title: Fertility and ovarian function in high-dose estrogen-treated tall women.
abstract: OBJECTIVE
  High-dose estrogen treatment to reduce final height of tall girls has been shown to interfere with fertility. Ovarian function has not been studied. We therefore evaluated fertility and ovarian function in tall women who did or did not receive such treatment in adolescence.
  
  
  METHODS
  This was a retrospective cohort study of 413 tall women aged 23-48 yr, of whom 239 women had been treated. A separate group of 126 fertile, normoovulatory volunteers aged 22-47 yr served as controls.
  
  
  RESULTS
  Fertility was assessed in 285 tall women (157 treated, 128 untreated) who had attempted to conceive. After adjustment for age, treated women were at increased risk of experiencing subfertility [odds ratio (OR) 2.29, 95% confidence interval (CI) 1.38-3.81] and receiving infertility treatments (OR 3.44, 95% CI 1.76-6.73). Moreover, fecundity was notably affected because treated women had significantly reduced odds of achieving at least one live birth (OR 0.26, 95% CI 0.13-0.52). Remarkably, duration of treatment was correlated with time to pregnancy (r = 0.23, P = 0.008). Ovarian function was assessed in 174 tall women (119 treated, 55 untreated). Thirty-nine women (23%) exhibited a hypergonadotropic profile. After adjusting for age category, treated women had significantly higher odds of being diagnosed with imminent ovarian failure (OR 2.83, 95% CI 1.04-7.68). Serum FSH levels in these women were significantly increased, whereas antral follicle counts and serum anti-Müllerian hormone levels were decreased.
  
  
  CONCLUSIONS
  High-dose estrogen-treated tall women are at risk of subfertility in later life. Their fecundity is significantly reduced. Treated women exhibit signs of accelerated ovarian aging with concomitant follicle pool depletion, which may be the basis of the observed subfertility.
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Erasmus Medical Center-Sophia, 3015 GJ Rotterdam, The Netherlands. a.e.j.hendriks@erasmusmc.nl
authors.forename: A E J
authors.initials: AE
authors.lastname: Hendriks
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
authors.forename: O
authors.initials: O
authors.lastname: Valkenburg
authors.forename: S Lie
authors.initials: SL
authors.lastname: Fong
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: M A J
authors.initials: MA
authors.lastname: de Ridder
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
authors.forename: J A
authors.initials: JA
authors.lastname: Visser
authors.forename: A M
authors.initials: AM
authors.lastname: van Ginneken
authors.forename: A M
authors.initials: AM
authors.lastname: Boot
authors.forename: S L S
authors.initials: SL
authors.lastname: Drop
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000502:physiology; D006130:Growth Disorders / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced / Q000503:physiopathology; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D004967:Estrogens