title: Testosterone for Poor Ovarian Responders: Lessons From Ovarian Physiology.
abstract: Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect on reproductive outcome. The rationale for asking this question lies in the existing scientific evidence derived from basic research and animal studies regarding the action of androgens during folliculogenesis, showing that their main effect in follicular development is defined during the earlier developmental stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because the short administration and the high dose of testosterone is not in line with the ovarian actions of androgens and the presence of androgen receptors during follicular development.
authors.affiliation: 1 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.|2 Fertility Clinic, Skive Regional Hospital, Skive, Denmark, and Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Polyzos
authors.affiliation: 3 Women's Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Davis
authors.affiliation: 1 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Drakopoulos
authors.affiliation: 2 Fertility Clinic, Skive Regional Hospital, Skive, Denmark, and Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Humaidan
authors.affiliation: 4 Clinic of Gynaecological Endocrinology and Reproductive Medicine, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: De Geyter
authors.affiliation: 5 Assisted Reproduction Unit, University Hospital, Quirón Madrid, Madrid, Spain.
authors.forename: Antonio Gosálvez
authors.initials: AG
authors.lastname: Vega
authors.affiliation: 6 Department of Obstetrics, Gynecology and Reproduction, Hospital Universitari Dexeus, Barcelona, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Martinez
authors.affiliation: 7 Imperial College London, London, United Kingdom.|8 Department of Hygiene and Epidemeology, University of Ioannina Medical School, Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Evangelou
authors.affiliation: 1 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Arne
authors.initials: A
authors.lastname: van de Vijver
authors.affiliation: 1 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Smitz
authors.affiliation: 1 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Tournaye
authors.affiliation: 6 Department of Obstetrics, Gynecology and Reproduction, Hospital Universitari Dexeus, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Barri
mesh_terms: D000728:Androgens / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D010062:Ovulation Induction; D016032:Randomized Controlled Trials as Topic; D020554:Sperm Injections, Intracytoplasmic; D013739:Testosterone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D013739:Testosterone
keywords: infertility; poor ovarian response; poor responders; testosterone