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More on the conversion of DHEA to testosterone

Nature Reviews Endocrinology volume 11, page 521 (2015)Cite this article

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We appreciate the interest of Kunicki and colleagues in our Review (Genetics of androgen metabolism in women with infertility and hypoandrogenism. Nat. Rev. Endocrinol. 11, 429–441; 2015),1 and are pleased to respond to their comments (DHEA in women with hypoandrogenism—debate remains open. Nat. Rev. Endocrinol. doi:10.1038/nrendo.2015.107).2 We fully agree with our Polish colleagues that what actually constitutes abnormally low levels of androgens in women with infertility has not yet been fully defined. This lack of clarity, however, is not only a problem in assessing androgen levels but, also, in assessing levels of all fertility-related hormones, which in their normal ranges are age-dependent.3,4

Kunicki and colleagues2 also do not differentiate between age-specific and functional hypoandrogenism. At certain advanced ages, testosterone or dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) levels of 8.68 nmol/l and 40.74 nmol/l, respectively, might, indeed, be normal on an age-specific basis; yet functionally, they might represent hypoandrogenism. We know this on the basis of a number of observations. Firstly, women with infertility who have normal age-specific androgen levels often present with increased levels of sex hormone-binding globulin (SHBG). When these women are given androgen supplements, their SHBG levels normalize in parallel with improving testosterone levels. This pattern is often most profoundly visible in young women under the age of 35 years with a history of polycystic ovary syndrome at an earlier age, when ovaries, it seems, have 'become used' to especially high levels of androgens. Secondly, women with low functional ovarian reserve almost universally have lower testosterone levels than women with normal ovarian function.5 Thirdly, androgen supplementation statistically relates to pregnancy success.6

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References

  1. Shohat-Tal, A., Sen, A., Barad, D. H., Kushnir, V. & Gleicher, N. Genetics of androgen metabolism in women with infertility and hypoandrogenism. Nat. Rev. Endocrinol. 11, 429–441 (2015).

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Authors and Affiliations

  1. Center for Human Reproduction, 21 East 69th Street, New York, 10021, NY, USA

    Aya Shohat-Tal, David H. Barad, Vitaly A. Kushnir & Norbert Gleicher

  2. Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, 14642, NY, USA

    Aritro Sen

Authors
  1. Aya Shohat-Tal
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  2. Aritro Sen
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  3. David H. Barad
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  4. Vitaly A. Kushnir
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Correspondence to Aya Shohat-Tal.

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Competing interests

N.G. and D.H.B. are listed as co-inventors on four awarded US patents, which claim therapeutic benefits of DHEA and other androgens in women with low functional ovarian reserve (US 7,615,544: 'Method of improving cumulative embryo score and quantity of fertilized oocytes, increasing euploidy rate and of normalizing ovarian function using an androgen such as dehydroepiandrosterone'; US 8,067,400: 'Androgen treatment in females'; US 8,501,719: 'Androgen treatment in females'; and US 8,501,718: 'Androgen treatment in females'). N.G. and D.H.B. are also listed as co-inventors on two awarded US patents, which are not related to the subject of this Review (US 8,629,120: 'Method of treatment related to the FMR1 gene'; and US 8,951,724: 'Detection of infertility risk and premature ovarian aging, addressing various claimed effects and diagnostic functions of the FMR1 gene on ovaries and female fertility'). N.G. owns shares in Fertility Nutraceuticals, a company that sells DHEA products, and both N.G. and D.H.B. receive patent royalties from this company. N.G. is also the owner of The Centre for Human Reproduction, New York, NY, USA. A.S.-T., A.S. and V.A.K. declare no competing interests.

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Shohat-Tal, A., Sen, A., Barad, D. et al. More on the conversion of DHEA to testosterone. Nat Rev Endocrinol 11, 521 (2015). https://doi.org/10.1038/nrendo.2015.108

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