Premature ovarian failure and dehydroepiandrosterone

26 11 2008

To the Editor:

We were very pleased to read the report by Mamas & Mamas (1), which reported success with  dehydroepiandrosterone (DHEA) treatment in women with premature ovarian senescence. Considering some of the questions such treatment has generated in the profession when we previously reported a series of controlled studies on DHEA supplementation (2-5), it is, however, of crucial importance that appropriate terminology be used when DHEA results are reported.

Premature ovarian failure (POF) is generally defined by premature FSH elevations above 40-50 mIU/ml under age 40 to 42 years (6). Only at most three patients in the reported series, therefore, qualified for such a diagnosis. The remaining women would qualify for what we have defined under the acronym premature ovarian aging (POA), which needs to be clearly discriminated from POF since such patients do not fulfill above-noted criteria for POF, though usually demonstrating elevated FSH levels (7). Because of significant pregnancy rates in POA women after DHEA supplementation, we now routinely treat women up to FSH levels of 40.0 mIU (2). Like Mamas & Mamas we also noted a surprising number of spontaneous pregnancy rates in women on DHEA supplementation, while waiting to be initiated into an IVF cycle (2).

Mamas and Mamas’s study is, however, unique in reporting such spontaneous pregnancies in women with POA, and these findings are very exciting because they suggest further potential applications for DHEA supplementation that deserve investigation. Their data also further validate the clinical utilization of DHEA in women with severely diminished ovarian reserve.

Since so far practically all clinical data on the utilization of DHEA in treatment of infertility, except for a preliminary initial report by Casson et al. (8.) have come from our center, we welcome the publication of additional experiences by other investigators. As we have twice failed in recruiting adequate patient numbers for prospectively randomized, placebo-controlled DHEA studies (once in New York City and once in collaboration with a number of European centers) because patients with severely diminished ovarian reserve simply do not feel they have time to be randomized to placebo, other controlled study formats may have to be utilized.

David H. Barad, MD MS
Andrea Weghofer, MD PhD
Norbert Gleicher, MD
The Center for Human Reproduction
New York, NY

References:
1. Mamas L, Mamas E 2008 Premature ovarian failure and dehydroepiandrosterone. Fertil Steril. 2008 Mar 3. [Epub ahead of print]

2. Barad D, Brill H, Gleicher N 2007 Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet 24:629-34.

3. Barad D, Gleicher N 2005 Increased Oocyte Production after Treatment with Dehydroepiandrosterone. Fertil Steril 84:756.

4. Barad D, Gleicher N 2006 Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 21:2845-49.

5. Brill H, Barad DH, Gleicher N 2006 O-289: Dehydroepiandrosterone (DHEA) supplementation and pregnancy outcome: Effect on pregnancy rate and speed of conception. Fertility and Sterility 86:S124-S125.

6. Pal L, Santoro N 2002 Premature ovarian failure (POF): discordance between somatic and reproductive aging. Ageing Res Rev 1:413-23.

7. Barad DH, Weghofer A, Gleicher N 2007 Age-specific levels for Basal follicle-stimulating hormone assessment of ovarian function. Obstet Gynecol 109:1404-10.

8. Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE 2000 Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 15:2129-32.

Published online in Fertility and Sterility  doi: 10.1016/j.fertnstert.2008.12.134

The Authors Respond:

We would like to thank Drs Barad, Weghofer and Gleicher of the Center for Human Reproduction for their letter referring to our  article. We find their comment on agreeing to an appropriate terminology to be used when DHEA results are reported, justifiable.  

They are probably right in stating that only three of the patients in our study qualify for what is defined as premature ovarain failure (POF). However, according to our reference, POF is defined as “early depletion of ovarian follicles before the age of 40…. These patients present with amenorrhea or oligomenorrhea and elevated FSH levels > 40IU/L” (1).  All of the patients of our study had secondary amenorrhea and received the same DHEA treatment. Even the one patient with FSH level of 30 IU/L (rightly defined as POA) had amenorrhea for 12 months, as much as the one with FSH level of 102 IU/L.

We must note here that the study on POF and DHEA is ongoing and our results continue to be promising. Seven more patients with POF have been referred to our Centre and received DHEA treatment, and all of them achieved pregnancy.

In all, we are most content to use a supplemental DHEA treatment for cases that otherwise would have required egg donation or other more invasive treatments. 

Leonidas Mamas MD
Eudoxia Mamas MBBS
Neogenesis IVF Centre
Athens, Greece

Reference
1. Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. Williams Textbook of Endocrinology, 10th edition. Philadelphia: Saunders 2003: 637-8.

Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2008.12.108

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