title: The investigation and management of severe hyperandrogenism pre- and postmenopause: non-tumor disease is strongly associated with metabolic syndrome and typically responds to insulin-sensitization with metformin.
abstract: BACKGROUND
  An androgen-secreting tumor needs to be excluded in any woman with severe hyperandrogenism. We sought to characterize patients with biochemical hyperandrogenism in respect of tumor versus non-tumor etiologies, explore possible links between non-tumor hyperandrogenism and metabolic syndrome, and ascertain whether metformin therapy can elicit diagnostic reductions in serum testosterone (T).
  
  
  METHODS
  Seven-year retrospective study of all women referred to a university hospital endocrinology service with baseline T >4.0 nmol/l. Dataset comprised age, menopausal status, body mass index (BMI), presence/absence of hypertension, diabetes, acanthosis or dyslipidemia, along with changes in BMI and serum T following intervention with metformin, oophorectomy or dexamethasone. Non-tumor hyperandrogenism was defined by normalization of serum T or >40% reduction from baseline.
  
  
  RESULTS
  Four out of 18 cases had adrenal carcinoma that was clinically obvious at initial presentation (one virilized, three Cushingoid). The remaining 14 were characterized by metabolic syndrome (BMI: 39.9 +/- 8.1 kg/m(2)), serum T of 6.14 +/- 1.6 nmol/l, and nadir serum T following intervention of 2.2 +/- 1.04 nmol/l. Diagnostic reductions in serum T occurred in 11/12 patients treated with metformin.
  
  
  CONCLUSIONS
  Non-tumor hyperandrogenism with markedly elevated serum T and associated metabolic syndrome is a defined clinical entity in postmenopause as well as in premenopausal women with polycystic ovary syndrome. This has hitherto been only sparsely documented in the published literature. A fall in serum T level in response to insulin-sensitizing therapy with metformin and lifestyle change may be a reassuring indicator that such women are highly unlikely to harbor an androgen-secreting tumor.
authors.affiliation: Department of Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
authors.forename: Suresh
authors.initials: S
authors.lastname: Vaikkakara
authors.forename: Ebaa
authors.initials: E
authors.lastname: Al-Ozairi
authors.forename: Eelin
authors.initials: E
authors.lastname: Lim
authors.forename: Andrew
authors.initials: A
authors.lastname: Advani
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.forename: R Andrew
authors.initials: RA
authors.lastname: James
authors.forename: Richard
authors.initials: R
authors.lastname: Quinton
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy*; D017698:Postmenopause / Q000502:physiology; D012189:Retrospective Studies; D013739:Testosterone / Q000097:blood / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D013739:Testosterone; D008687:Metformin