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Reviewed by Ovidio Bermudez, MD, FAAP, FSAHM, FAED, F.iaedp, CEDS

Ackerman, K. E., Singhal, V., Baskaran, C., Slattery, M., Campoverde Reyes, K. J., Toth, A., . . . Misra, M. (2018). Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial. British Journal of Sports Medicine, 53(4), 229.

https://doi.org/10.1136/bjsports-2018-099723

Individuals with eating disorders that involve caloric restriction, over exercise and low weight state and thus have insufficient energy availability (EA) can suffer from a variety of medical complications that include low bone mineral density (LBMD) and increased risk of fractures.  Hypogonadotropic hypogonadism seems to be part of the pathogenesis both in underweight patients as well as in normal weight athletes with female/male athlete triad.  Several studies have made it clear that oral contraceptive pills or other forms of oral estrogen/progesterone replacement do not improve LBMD.  Some more recent studies have reported that transdermal estrogen/progesterone replacement may be of benefit due to bypassing first-pass by the liver among other mechanisms.  Normal weight athletes can also have their bone health affected by low EA specially if they experience oligo-amenorrhea (OAA).  The purpose of this 3-arm study was to compare the response over 12 months of estrogen/progesterone administered trans dermally, orally, or no hormone administration.

121 female athletes between the ages of 14 and 25 years with no differences in baseline characteristics such as weight, BMI, lean or fat body mass were included.  Baseline DXA bone scan were repeated at 6 and 12 months.  73 subjects completed the study.   They were assigned to 3 arms.  The first arm received physiological estrogen replacement via 100 mcg transdermal 17 β E2 applied twice weekly and cyclic micronized progesterone 200 mgs for 12 days each month (PATCH).  The second arm received an oral contraceptive containing 30 mcg of ethynyl estradiol and 0.15 mg of desogestrel (PILL).  The third arm did not receive any estrogen or progesterone (NONE).  All 3 received calcium and Vitamin D supplementation.  The conclusion was that transdermal estrogen over 12 months improves BMD in athletes with OAA, especially compared to oral contraceptive pills containing ethynyl estradiol.

Why is this important?

This study adds another piece of evidence to our understanding that hypogonadotropic hypogonadism is a consequence of long-standing insufficient EA and pivotal to the complication of LBMD.  Oral testosterone replacement is helpful to improve BMD in men.  Estrogen replacement in a bioavailable fashion (trans dermally) may also improve BMD in females.  This applies to both underweight individuals suffering from an eating disorder and normal weight athletes with OAA.  The key lesson is to continue research to better understand how effective delivery of a pharmacologic agent may make a difference to not to dismiss interventions due to our lack of understanding of how to best deliver or apply.

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