{"paper_id":"ad62d9f0-00e8-441b-89d9-4f589fe0417c","body_text":"Examining the EVIDENCE\nFAST  \nTRACK\nmdedge.com/obgyn V ol. 32  No. 11  |   November 2020   |   OBG Management   17\nAlthough HT is \na mainstay of \ntreatment for \nwomen with POI, \nit is uncertain  \nwhich approach  \nto HT is most \neffective in terms\n \nof bone mineral \ndensity\nWhich hormonal management  \napproach for women with premature \novarian insufficiency is best for bone?\nThe use of combined oral contraceptives (COCs) \nin 119 women with a mean age of 30.3 years \nwho had premature ovarian insufficiency was \nassociated with the most positive trends in \nbone mineral density (BMD).\n Bone density scans \nrevealed that women who used COC or high-dose estrogen \nplus progesterone therapy (EPT) had increases in BMD at \nthe lumbar spine, while women who used no treatment or \nlow-dose EPT experienced declines in lumbar spine BMD.\nCarvalho Gazarra LB, Bonacordi CL, Yela DA, et al. Bone \nmass in women with premature ovarian insufficiency: a \ncomparative study between hormone therapy and com-\nbined oral contraceptives. Menopause. 2020;27:1110-1116.\nEXPERT COMMENTARY\nAndrew M. Kaunitz, MD,  is Professor and  \nAssociate Chairman, Department of Obstetrics and \nGynecology, University of Florida College of Medi-\ncine–Jacksonville; Medical Director and Director  \nof Menopause and Gynecologic Ultrasound Ser -\nvices, UF Women’s Health Specialists at Emerson,  \nJacksonville. He serves on the OBG M\nanagement \nBoard of Editors.\nP\nremature ovarian insufficiency (POI) \nrefers to a condition in women in \nwhom ovarian function ceases prior \nto age 40 years. Although hormone therapy \n(HT) is a mainstay of treatment for women \nwith POI, it is uncertain which approach to \nHT is most effective in terms of bone mineral \ndensity (BMD). Investigators recently pub -\nlished their results of an observational study \nth\nat aimed to evaluate the use of combined \noral contraceptives (COCs) for preserving \nBMD in women with POI.\nDetails of the study\nAt an academic center in Brazil, Carvalho \nGazarra and colleagues identified women \nwith POI who had undergone 2 or more \nBMD assessments performed 2 or more \nyears apart.\n1 HT regimens (all of which were \ntaken continuously) employed the follow -\ning: a COC with ethinyl estradiol (EE) 30 µg \nand le\nvonorgestrel; low-dose estrogen plus \nprogestin therapy (EPT , conjugated equine \nestrogen [CEE] 0.625 mg with medroxypro -\ngesterone acetate or estradiol 1.0 mg with \nnor\nethindrone acetate); or high-dose estro -\ngen plus progestin (CEE 1.25 mg or estradiol \n2.0 m\ng combined with the same progestins).\nResults. Among 119 evaluable women with \nPOI (mean age, 30.3 years), the use of COC \nwas associated with the most positive BMD \ntrends. For women using COC or high-dose \nEPT , BMD at the lumbar spine increased. By \ncontrast, BMD of the lumbar spine declined \nThe author reports serving on the advisory boards of \nPfizer (contraception) and Mithra, and that the Uni-\nversity of Florida has received clinical trial support \nfrom Mithra. \ndoi: 10.12788/obgm.0048\n\nExamining the EVIDENCE\nin women who used no treatment or low-\ndose EPT .1\nOther studies’ take on dose, \nroute of administration, and cost \nconsiderations\nSequelae of POI include infertility, bother -\nsome hot flashes, vaginal dryness, sexual dys-\nfunction, mood disorders, and an elevated risk \nof c\nardiovascular disease, dementia, Parkin-\nson’s disease, and osteoporosis. Importantly, \nc\nlinicians and patients need to understand \nthat the results from the Women’s Health Ini-\ntiative studies do n ot apply to women with \nPOI.2 Physiologic doses of HT (that is, doses \nhigher than those used to treat menopausal \nsymptoms in women with normal/spontane-\nous menopause) are appropriate for women \nw\nith POI, at least until they reach the normal \nage of menopause (51 to 52 years).\nA clinical trial conducted in Scotland \nin women with POI found that high-dose \ntransdermal estrogen (application of one \nto two 0.1-mg estradiol patches) daily had \nan impact on BMD that was more positive \nthan that of an oral contraceptive formulated \nwith EE 30 µg.\n3 Likewise, a trial in the United \nStates found that, among oligo-amenorrheic \nathletes, a hormone replacement regimen \nusing a 0.1-mg estradiol patch had a more \npositive impact on BMD than an oral contra-\nceptive formulated with EE 30 µg.\n4\nAlthough Carvalho Gazarra and col -\nleagues acknowledged awareness of reports \ns\nuggesting the skeletal health benefits of \nhigh-dose estradiol patches, in the Brazilian \npublic health system oral hormone therapy \nis less expensive and oral contraceptives are \navailable at no charge.\n1 ●\nWHAT THIS EVIDENCE MEANS FOR PRACTICE\nWhen replacing estrogen and progestin in young women who \nlack ovarian function, it is appropriate to use considerably higher \ndoses than those used to treat bothersome vasomotor symptoms \nin women with normal/spontaneous menopause. From the per -\nspective of venous thromboembolism risk, the transdermal route \nof administration is safer than the oral route,\n5 and the Scottish \nand US studies discussed here indicate that transdermal estradiol \nis an effective approach to maintaining skeletal health in young \nwomen without ovarian function. Accordingly, hormonal manage-\nment with high-dose transdermal estradiol with a progestin (such \nas progesterone 200–300 mg at bedtime or medroxyprogesterone \n5–10 mg daily) represents an appropriate strategy. In situations \nwhere transdermal estradiol plus oral progestin treatment is not \ncovered by health insurance or acceptable to the patient, an oral \nestrogen-progestin contraceptive formulated with EE 30 or 35 µg \nwill provide protection against bone loss.\nReferences\n1. C arvalho Gazarra LB, Bonacordi CL, Yela DA, et al. Bone\nmass in women with premature ovarian insufficiency:\na comparative study between hormone therapy and\ncombined oral contraceptives. Menopause. 2020;27:  \n1110-1116.\n2.\n J\niang XD. Bone health and beyond in women with primary\novarian insufficiency: time to narrow the knowledge-action\ngap in care. Menopause. 2020;27:1101-1103.\n3.\n Cr\nofton PM, Evans N, Bath LE, et al. Physiological versus\nstandard sex steroid replacement in young women with\npremature ovarian failure: effects on bone mass acquisition \nand turnover. Clin Endocrinol (Oxf ). 2010;73:707-714.\n4.\n A\nckerman KE, Singhal V , Baskaran C, et al. Oestrogen\nreplacement improves bone mineral density in oligo-\namenorrhoeic athletes: a randomised clinical trial. Br J Sports\nMed. 2019;53:229-236.\n5.\n V\ninogradova Y, Coupland C, Hippisley-Cox J. Use of hormone\nreplacement therapy and risk of venous thromboembolism: \nnested case-control studies using the QResearch and CPRD\ndatabases. BMJ. 2019;364:k4810.","source_license":"CC0","license_restricted":false}