Menopause: not just ovarian failure

Menopause is not simply the result of ovarian failure or depletion; evidently it's also the result of a hypothalamic-pituitary insensitivity to estrogen during the perimenopausal period, according to a multiethnic, observational, cohort study.

To reach that conclusion, researchers reviewed the daily urinary hormone levels of estrogen and progesterone metabolites, LH, and FSH of 160 women without luteal activity, categorizing them into three groups: those with estrogen increases with an LH surge, those with estrogen increases without an LH surge, and those with neither.

Women with low estrogen levels and an LH surge experienced more hot flashes than women in either of the other two groups. The authors reported that older reproductive-aged women frequently have anovulatory cycles with estrogen peaks that are equivalent to those resulting in LH surges in younger women, but no LH surges occur, indicating a lack of estrogen-positive feedback on the hypothalamus, which would normally stimulate the pituitary to secrete LH. In other anovulatory cycles, follicular-phase estrogen levels failed to lower LH secretion as occurs in younger women, indicating decreased estrogen-negative feedback on LH secretion.

Weiss G, Skurnick JH, Goldsmith LT, et al. Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA. 2004;292:2991-2996.