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The Early Dehydroepiandrosterone Sulfate Rise of Adrenarche and the Delay of Pubarche Indicate Primary Ovarian Failure in Turner Syndrome

University Children’s Hospital, D-72076 Tuebingen, Germany

Address all correspondence and requests for reprints to: Dr. Gerhard Binder, Section of Pediatric Endocrinology, University Children’s Hospital, Hoppe Seyler Strasse 1, D-72076 Tuebingen, Germany. E-mail: gerhard.binder{at}med.uni-tuebingen.de.

Pubarche without thelarche has been taken as clinical evidence that adrenarche is independent of gonadarche in females. This study examines whether the course of adrenarche [rise of serum dehydroepiandrosterone sulfate (DHEAS)] and pubarche (Tanner stage PH2) is independent from ovarian function. Serum DHEAS levels (n = 867) were longitudinally measured in 111 girls with Turner syndrome between 1990 and 2002. Of these, 22 had spontaneous puberty onset (Tanner stage B2), and 45 had primary ovarian failure (POF). Serum DHEAS levels were assayed by chemiluminescence and compared with those of healthy girls (n = 322; age range, 3–17 yr in both groups). Between the ages of 7 and 17 yr, girls with Turner syndrome had significantly higher age-related DHEAS levels than normal girls (P 0.02). Moreover, in the 9- to 15-yr-old girls, DHEAS levels were significantly higher in girls with Turner syndrome and POF than in Turner syndrome girls with spontaneous puberty onset (P 0.02). This discrepancy was caused by an earlier adrenarche (DHEAS levels reaching 1.1 µmol/liter) in Turner syndrome girls with POF, which occurred at a median age of 8.3 yr (80% confidence interval, 6.5–10.4 yr) vs. 10.5 yr (8.6–12.2) and 11.0 yr (8.9–12.6) in Turner syndrome girls with spontaneous puberty onset and normal girls, respectively (P = 0.003). In contrast, pubarche was delayed in Turner syndrome girls with POF [median age, 13.0 yr (80% confidence interval, 10.6–15.0) vs. 11.9 yr (10.5–13.2) in Turner syndrome girls with spontaneous puberty onset (P = 0.02) and 11.6 yr (10.6–12.5) in normal girls]. Primary gonadal failure in Turner syndrome is associated with an earlier onset of adrenarche, but delayed pubarche. These data demonstrate that normal timing of adrenarche is dependent on gonadal function and suggest that normal pubarche is the clinical manifestation of the ovarian conversion of DHEAS to active androgens.

This study was supported by the Growth Research Center Tübingen (Pharmacia, Pfizer).

Abbreviations: DHEA, Dehydroepiandrosterone; DHEAS, DHEA sulfate; POF, primary ovarian failure.