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Genetics of androgen metabolism in women with infertility and hypoandrogenism (May 2015)

nature
Title:
Genetics of androgen metabolism in women with infertility and hypoandrogenism
Journal:
Nature Reviews Endocrinology (2015)
Author(s):
Shohat-Tal A1, Sen A2, Barad DH1, Kushnir V1, Gleicher N1.
Author(s) affiliation:
1Center for Human Reproduction, 21 E. 69th Street, New York, NY 10021, USA.
2Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
 

 

 

 

Abstract taken from PubMed

Abstract:
Hypoandrogenism in women with low functional ovarian reserve (LFOR, defined as an abnormally low number of small growing follicles) adversely affects fertility. The androgen precursor dehydroepiandrosterone (DHEA) is increasingly used to supplement treatment protocols in women with LFOR undergoing in vitro fertilization. Due to differences in androgen metabolism, however, responses to DHEA supplementation vary between patients. In addition to overall declines in steroidogenic capacity with advancing age, genetic factors, which result in altered expression or enzymatic function of key steroidogenic proteins or their upstream regulators, might further exacerbate variations in the conversion of DHEA to testosterone. In this Review, we discuss in vitro studies and animal models of polymorphisms and gene mutations that affect the conversion of DHEA to testosterone and attempt to elucidate how these variations affect female hormone profiles. We also discuss treatment options that modulate levels of testosterone by targeting the expression of steroidogenic genes. Common variants in genes encoding DHEA sulphotransferase, aromatase, steroid 5α-reductase, androgen receptor, sex-hormone binding globulin, fragile X mental retardation protein and breast cancer type 1 susceptibility protein have been implicated in androgen metabolism and, therefore, can affect levels of androgens in women. Short of screening for all potential genetic variants, hormonal assessments of patients with low testosterone levels after DHEA supplementation facilitate identification of underlying genetic defects. The genetic predisposition of patients can then be used to design individualized fertility treatments.
Link to the paper on PubMed
 




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