Norbert Gleicher1,2,3,4, Vitaly A Kushnir5,6, Sarah K Darmon5, Qi Wang5, Lin Zhang5, David F Albertini5,7, David H Barad5,8. 1. The Center for Human Reproduction, New York, NY, 10021, USA. ngleicher@thechr.com. 2. The Foundation for Reproductive Medicine, New York, NY, 10020, USA. ngleicher@thechr.com. 3. Stem Cell Biology and Molecular Embryology Laboratory, Rockefeller University, New York, NY, 10016, USA. ngleicher@thechr.com. 4. Department of Obstetrics and Gynecology, Vienna University School of Medicine, 1090, Vienna, Austria. ngleicher@thechr.com. 5. The Center for Human Reproduction, New York, NY, 10021, USA. 6. Department of Obstetrics and Gynecology, Wake Forest University, Winston Salem, Winston Salem, NC, 27101, USA. 7. Stem Cell Biology and Molecular Embryology Laboratory, Rockefeller University, New York, NY, 10016, USA. 8. The Foundation for Reproductive Medicine, New York, NY, 10020, USA.
Abstract
BACKGROUND: A recent report described a new PCOS-like phenotype in lean older infertile women, and was characterized by high age-specific anti-Müllerian hormone (AMH) but hypo- rather than the expected hyper-androgenism. The hypo-androgenism was, furthermore, characterized of, likely, adrenal origin and autoimmune etiology. PATIENTS AND METHODS: We extracted data on 708 consecutive infertility patients, and separated them into three age-strata, <35, 36-42, and >42 years. In each stratum, we investigated how levels of anti-Müllerian hormone (AMH) and testosterone (T) interrelate between high-AMH (AMH ≥ 75th quantile) and normal AMH (25th-75th quantile) and low-T (total testosterone ≤19.0 ng/dL), normal-T (19.0-29.0 ng/dL) and high-T (>29.0 ng/dL). High-AMH cycles were presumed to reflect PCOS-like patients. Routine in vitro fertilization (IVF) cycle outcomes and clinical phenotypes of patients were then compared between groups with AMH and T as statistical variables. RESULTS: This hypo-androgenic PCOS-like phenotype already exists in age stratum <35 years. It appears to arise from a lean, at very young ages hyper-androgenic PCOS phenotype that develops in comparison to controls (likely autoimmune-induced) insufficiency of the adrenal zona reticularis (low-T and low-DHEAS) and zona fasciculata (low-C), and is characterized by frequent evidence of autoimmunity. A degree of adrenal insufficiency, thus, concomitantly appears to affect adrenal androgen and, to lesser degrees, glucocorticoid production (mineralocorticoids were not investigated). CONCLUSIONS: Here investigated new PCOS-like phenotype demonstrates features compatible with what under Rotterdam criteria has been referred to as PCOS phenotype-D. If confirmed, the observation that the ontogeny of this phenotype already at young ages is, likely, driven by adrenal autoimmunity, supports the position of the androgen excess and PCOS society that the etiology of phenotype-D differs from that of classical hyper-androgenic PCOS of mostly ovarian etiology.
BACKGROUND: A recent report described a new PCOS-like phenotype in lean older infertile women, and was characterized by high age-specific anti-Müllerian hormone (AMH) but hypo- rather than the expected hyper-androgenism. The hypo-androgenism was, furthermore, characterized of, likely, adrenal origin and autoimmune etiology. PATIENTS AND METHODS: We extracted data on 708 consecutive infertilitypatients, and separated them into three age-strata, <35, 36-42, and >42 years. In each stratum, we investigated how levels of anti-Müllerian hormone (AMH) and testosterone (T) interrelate between high-AMH (AMH ≥ 75th quantile) and normal AMH (25th-75th quantile) and low-T (total testosterone ≤19.0 ng/dL), normal-T (19.0-29.0 ng/dL) and high-T (>29.0 ng/dL). High-AMH cycles were presumed to reflect PCOS-like patients. Routine in vitro fertilization (IVF) cycle outcomes and clinical phenotypes of patients were then compared between groups with AMH and T as statistical variables. RESULTS: This hypo-androgenic PCOS-like phenotype already exists in age stratum <35 years. It appears to arise from a lean, at very young ages hyper-androgenic PCOS phenotype that develops in comparison to controls (likely autoimmune-induced) insufficiency of the adrenal zona reticularis (low-T and low-DHEAS) and zona fasciculata (low-C), and is characterized by frequent evidence of autoimmunity. A degree of adrenal insufficiency, thus, concomitantly appears to affect adrenal androgen and, to lesser degrees, glucocorticoid production (mineralocorticoids were not investigated). CONCLUSIONS: Here investigated new PCOS-like phenotype demonstrates features compatible with what under Rotterdam criteria has been referred to as PCOS phenotype-D. If confirmed, the observation that the ontogeny of this phenotype already at young ages is, likely, driven by adrenal autoimmunity, supports the position of the androgen excess and PCOS society that the etiology of phenotype-D differs from that of classical hyper-androgenic PCOS of mostly ovarian etiology.
Authors: Ricardo Azziz; Enrico Carmina; Didier Dewailly; Evanthia Diamanti-Kandarakis; Héctor F Escobar-Morreale; Walter Futterweit; Onno E Janssen; Richard S Legro; Robert J Norman; Ann E Taylor; Selma F Witchel Journal: Fertil Steril Date: 2008-10-23 Impact factor: 7.329
Authors: Stefan R Bornstein; Bruno Allolio; Wiebke Arlt; Andreas Barthel; Andrew Don-Wauchope; Gary D Hammer; Eystein S Husebye; Deborah P Merke; M Hassan Murad; Constantine A Stratakis; David J Torpy Journal: J Clin Endocrinol Metab Date: 2016-01-13 Impact factor: 5.958