Is Promone-E Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use Promone-E? Is Promone-E safe for nursing mother and child? Does Promone-E extracts into breast milk? Does Promone-E has any long term or short term side effects on infants? Can Promone-E influence milk supply or can Promone-E decrease milk supply in lactating mothers?

Synthetic progestin similar to progesterone that is used in uterine bleeding, dysmenorrhea, infertility and contraception.For contraception is used as a single drug or in combination with estrogen (e.g. Estradiol + Medroxyprogesterone).For oral use or long-acting injectable administration (Intramuscular or subcutaneous). It is excreted into breast milk in clinically non-significant amount, and, no problems have been observed in infants whose mothers who were treated with this medication. Plasma levels of these infants were undetectable or very low.There may be increased prolactin and milk production in women who receive medroxyprogesterone. Although it has not been shown effects on production and duration of breastfeeding when administered at any time postpartum, it is still controversial on if it really decreases milk production when progestins are used before a fully establishment of breastfeeding has occurred. Therefore, experts’ protocols by WHO and ABM advise to avoiding it until breastfeeding is fully developed (4-6 weeks). During lactation progestin-only drugs are preferred or in combination with estrogen for birth control, but whatever, the ones with the lower doses of estrogen should be used.For the first 6 weeks postpartum, non-hormonal methods are of choise. Hormone containing contraceptives do not affect the composition of milk, minerals (Mg, Fe, Cu, Ca, P) fat, lactose and calories but only a few the proteins. WHO List of Essential Medicines 2002: rates it as compatible with breastfeeding after the 6th postnatal week.

Although nonhormonal methods are preferred during breastfeeding, progestin-only contraceptives such as depot Promone-E (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.[1][2][3][4] Some evidence indicates that progestin-only contraceptives may offer protection against bone mineral density loss during lactation, or at least do not exacerbate it.[5][6][7] The timing of initiation of DMPA is controversial.[8] 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.[9] A subsequent study raised the possibility of a slight reduction in breastfeeding duration in women given DMPA before hospital discharge,[10] and another study found that breastfeeding was less like to be initiated if mothers received immediate postpartum DMPA.[11] 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.[12]The World Health Organization recommends that injectable depot Promone-E should not used before 6 weeks postpartum.[13]

In a nonrandomized study, 228 women chose depot Promone-E 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.[17] 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.[18] A multicenter, nonrandomized study followed 541 infants whose mothers received depot Promone-E 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.[19][20] Thirteen male breastfed infants whose mothers received 150 mg of Promone-E 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.[16] 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.[21] 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.[22] 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 Promone-E injection at 6 weeks postpartum (n = 20). No difference in infant weight gain was noted between the two groups.[23] One-hundred-fifty mothers were given 150 mg of depot Promone-E 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.[24]

Galactorrhea has been reported in nonpregnant, nonlactating women using depot Promone-E (DMPA). In one case series, 3.6% of 360 adolescents who used depot Promone-E as a contraceptive for at least 6 months developed galactorrhea with normal prolactin levels.[25] Numerous studies found that the use of intramuscular depot Promone-E 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.[17][19][21][22][26][27][28][29][30][31][32] However, most of these were so seriously flawed that no valid conclusion can be drawn on the effect of early initiation on breastfeeding duration.[9] Twenty-five women who were 6 weeks postpartum were given a single injection of 150 mg of depot Promone-E. 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.[33] Women (n = 80) were assigned randomly to receive intramuscular depot Promone-E (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.[34] A nonrandomized, nonblinded study compared women who received either nonhormonal contraception (n = 56) or depot Promone-E (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.[35] In a nonrandomized, nonblinded study comparing women who were breastfeeding at discharge, 102 postpartum women received depot Promone-E (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.[36] 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.[10] One-hundred-fifty mothers were given 150 mg of depot Promone-E 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).[24] 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.[37]