.
Thirteen male breastfed infants whose mothers received 150 mg of medroxyprogesterone acetate intramuscularly at weeks 6 and 18 postpartum were studied. No differences were found in serum levels of luteinizing hormone, follicle-stimulating hormone, unconjugated testosterone, or cortisol compared to those of a group of 9 control infants.
In a nonrandomized study comparing 190 infants of women using depot medroxyprogesterone to those using a nonhormonal contraceptive or no contraception starting at about day 57 postpartum, no difference in infant growth rates were seen from birth to 6 months of age, regardless of whether the infant was fully or partially breastfed.
In a retrospective cohort study of 270 infants whose mothers were given DMPA postpartum, no effect of DMPA on weight when adjusted for cofounders and no differences between groups in psychomotor development, milestones, health problems, infant height or physical examinations.
A non-blinded, randomized study of exclusively breastfeeding women compared those who received an etonogestrel implant 24-48 hours after delivery (n = 20) to those who received a 150 mg depot medroxyprogesterone acetate injection at 6 weeks postpartum (n = 20). No difference in infant weight gain was noted between the two groups.
One-hundred-fifty mothers were given 150 mg of depot medroxyprogesterone acetate intramuscularly after breastfeeding was established postpartum, but before discharge at 2 to 10 days; a second dose was given at 3 months postpartum. The growth (height and weight) and illnesses of their infants was compared to those of a control group in a case-control study. No difference between the groups was seen at 1.5, 3 and 6 months postpartum. The day postpartum when the injection was given had no effect on the outcome.
◉ Effects on Lactation and Breastmilk:Galactorrhea has been reported in nonpregnant, nonlactating women using depot medroxyprogesterone acetate (DMPA). In one case series, 3.6% of 360 adolescents who used depot medroxyprogesterone acetate as a contraceptive for at least 6 months developed galactorrhea with normal prolactin levels.
Numerous studies found that the use of intramuscular depot medroxyprogesterone acetate as a contraceptive beginning at 7 days postpartum or later either has no negative effect or causes increases in the milk supply, duration of lactation or quality of breastmilk. However, most of these were so seriously flawed that no valid conclusion can be drawn on the effect of early initiation on breastfeeding duration.
Twenty-five women who were 6 weeks postpartum were given a single injection of 150 mg of depot medroxyprogesterone acetate. Serum prolactin levels were compared to those of 25 women who used an IUD. All women breastfed their infants to about the same extent. Basal serum prolactin levels were similar between the groups at the beginning of the study. These levels slowly decreased in the IUD group, but increased in the medroxyprogesterone group. The differences were statistically significant at 6 weeks after the start of the study. Basal prolactin increases in the medroxyprogesterone were 14% over baseline and 59% over the IUD group at 6 weeks.
Women (n = 80) were assigned randomly to receive intramuscular depot medroxyprogesterone acetate (DMPA) 250 mg 1 to 2 days postpartum. Other women in the study (n = 616) were started on DMPA at 30 days postpartum. The median duration of lactation in both groups was longer in these women than the lactation duration following previous births.
A nonrandomized, nonblinded study compared women who received either nonhormonal contraception (n = 56) or depot medroxyprogesterone acetate (n = 47) 150 mg intramuscularly upon discharge from the hospital. No statistical differences were found in the breastfeeding rates or percentage of women exclusively breastfeeding between the 2 groups of women at 1, 4, 8, 12 or 16 weeks postpartum.
In a nonrandomized, nonblinded study comparing women who were breastfeeding at discharge, 102 postpartum women received depot medroxyprogesterone acetate (dosage not stated) in the early postpartum period (average 51.9 hours postpartum; range 6.25 to 132 hours), 181 received another progestin-only contraceptive and 138 used nonhormonal contraception. No differences in breastfeeding rates were seen at 2 and 6 weeks, but women receiving any hormonal contraceptive were breastfeeding at a lower rate (72.1% vs 77.6%) at 4 weeks postpartum. The authors concluded that progestin-only contraception initiated in the early postpartum period had no adverse effects on breastfeeding rates.
A survey of 183 women who delivered in one hospital compared those who received DMPA after delivery and prior to discharge (n = 68) to those who did not receive the treatment (n = 115). There was a slight, but not statistically significant reduction in the duration of lactation among the mothers who received the early DMPA.
One-hundred-fifty mothers were given 150 mg of depot medroxyprogesterone acetate intramuscularly after breastfeeding was established postpartum, but before discharge at 2 to 10 days; a second dose was given at 3 months postpartum. In a case-control study these mothers were compared to a control group of women receiving no postpartum contraception. No difference was found between the groups in the number of nursings per day over the 6-month follow-up period, nor was there a difference in patient satisfaction in multiparous mothers compared to previous breastfeeding experience(s).
Women who delivered at two teaching hospitals in South Africa were randomized to receive either DMPA or an IUD within 48 hours of childbirth. There were no differences in exclusive or partial breastfeeding rates between the DMPA and IUD users at baseline or at 1 and 3 months postpartum.
A secondary analysis of a study on postpartum mothers analyzed mothers who did (n = 29) or did not (n = 141) receive depot medroxyprogesterone after delivering an infant of 32 weeks or less of gestational age and weighing 1500 grams or less. The analysis found no differences in milk production on days 1–7, 14, or 21 or on duration of lactation between the two groups.
来源:Drugs and Lactation Database (LactMed)
