New PCOS-like phenotype in older infertile women of likely autoimmune adrenal etiology with high AMH but low androgens. Issue 167 (March 2017)

• Record Type: Journal Article
• Authors: Gleicher, Norbert; Kushnir, Vitaly A.; Darmon, Sarah K.; Wang, Qi; Zhang, Lin; Albertini, David F.; Barad, David H.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 167(2017)
• Page Start: 144
• Page End: 152
• Publication Date: 2017-03
• Subjects: ACTH adrenocorticotrophic hormone -- AI adrenal insufficiency -- AMH anti-Müllerian hormone -- AR androgen receptor -- C cortisol -- CP clinical pregnancies -- CRP C-reactive protein -- DHEA dehydroepiandrosterone -- DHEAS dehydroepiandrosteroen sulphate -- FSH follicle stimulating hormone -- FOR functional ovarian reserve -- GCs granulosa cells -- hMG human menopausal gonadotropin -- Ig immunoglobulin -- IL-6 interleukin 6 -- IVF in vitro fertilization -- LB live births -- PCOS polycystic ovary syndrome -- SHBG sex hormone binding globulin -- T testosterone -- TPO thyroid peroxidase; Polycystic ovary syndrome (PCOS) -- Adrenal insufficiency (AI) -- Anti-Müllerian hormone (AMH) -- Testosterone -- Functional ovarian reserve (FOR) -- In vitro fertilization (IVF); Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2016.12.004
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: We discovered a previously unknown hyo-androgenic polycystic ovary syndrome (PCOS) phenotype. Its hypo-androgenism appears adrenal in origin, representing insufficiency of the zona reticularis. Since closely associated with anti-thyroid autoimmunity, it, likely, is also autoimmune in etiology. This, therefore, suggests that, like the other two zonae, the zona-reticularis can also be affected by autoimmunity. Adrenal hypo-androgenism, therefore, has to be considered a potential component of autoimmune adrenal insufficiency. Abstract: How anti-Müllerian hormone (AMH) and testosterone (T) interrelate in infertile women is currently largely unknown. We, therefore, in a retrospective cohort study investigated how infertile women with high-AMH (AMH ≥75th quantile; n = 144) and with normal-AMH (25th–75th quantile; n = 313), stratified for low-T (total testosterone ≤19.0 ng/dL), normal-T (19.0–29.0 ng/dL) and high-T (>29.0 ng/dL) phenotypically behaved. Patient age, follicle stimulating hormone (FSH), dehyroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol (C), adrenocorticotrophic hormone (ACTH), IVF outcomes, as well as inflammatory and immune panels were then compared between groups, with AMH and T as variables. We identified a previously unknown infertile PCOS-like phenotype, characterized by high-AMH but, atypically, low-T, with predisposition toward autoimmunity. It presents with incompatible high-AMH and low-T (<19.0 ng/dL), is restricted to lean PCOS-like patients, presenting delayed for tertiary fertility services. Since also characterized by low DHEAS, low-T is likely of adrenal origina, and consequence of autoimmune adrenal insufficiency since also accompanied by low-C and evidence of autoimmunity. DHEA supplementation in such patients equalizes low- to normal-T and normalizes IVF cycle outcomes. Once recognized, this high-AMH/low-T phenotype is surprisingly common in tertiary fertility centers but, currently, goes unrecognized. Its likely adrenal autoimmune etiology offers interesting new directions for investigations of adrenals control over ovarian function via adrenal androgen production.