title: Compensatory Increase in Ovarian Aromatase in Older Regularly Cycling Women.
abstract: BACKGROUND
  Serum estradiol (E2) levels are preserved in older reproductive-aged women with regular menstrual cycles despite declining ovarian function.
  
  
  OBJECTIVE
  The objective of the study was to determine whether increased granulosa cell aromatase expression and activity account for preservation of E2 levels in older, regularly cycling women.
  
  
  METHODS
  The protocol included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle.
  
  
  METHODS
  Healthy, regularly cycling older (36-45 y; n = 13) and younger (22-34 y; n = 14) women participated in the study.
  
  
  METHODS
  Hormone levels were measured in peripheral blood and follicular fluid aspirates and granulosa cell CYP19A1 (aromatase) and FSH-R mRNA expression were determined.
  
  
  RESULTS
  Older women had higher FSH levels than younger women during the early follicular phase with similar E2 but lower inhibin B and antimullerian hormone levels. Late follicular phase serum E2 did not differ between the two groups. Follicular fluid E2 [older (O) = 960.0 [interquartile range (IQR) 765.0-1419.0]; younger (Y) = 994.5 [647.3-1426.5] ng/mL, P = 1.0], estrone (O = 39.6 [29.5-54.1]; Y = 28.8 [22.5-42.1] ng/mL, P = 0.3), and the E2 to testosterone (T) ratio (O = 109.0 ± 41.9; Y = 83.0 ± 18.6, P = .50) were preserved in older women. Granulosa cell CYP19A1 expression was increased 3-fold in older compared with younger women (P < .001), with no difference in FSH-R expression.
  
  
  CONCLUSIONS
  Ovarian aromatase expression increases with age in regularly cycling women. Thus, up-regulation of aromatase activity appears to compensate for the known age-related decrease in granulosa cell number in the dominant follicle to maintain ovarian estrogen production in older premenopausal women.
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: N D
authors.initials: ND
authors.lastname: Shaw
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: S S
authors.initials: SS
authors.lastname: Srouji
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: C K
authors.initials: CK
authors.lastname: Welt
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: K H
authors.initials: KH
authors.lastname: Cox
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: J H
authors.initials: JH
authors.lastname: Fox
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: J A
authors.initials: JA
authors.lastname: Adams
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: P M
authors.initials: PM
authors.lastname: Sluss
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.A.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: J E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015571:Follicular Fluid / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007265:Inhibins; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D011962:Receptors, FSH / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D011962:Receptors, FSH; C422364:inhibin B; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase