Estradiol use while Breastfeeding
Drugs containing Estradiol: Estrace, Vagifem, Estrace Vaginal Cream, Vivelle-Dot, Minivelle, Climara, Activella, Estring, Estradiol Patch, Estrogel, Show all 107 »Progynova, Vivelle, Estrogen Patches, CombiPatch, Mimvey, Divigel, Angeliq, Estrofem, Delestrogen, Ena, Natazia, Femring, Alora, Depo-Estradiol, Evamist, Lopreeza, Mimvey Lo, Elestrin, Esclim, Prefest, Climara Pro, Menorest, Estra-C, Oestrodose, Fematrix, Lunelle, Estraderm, Systen, FemTab, Oestradiol Implants, Delidose, Estreva, Climaval, Nuvelle TS Phase I, Fempatch, Estradot 37.5, Estradot 50, Oestrogel, Estrasorb, Menostar, Oromone, Provames, Thaissept, Femsept, Thais, Estradiol G GAM, Organon Oestradiol, Bedol, Dermestril Septem, Femtrace, Estrapatch, Dura-Dumone, Duratestrin, Depotestogen, Depo-Testadiol, Ortho-Prefest, Dep Androgyn, Delatestadiol, Duo-Cyp, Valertest No 1, Estra-Testrin, Climodien, Clinagen LA 40, Medidiol 10, Estro-Span 40, Gynodiol, Dura-Estrin, Estragyn LA 5, Estro-LA, Oesclim, Estro-Cyp, Estra-V 40, Dep Gynogen, Depogen, Valergen, Gynogen LA 20, Dioval 40, Duragen, Dioval XX, Menaval-20, Estradot, Zumenon, Elleste Solo, Sandrena, Adgyn Estro, FemSeven Sequi Phase I, Femtran, Menorest Patch, Aerodiol, Progynova TS, Estradot 100, Estradot 75, Oestrogel Pump-Pack, Dermestril, FemSeven, Evorel, Primogyn Depot
Estradiol Levels and Effects while Breastfeeding
Summary of Use during Lactation
Limited information on the use of estradiol during breastfeeding indicates that the route of administration and dosage form have influences on the amount transferred into breastmilk. Vaginal administration results in measurable amounts in milk, but transdermal patches do not. Maternal doses of up to 200 mcg daily transdermally do not increase estradiol or estriol in breastfed infants or cause any adverse effects in breastfed infants. Vaginal administration results in unpredictable peak times for estradiol in breastmilk, so timing of the dose with respect to breastfeeding is probably not useful.
A case report of inadequate milk production and inadequate infant weight gain was possibly caused by transdermal estradiol initiated on the first day postpartum, but 2 small studies found no such effect when the drug was initiated after lactation was well established.
Maternal Levels. Six women who were 6 or more months postpartum were given a vaginal suppository containing 50 or 100 mg of estradiol. In 3 of the 6 women, peak milk levels occurred 3 hours after the dose. In 2 others, the peak level occurred 7 hours after the dose and in the sixth, the peak occurred 11 hours after the dose. Peak milk levels were about 100 ng/L in 4 women, in one it was 300 ng/L and in the sixth, it was 1000 ng/L.
Twenty-one women who were 20 weeks postpartum and breastfeeding their infants were randomized to receive a transdermal patch that released estradiol 50 mcg (n = 7), 75 mcg (n = 5) or 100 mcg (n = 6) daily or placebo (n = 4) for 2 weeks. Breastmilk and serum samples were collected at the beginning and end of the study. Serum estradiol levels increased slightly from baseline, but the differences were not statistically significant; serum levels were in the range of 25 to 45 ng/L. Estradiol was undetectable (<6.8 ng/L) in all breastmilk samples.
