Early Start of Follicular Growth and Limited Oocyte Pool Helps Explain Age Related Fertility
Menstrual Cycles

Richard J. Fehring
Reprint from Current Medical Research
Vol 15, No 1-2, Winter/Spring 2004
Washington, DC
Reproduced with Permission

Researchers from the Netherlands recently conducted a study to help explain age-related loss of fertility by comparing menstrual cycle parameters from a group of healthy "relatively" young women with cycle parameters from a group of older women.1 The researchers recruited 26 "relatively" older women (mean age 42; range 41-46) matched them with 35 healthy younger women (mean age 31; range 22-34) and measured their follicular development (by serial transvaginal ultrasound), endometrial growth, and hormonal patterns (i.e., blood levels of LH, FSH, estradiol, and Inhibin A and B). The younger women generated 33 cycles of data and the older women 24 cycles of data.

The researchers found that on average the cycle lengths of the older women were almost 3 days shorter than the younger women's (26.5 days versus 29.0 days) and the shorter cycles were due to the average shorter length of the follicular phase (12.4 days versus 16.2 days). There were no statistical differences between the lengths of the luteal phase between the two groups. Other parameters that reached statistical differences were the cycle day that the dominant follicle was first observed (on average day 7.7 for the older women and day 10.5 for the younger women), the diameter of the follicle just before ovulation was smaller for the older women (19.8 mm versus 21.5 mm), FSH levels for the older women were significantly higher during the late luteal and early follicular phase than the younger women, LH and Inhibin B levels were lower for the older women and the early antral (i.e., immature follicles) follicular count was significantly higher in the younger women (13.6 versus 4.9). Progesterone levels in the luteal phase, endometrial thickness, and the peak of estradiol did not significantly differ between the two groups. The researchers stated that in contrast to the theory that older women had accelerated follicular development, their data suggest that older women have an earlier start to follicular development that begins in the luteal phase of the previous cycle.

The authors concluded that in spite of a dramatically decreased number of immature follicles, they found that follicular development, hormonal events and endometrial growth are remarkably undisturbed in older women, until the age of 45-46 years. They speculated that an earlier start in follicle growth in a less favorable hormonal environment coupled with a diminished oocyte pool could lead to decreased follicle and oocyte quality and thus result in diminished fertility among older women.


The authors of this study were careful to describe the differences in the smoking habits between the two groups of women but not the post-hormonal contraception use. They only said that the women needed to be off oral contraception for at least 2 cycles. I would think that the hormonal events of the cycle would be affected more by the post-pill hormones than smoking -especially in light of the German study of post-pill cycles reviewed earlier in this issue of CMR.2 Readers should also be aware that the groups were selected by convenience and that the differences in cycle parameters could be due to other factors. (RJF)

1 Van Zonneveld, P., Scheffer, G.J., & Broekmans, F.J.M, et al. Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women. Human Reproduction. 2003;18:495-501. [Back]

2 Gnoth, C., Frank-Hermann, P., & Sclunoll, A., et al. Cycle characteristics after discontinuation of oral contraceptives. Gynecological Endocrinology. 2002;16:307-317. [Back]