Conflict statement

We want to point out to readers of this article that The Center for Human Reproduction (CHR) holds a number of patents, which claim therapeutic benefits from androgen/DHEA supplementation of selected infertile women. CHR and some CHR employees, including this author, receive royalty payments from two companies, which have licensed these patents and, therefore, are entitled to use these claims in their marketing efforts. Moreover, Dr. Gleicher is a shareholder in one of these companies, Fertility Nutraceuticals, LLC.

Background

DHEA is the most abundant steroid hormone in our bodies, and is the precursor hormone for all sex hormones. It, in itself, has very low affinity to the androgen receptor (AR) (and mild affinity to the estrogen receptor) and, therefore, is functionally almost inert as an androgen. Moreover, DHEA within minutes from ingestion is metabolized to DHEAS. Both, DHEA and DHEAS, as storage forms, usually are to a degree in balance in the circulation, constantly changing back and forth. Increasing evidence suggests that this allows different organs to take up sufficient DHEA to produce organ-specific testosterone (T)-levels. It appears that, aside from ovaries and adrenals, other organs, for example, liver, endometrium, etc. also have the apparatus to produce T from DHEA. The overwhelming amount of T in the woman comes, however, almost evenly, from ovaries and adrenals.

The apparatus for adding a sulfate group to DHEA to produce DHEAS, however, exists almost exclusively only in the zona reticularis of the adrenals. This is diagnostically important, and is also important when patient under DHEA supplementation are clinically monitored: Since DHEA and DHEAS should be in reasonable balance, DHEA supplementation should result in quick increases in DHEA as well as DHEAS.

If only DHEA rises, the patient likely suffers from deficiency of sulfotransferase enzymes (SULT1A1 and SULT1E1) in the zona reticularis, and DHEA supplementation will, likely, not lead to adequate increases in T. Such patients then need to be directly supplemented with T.

It is also important to note that the zona reticularis shrinks with advancing age and, therefore, DHEAS levels decline as women (and men) are getting older.