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Premature ovarian failure (POF) is a devastating condition for women of childbearing age with serious health consequences, including distress, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and increased mortality. In addition to the mainstay estrogen therapy, stem cell the. FOLFOX versus POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel plus FOLFOX) as a first-line treatment in advanced gastric cancer (AGC): A multicenter, randomized phase II trial, FNF-004 trial.

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A small, first prospectively randomized clinical trial of DHEA supplementation in women with premature ovarian failure (POF), now frequently called primary ovarian insufficiency (POI) , was reported in the January issue of the prestigious Journal of Clinical Endocrinology and Metabolism (JCEM) by Chinese colleagues from Hong Kong (Yeung Y et al., J Clin Endocronol Metab 2013;98:380-388).

The study randomized 22 true POF/POI patients (FSH around 100 mIU/mL and AMH at 0) to either DHEA or placebo group. After 12 and 20 weeks, the study revealed higher antral follicle counts and larger ovarian volume in DHEA-treated women but did not demonstrate improvements in either FSH or AMH values. DHEA-treated patients also demonstrated more follicles above 10mm in size.

The authors don’t mention pregnancies in their paper because it is unlikely that in any patient population with outright POF/POI pregnancies is frequent enough to surface in a small study of 22 patients. Indeed, here at CHR, we have treated significantly more women with POF/POI, and in over five years, we have seen only two (2) clinical pregnancies that went to term.

It should also not surprise that FSH and AMH did not improve because even in POA/OPOI patients it does not change in response to DHEA supplementation. AMH, however, does improve in some POA/OPOI patients and such an improvement is a good prognostic sign for pregnancy chances.

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It is important to emphasize that this study was not performed in women with premature ovarian aging (POA), often also called occult primary ovarian insufficiency (OPOI), but in women with outright POF/POI. CHR investigators, who have extensively published on DHEA use in POA/OPOI, have not been able to accumulate adequate patient numbers for a study on POF/POI so far. Only one small prior study has been published in the literature on DHEA use in POF/POI patients, published by a Greek group, which actually included POA/OPOI patients and, therefore, did not really reflect on POF/POI.

The study of Yeung and co-workers is, nevertheless, of importance, because it demonstrates in a prospectively randomized study that, even in women with POF/POI, generally considered the end stage of POA/OPOI, the ovaries still respond to DHEA supplementation. If ovaries do respond to DHEA supplementation at such a late stage of ovarian senescence, they, of course, can also be expected to respond, likely even more vigorously, at earlier stages of POA/OPOI.

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On a side note, the authors also confirmed low testosterone levels in POF/POI patients, and their rise after DHEA supplementation, recently reported by CHR investigators on POA/OPOI patients.

Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.

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