The value of transdermal estrogen treatment postpartum

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Authors:

Alison Shea, MD, PhD, FRCSC

Mature Women’s Health Program 
University of Toronto,
Mount Sinai Hospital, Toronto

Abstract:

The management of women with premature ovarian insufficiency (POI) requires a comprehensive approach to all health concerns. Caring for these women following a successful pregnancy, either spontaneously or with advanced reproductive technologies poses additional challenges for the clinician. A recent submission concerning the management of these patients suggested that hormone replacement should be avoided when breastfeeding.  The aim of this paper is to oppose this idea. We suggest that optimal management in the early postpartum period involves hormone replacement for protection of mood and maintenance of circulating hormone levels. 

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It was recently suggested that women with premature ovarian insufficiency (POI) should be advised “not to use HRT, including contraceptive steroids, until she has completely weaned her child” (1).  The author advised against the use of hormone therapy in the postpartum period as it may cause neonatal breast enlargement, while also negatively influencing breastfeeding. The references cited to substantiate these claims were unfortunately based on much older sources from 1978 (2) and 1984 (3) that were focused on the combined oral contraceptive (COC) pill in postpartum women.  The latter reference examined the effects of a COC pill with 30 micrograms of ethinyl estradiol on milk volume and did find a reduction, as compared to progesterone only pills and placebo.  One additional commentary article was mentioned from 1996, but again, was discussing COC and not transdermal hormone therapy (4).  We propose that transdermal estradiol treatment, when needed for certain groups of women postpartum, such as those with POI, postpartum depression, or with a history of premenstrual dysphoric disorder (PMDD) may benefit from using transdermal estrogen. 

It was previously thought that estradiol treatment may affect milk supply based on a single case report (5), but newer information challenges this idea.  In women who were given transdermal estrogen with doses ranging from 50-100 micrograms per day for 2 weeks, there was no measurable estradiol level from their breast milk.  This challenges the suggestions that maternal estradiol use may cause neonatal breast development (6).  Recently Pinhero and colleagues (7) administered estradiol to women for 8 weeks in total (50-100 microgram patch/ day) and found no correlation between maternal and infant serum concentrations of either estrone or estradiol (7).  To investigate any possible effect on the amount or quality of the breast milk produced they measured infant growth.  There were no differences in infant growth outcomes (length, weight, head circumference or daily weight gain) when comparing women treated with estradiol versus sertraline or placebo.   This finding may lend reassurance to women who may need this therapy for their well-being.    

A timely systematic review from 2016 showed that among infants born to women who initiate the COC at 6 weeks postpartum or later, there is no difference in growth or health when compared to the unexposed (8).  When considering a combined oral contraceptive (COC) pill in the postpartum period, it may be prudent to wait until 6 weeks when the risk for venous thrombus embolism (VTE) is reduced.  Further, a COC with the lowest dose of ethinyl estradiol (for example 20 micrograms) would likely decrease any potential negative effects on milk volume.  The American College of Obstetricians and Gynecologists (ACOG) suggests that if desired, a COC may be initiated once breastfeeding has been established (9). 

The estradiol levels in the available transdermal estradiol preparations used for hormone replacement in POI are much lower than that contained in a COC. Further, the transdermal approach avoids the first pass metabolism of the liver, which decreases the risk for VTE.  Treatment with estradiol may be helpful for women who are sensitive to the rapidly changing hormone levels during the postpartum period.  There is a complex interconnection between estradiol and serotonin, but not all women are affected equally during the postpartum period.  In fact, it has proven difficult to predict postpartum depression by measuring estradiol levels alone.  Rather, women with postpartum depression show a genetic vulnerability to estrogen signaling pathways (10).   A study of severely depressed women showed rapid improvement in mood when treated with transdermal estradiol, with significant improvement even after one week (11).  It has been proposed that decreasing estradiol levels may negatively affect the regulation of serotonin, and thereby influence affect regulation among women during times of increased vulnerability.  This rapid decline of estradiol levels in the early postpartum period is likely even more profound among women with POI.  This complex interplay between estrogen and serotonergic function is important for clinicians to appreciate when caring for women with a failure of endogenous ovarian function. 

References:

1. Sullivan SD, Sarrel PM, & Nelson LM (2016) Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril 106(7):1588-1599.
2. Anonymous (1978) Which pill to choose in breastfeeding. in Fam Plan Inf Serv, p 1:17.
3. Tankeyoon M, et al. (1984) Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives. Contraception 30(6):505-522.
4. Kelsey JJ (1996) Hormonal contraception and lactation. J Hum Lact 12(4):315-318.
5. Ball DE & Morrison P (1999) Oestrogen transdermal patches for post partum depression in lactating mothers--a case report. Cent Afr J Med 45(3):68-70.
6. Perheentupa A, Ruokonen A, & Tapanainen JS (2004) Transdermal estradiol treatment suppresses serum gonadotropins during lactation without transfer into breast milk. Fertil Steril 82(4):903-907.
7. Pinheiro E, Bogen DL, Hoxha D, & Wisner KL (2016) Transdermal estradiol treatment during breastfeeding: maternal and infant serum concentrations. Archives of women's mental health 19(2):409-413.
8. Tepper NK, Phillips SJ, Kapp N, Gaffield ME, & Curtis KM (2016) Combined hormonal contraceptive use among breastfeeding women: an updated systematic review. Contraception 94(3):262-274.
9. ACOG clinical practice guideline. Use of Hormonal Contraception in Women with Coexisting Medical Conditions. Obstetrics and Gynecology 73: 1-20.
10. Mehta D, et al. (2014) Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling. Psychol Med 44(11):2309-2322.
11. Ahokas A, Kaukoranta J, Wahlbeck K, & Aito M (2001) Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. J Clin Psychiatry 62(5):332-336.


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