The gonadotropic axis in hyperandrogenic adolescents.
Polycystic ovary syndrome (PCOS) is a common reproductive disorder that is first clinically diagnosable approximately 3 years after menarche. Women with PCOS have exaggerated gonadotropin secretion, with an elevated LH/FSH ratio, as well as an increased frequency and amplitude of LH pulsations. Since the elevated pulse frequency is a marker of unusually rapid hypothalamic GnRH secretion, these results imply a defect at the level of the hypothalamus. Such an abnormality could theoretically be a primary defect that could cause PCOS, and if so, would be expected to be detectable at the onset of puberty. How these abnormalities of hypothalamic and pituitary function relate to other, seemingly disparate, organ defects has not yet been delineated. We studied 99 PCOS patients and 42 normal controls with 8 to 12 hours of q10 min frequent blood sampling. Women with PCOS had significantly elevated mean LH levels, LH pulse amplitude, LH pulse frequency, and LH/FSH ratios compared to normal women. However, these abnormalities were not randomly distributed. All gonadotropin secretion parameters tended to be normal in PCOS patients when measured during the luteal phase or first 7 days after an ovulatory menses. There was a strong inverse relationship of mean LH, LH/FSH ratio, and LH pulse amplitude, but not frequency, with BMI. We hypothesize that this effect of body size occurs at the pituitary level. Several investigators have performed similar investigations in adolescent girls with regular and irregular menstrual cycles. Taken together, this evidence suggests that the gonadotropin defects appear as a very early finding in the development of PCOS, but the presence of abnormalities in both gonadotropin secretion and androgen secretion does not allow one to conclude that the gonadotropin defects are causal. We conclude that gonadotropin defects, particularly excess of serum LH, is a predominant finding in hyperandrogenic women, whether they are young peripubertal adolescents, or older perimenopausal women. Whether there is a primary neuroendocrine abnormality driving excess gonadotropin secretion that causes the hyperandrogenic condition, or whether the excess gonadotropin secretion reflects abnormal feedback of another factor, still remains unknown.
Taylor
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AE
Harvard Medical School, Reproductive Endocrine Unit, National Center for Infertility Research, Massachusetts General Hospital, Boston 02114, USA. aetaylor@partners.org
D000293:Adolescent; D000328:Adult; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006062:Gonadotropins / Q000502:physiology*; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D010060:Ovulation; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D011374:Progesterone / Q000097:blood; D012016:Reference Values; D014463:Ultrasonography
D006062:Gonadotropins; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone