title: Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study.
abstract: Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.
authors.affiliation: National Institute on Aging, NIH, NIA-ASTRA Unit at Harbor Hospital, 3001 S. Hanover St., Baltimore, MD 21225, USA. ferruccilu@grc.nia.nih.gov
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggio
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lauretani
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Ceda
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ble
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.forename: Angela M
authors.initials: AM
authors.lastname: Abbatecola
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zuliani
authors.forename: Carmelinda
authors.initials: C
authors.lastname: Ruggiero
authors.forename: Giorgio
authors.initials: G
authors.lastname: Valenti
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000728:Androgens / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007558:Italy; D024821:Metabolic Syndrome / Q000503:physiopathology*; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
chemical_list: D000728:Androgens; D006728:Hormones; D012738:Sex Hormone-Binding Globulin; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone