Sci. Aging Knowl. Environ., 26 March 2003
Mistimed fertility hormone in older women spurs premature ovulation
Key Words: corpus luteum pituitary endometrium
Like a symphony percussionist who drums too soon, a hormone that beats time for ovulation jumps in early during older women's fertility cycles, according to new work. In both cases, the timing error leads to discord. The observation suggests why women pushing 40 are less fertile than their more nubile sisters.
The cadence of the ovulatory cycle arises from a hormonal orchestra whose players fade in and out predictably. The theme repeats approximately every 30 days: Following menstruation, quantities of the hormone inhibin A drop, allowing follicle stimulating hormone (FSH) quantities to rise. FSH nurtures the egg and its follicular nursery maid until the follicle produces estrogen and inhibin A. Then inhibin A blocks FSH release while estrogen calls up luteinizing hormone (LH). LH liberates the mature egg from the follicle, and progesterone concentrations increase in anticipation of pregnancy. With no fertilization to maintain progesterone production, amounts of the hormone plunge, and the woman menstruates.
As women approach menopause, their hormones get out of whack (see "More Than a Hot Flash"). According to conventional wisdom, FSH in particular tends to lose its place; it is present after ovulation in women older than 35. But no one knows when FSH starts to surge, nor how long it lingers. The cause of decreased fertility in the perimenopausal years is controversial, but some researchers blame persistent FSH. The older women get, the faster they deplete their store of immature follicles. If this reserve normally soaks up FSH, loss of it could lead to excess FSH throughout the cycle, which might decrease fertility through some unknown mechanism (see "Menopause Mouse"). Alternatively, an early appearance of FSH might ripen eggs too soon, rendering them incompetent for fertilization.
To probe which hypothesis underlies women's fertility decline, gynecologist Piet van Zonneveld and colleagues at the University Medical Center Utrecht, Netherlands, measured hormone concentrations every 2 days in older and younger women and scanned their developing follicles with ultrasound. Unlike in younger women, in 40-somethings FSH quantities surged while progesterone quantities were still high, indicating that FSH doses don't remain high, as previously thought; instead, they return prematurely. This hasty entrance of FSH shortened the monthly cycles in older women by 2 to 3 days compared to those in the 20-somethings. The older women's follicles egged the eggs on to maturation too soon after menstruation, and the women ovulated earlier than normal. The researchers aren't sure how the drifting cycle translates into decreased fertility. Perhaps, says van Zonneveld, the earlier follicle growth creates circumstances that are "less optimal" for the egg, such as exposing it to progesterone, which might be harmful.
According to reproductive biologist Aaron Hsueh of Stanford University Medical Center, this study is the first to provide "solid data" supporting the proposition that FSH in older women is jumping the gun. If a conductor can retrain the drummer with bad timing, perhaps researchers can adjust the premature entry of hormones that create rhythmic chaos.
--Mary Beckman; suggested by Lynnette Gerhold
March 26, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150