title: New PCOS-like phenotype in older infertile women of likely autoimmune adrenal etiology with high AMH but low androgens.
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 ≤19.0ng/dL), normal-T (19.0-29.0ng/dL) and high-T (>29.0ng/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 (<19.0ng/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.
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States; The Foundation for Reproductive Medicine, New York, NY 10020, United States; Stem Cell Biology and Molecular Embryology Laboratory, Rockefeller University, New York, NY 10016, United States; Department of Obstetrics and Gynecology, Vienna University School of Medicine, 1090 Vienna, Austria. Electronic address: ngleicher@thechr.com.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gleicher
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States; Department of Obstetrics and Gynecology, Wake Forest University, Winston Salem, NC 27101, United States.
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Kushnir
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Darmon
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States; Stem Cell Biology and Molecular Embryology Laboratory, Rockefeller University, New York, NY 10016, United States.
authors.forename: David F
authors.initials: DF
authors.lastname: Albertini
authors.affiliation: The Center for Human Reproduction, New York, NY, 10021, United States; The Foundation for Reproductive Medicine, New York, NY 10020, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Barad
mesh_terms: D000311:Adrenal Glands / Q000196:embryology / Q000473:pathology*; D000309:Adrenal Insufficiency / Q000150:complications / Q000175:diagnosis; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D054304:Anti-Mullerian Hormone / Q000378:metabolism*; D015551:Autoimmunity / Q000276:immunology; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism*; D008875:Middle Aged; D010053:Ovary / Q000378:metabolism; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D013739:Testosterone / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D016896:Treatment Outcome; D015385:Zona Reticularis / Q000378:metabolism
chemical_list: D000728:Androgens; D013739:Testosterone; D054304:Anti-Mullerian Hormone
keywords: Adrenal insufficiency (AI); Anti-Müllerian hormone (AMH); Functional ovarian reserve (FOR); In vitro fertilization (IVF); Polycystic ovary syndrome (PCOS); Testosterone