Infant Levels. Six nursing mothers received transdermal estradiol as part of a study comparing estradiol to sertraline and placebo for postpartum depression. The mothers received estradiol dosages between 50 and 200 mcg daily (mean 133 mcg daily) at the time of serum level analysis at 4 and 8 weeks of therapy. Four of the 6 infants were exclusively breastfed and the other two were more than 50% breastfed. All infants had undetectable (<2.5 ng/L) serum estriol concentrations and 4 of the 6 had undetectable (<2.5 ng/L) serum estradiol concentrations. The other two had estradiol concentrations of 7 and 7.1 ng/L. The serum estriol and estradiol concentrations were not significantly different from breastfed infants in the placebo or sertraline arms of the study. No correlation was found between maternal and infant serum concentrations of estriol or estradiol.
Effects in Breastfed Infants
A mother who had severe postpartum depression with 2 previous infants was prescribed a transdermal estradiol patch that released 50 mcg daily beginning on day 1 postpartum to prevent recurrence of depression. At 11 days of age, the infant was jaundiced and had gained only 60 grams since birth. With more frequent nursing, weight gain improved, but remained inadequate until day 28 when the estradiol was discontinued. The infant then experienced above average weight gain through day 66 postpartum. The delayed and reduced weight gain was possibly caused by estradiol.
Six nursing mothers received transdermal estradiol as part of a study comparing estradiol to sertraline and placebo for postpartum depression. The mothers received estradiol dosages between 50 and 200 mcg daily (mean 133 mcg daily) at the time of serum level analysis at 4 and 8 weeks of therapy. Four of the 6 infants were exclusively breastfed and the other two were more than 50% breastfed. There was no difference in infant length, weight, and head circumference nor in the average daily gains in any of these parameters between treatments.
Effects on Lactation and Breastmilk
Thirteen women who were 12 weeks postpartum and fully breastfeeding their infants were given a transdermal patch that released 100 mcg of estradiol daily. The average number of breast feeds per day did not change significantly during 3 days of patch application.
Nineteen women who were 6 weeks postpartum, using a barrier contraceptive method and breastfeeding their infants were randomized to transdermal patches that released estradiol 50 mcg daily or placebo patches for 12 weeks. An additional control group received no patches. The number of breast feeds per day decreased in all groups over the course of the study, but there were no important differences among the groups.
A retrospective cohort study compared 371 women who received high-dose estrogen (either 3 mg of diethylstilbestrol or 150 mcg of ethinyl estradiol daily) during adolescence for adult height reduction to 409 women who did not receive estrogen. No difference in breastfeeding duration was found between the two groups, indicating that high-dose estrogen during adolescence has no effect on later breastfeeding.
Alternate Drugs to Consider
1. Nilsson S, Nygren KG, Johansson ED. Transfer of estradiol in human milk. Am J Obstet Gynecol. 1978;132:653-7. PMID: 717472
2. Perheentupa A, Ruokonen A, Tapanainen JS. Transdermal estradiol treatment suppresses serum gonadotropins during lactation without transfer into breast milk. Fertil Steril. 2004;82:903-7. PMID: 15482766
3. Pinheiro E, Bogen DL, Hoxha D, Wisner KL. Transdermal estradiol treatment during breastfeeding: maternal and infant serum concentrations. Arch Womens Ment Health. 2015. PMID: 25956588
4. Ball DE, Morrison P. Oestrogen transdermal patches for post partum depression in lactating mothers--a case report. Central Afr J Med. 1999;45:68-70. PMID: 10565065
5. Illingworth PJ , Seaton JEV et al. Low dose transdermal oestradiol suppresses gonadotrophin secretion in breast-feeding women. Hum Reprod. 1995;10:1671-7. PMID: 8582959
6. Perheentupa A, Critchley HOD, Illingworth PJ et al. Enhanced sensitivity to steroid-negative feedback during breast-feeding: low-dose estradiol (transdermal estradiol supplementation) suppresses gonadotropins and ovarian activity assessed by inhibin B. J Clin Endocrinol Metab. 2000;85:4280-6. PMID: 11095468
7. Jordan HL, Bruinsma FJ, Thomson RJ et al. Adolescent exposure to high-dose estrogen and subsequent effects on lactation. Reprod Toxicol. 2007;24:397-402. PMID: 17531440
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