title: Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women.
abstract: BACKGROUND
  Evidence is growing that the equilibrium between reactive oxygen species and antioxidants plays a vital role in women's reproductive health.
  
  
  OBJECTIVE
  The objective of this study was to evaluate variations in serum antioxidant concentrations across the menstrual cycle and associations between antioxidants and reproductive hormones and anovulation among healthy women.
  
  
  METHODS
  The BioCycle Study, a prospective cohort, followed 259 women aged 18-44 y for up to 2 menstrual cycles. Serum fat-soluble vitamin and micronutrient (α-tocopherol, γ-tocopherol, retinol, lutein, lycopene, and β-carotene), ascorbic acid, and reproductive hormone concentrations were measured 5-8 times/cycle. We used weighted linear mixed models to assess associations between antioxidants and hormone concentrations, after adjustment for age, race, body mass index, parity, sleep, pain medication use, total energy intake, concurrent hormones, serum cholesterol, F2-isoprostanes, and other antioxidants. Generalized linear models were used to identify associations with anovulation.
  
  
  RESULTS
  Serum antioxidant concentrations varied across the menstrual cycle. Retinol and α-tocopherol were associated with higher estradiol [RR: 1.00 pg/mL (95% CI: 0.67, 1.34 pg/mL); RR: 0.02 pg/mL (95% CI: 0.003, 0.03 pg/mL), respectively] and testosterone [RR: 0.61 ng/dL (95% CI: 0.44, 0.78 ng/dL); RR: 0.01 ng/dL (95% CI: 0.001, 0.01 ng/dL), respectively]. Ascorbic acid was associated with higher progesterone (RR: 0.15 ng/mL; 95% CI: 0.05, 0.25 ng/mL) and with lower follicle-stimulating hormone (RR: -0.06 mIU/mL; 95% CI: -0.09, -0.03 mIU/mL). The ratio of α- to γ-tocopherol was associated with an increased risk of anovulation (RR: 1.03; 95% CI: 1.01, 1.06).
  
  
  CONCLUSIONS
  These findings shed new light on the intricate associations between serum antioxidants and endogenous hormones in healthy premenopausal women and support the hypothesis that concentrations of serum vitamins affect steroidogenesis even after adjustment for oxidative stress.
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; mumfords@mail.nih.gov.
authors.forename: Sunni L
authors.identifier: http://orcid.org/0000-0003-0133-3176
authors.initials: SL
authors.lastname: Mumford
authors.affiliation: Departments of Biotechnical and Clinical Laboratory Sciences and.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Browne
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Karen C
authors.identifier: http://orcid.org/0000-0003-1771-3157
authors.initials: KC
authors.lastname: Schliep
authors.affiliation: Department of Epidemiology and Biostatistics, The George Washington University School of Public Health and Health Services, Washington, DC;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schmelzer
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; Program of Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; and.
authors.forename: Torie C
authors.initials: TC
authors.lastname: Plowden
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Kara A
authors.identifier: http://orcid.org/0000-0003-2431-2079
authors.initials: KA
authors.lastname: Michels
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Lindsey A
authors.identifier: http://orcid.org/0000-0003-0539-8110
authors.initials: LA
authors.lastname: Sjaarda
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; Program of Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; and.
authors.forename: Shvetha M
authors.identifier: http://orcid.org/0000-0003-2178-6623
authors.initials: SM
authors.lastname: Zarek
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Perkins
authors.affiliation: School of Community Health, Portland State University, Portland, OR.
authors.forename: Lynne C
authors.identifier: http://orcid.org/0000-0002-7332-6170
authors.initials: LC
authors.lastname: Messer
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Rose G
authors.initials: RG
authors.lastname: Radin
authors.affiliation: Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY;
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD;
authors.forename: Enrique F
authors.identifier: http://orcid.org/0000-0003-3757-641X
authors.initials: EF
authors.lastname: Schisterman
mesh_terms: D000293:Adolescent; D000328:Adult; D000858:Anovulation / Q000097:blood; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000097:blood; D002338:Carotenoids / Q000097:blood; D002149:Energy Intake; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D016014:Linear Models; D014975:Lutein / Q000097:blood; D000077276:Lycopene; D008597:Menstrual Cycle / Q000097:blood / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects* / Q000378:metabolism; D017697:Premenopause / Q000097:blood; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood; D014801:Vitamin A / Q000097:blood; D055815:Young Adult; D024502:alpha-Tocopherol / Q000097:blood; D019207:beta Carotene / Q000097:blood; D024504:gamma-Tocopherol / Q000097:blood
chemical_list: D000975:Antioxidants; D028441:F2-Isoprostanes; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D013739:Testosterone; D011374:Progesterone; D024504:gamma-Tocopherol; D005640:Follicle Stimulating Hormone; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D000077276:Lycopene; D014975:Lutein
keywords: antioxidants; estrogen; ovulation; progesterone; vitamins