Difficult conversations: Management of estradiol deficiency

“Impact of hormone therapy on the bone density of women with premature ovarian insufficiency: A systematic review” by Costa et al. [ ] is a call for action, i.e., education and advocacy. What is the first-line hormone therapy for primary ovarian insufficiency (POI) supported by the best evidence? Women with POI have low bone mineral density. Inadequate therapy fails to remedy this. A recent report in the New York Times, “Women have been misled about menopause,” [ ] demonstrates that shared decision making remains a difficult conversation [ ]. Women younger than 45 with estradiol deficiency have a metabolic derangement associated with increased morbidity and mortality [ ]. Generally, prospective, double-blind, controlled trials are considered the highest level of evidence for therapeutic studies [ ]. The authors found only one such study in their review of 335 reports. The only double-blind, controlled trial, conducted by the US National Institutes of Health (NIH) [ ], provided the average daily production rate of estradiol (100 micrograms per day) by transdermal patch and monthly, cyclic, oral progestogen. The NIH hormone regimen restored bone mineral density to normal over three years and was well tolerated. There is evidence that oral estrogen treatment has a higher risk of thromboembolism than transdermal estradiol replacement, yet this more physiologic approach is underutilized in clinical practice [ ]. Currently the best evidence supports the NIH regimen of replacement estradiol in young women using the 100 microgram dose delivered by the transdermal route. Future research should build on this hard evidence rather than from a standpoint of equipoise.