Why High LH/FSH in Menopause Does Not Cause Ovulation
High LH and FSH levels in menopause fail to induce ovulation because the ovaries have depleted their follicular reserve and the remaining follicles are resistant to gonadotropin stimulation, making the elevated hormones a compensatory but futile response to ovarian failure. 1, 2
The Fundamental Mechanism of Ovarian Failure
The menopausal transition represents primary ovarian failure due to follicular depletion, not a problem with gonadotropin production 3. The pituitary gland responds appropriately by increasing FSH and LH secretion 10-15-fold in an attempt to stimulate any remaining ovarian follicles 4. However, this compensatory response cannot overcome the fundamental problem: there are insufficient functional follicles remaining to respond to the hormonal signals 1, 2.
Why the Follicles Cannot Respond
- The aging ovary experiences progressive depletion of primordial follicles, which begins years before menopause and accelerates during the perimenopausal transition 3
- The few remaining follicles become increasingly resistant to FSH stimulation, requiring higher hormone levels to achieve any response 3
- Even when follicles are present, they often lack the cellular machinery and granulosa cell function necessary to produce adequate estradiol or progress to ovulation 1
The Perimenopausal Evidence
Research during the menopausal transition reveals critical insights into this process:
- Women in perimenopause can exhibit postmenopausal FSH/LH levels yet still have high estrogen production and occasional ovulation, demonstrating that elevated gonadotropins alone do not guarantee ovarian failure 5
- Some perimenopausal women show FSH levels in the postmenopausal range followed by evidence of normal ovulation weeks later, proving the relationship is not simply dose-dependent 5, 4
- The pattern of rising FSH (which increases earlier than LH) reflects declining inhibin production from diminishing follicular reserves, not a failure of the pituitary response 4, 3
The Critical Distinction: Perimenopause vs. True Menopause
A crucial clinical pitfall is assuming that elevated FSH/LH always indicates permanent ovarian failure 4. During perimenopause:
- Postmenopausal FSH levels may occur with high estrogen levels, indicating follicular activity despite elevated gonadotropins 5
- Ovulatory cycles can occur within 16 weeks of the final menstrual period in women who later become truly postmenopausal 5
- FSH measurement has little diagnostic value during the transition because it fluctuates dramatically and cannot reliably predict future ovarian function 4
However, once true menopause is established (12 months of amenorrhea), the sustained elevation of FSH/LH with undetectable inhibin and low estradiol confirms irreversible follicular depletion 2, 4.
Additional Central Mechanisms in Aging
Beyond follicular depletion, there is evidence of hypothalamic-pituitary insensitivity to estrogen feedback in older reproductive-age women 6:
- Anovulatory cycles occur where estrogen peaks equivalent to those triggering LH surges in younger women fail to induce ovulation, indicating impaired positive feedback 6
- Some cycles show failure of estrogen to suppress LH through negative feedback 6
- This central component may contribute to the transition but is secondary to the primary ovarian failure 6
Clinical Implications
For diagnostic purposes in women under age 60, menopause diagnosis requires amenorrhea ≥12 months plus FSH and estradiol in postmenopausal ranges (elevated FSH with low estradiol) 2. For women age 60 or older, age and amenorrhea alone are sufficient 2.
The key distinction from conditions like functional hypothalamic amenorrhea (FHA) is critical: FHA shows low FSH/LH with low estrogen due to hypothalamic suppression, while menopause shows high FSH/LH with low estrogen due to ovarian failure 1, 7. In FHA, restoring pulsatile GnRH can induce ovulation because functional follicles remain 1, 7, whereas in menopause, no amount of gonadotropin stimulation can resurrect depleted follicular reserves.