Why does Follicle-Stimulating Hormone (FSH) increase during menopause?

From the Guidelines

FSH increases during menopause due to the depletion of ovarian follicles and declining estrogen production, leading to a compensatory increase in FSH secretion by the pituitary gland. As women approach menopause, their ovaries contain fewer follicles capable of responding to FSH stimulation. The reduced number of follicles leads to decreased estrogen production, which normally suppresses FSH through negative feedback on the pituitary gland. Without this inhibitory effect, the pituitary gland increases FSH secretion in an attempt to stimulate the remaining follicles to produce estrogen.

Some key points to consider include:

• The median age of menopause in women in the United States is 51 years, but ovarian production of estrogen and progestin begins to decrease years before the complete cessation of menses 1.
• FSH levels typically begin rising during perimenopause (the transition period before menopause) and can increase up to 10-20 times normal premenopausal levels.
• These elevated FSH levels, particularly when consistently above 30 mIU/mL, are often used as a diagnostic marker for menopause, though they should be interpreted alongside clinical symptoms like irregular periods and vasomotor symptoms.
• The use of hormone replacement therapy (HRT) for the management of menopausal symptoms should be made on the basis of discussions between a woman and her clinician, taking into account the potential risks and benefits 1.

In terms of the underlying physiology, the decrease in estrogen production leads to a decrease in the negative feedback on the pituitary gland, resulting in an increase in FSH secretion. This increase in FSH secretion is a natural response to the declining estrogen levels and is not necessarily a cause for concern. However, it can be used as a diagnostic marker for menopause, and clinicians should be aware of the potential risks and benefits of HRT in managing menopausal symptoms.

From the FDA Drug Label

Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.

The increase in FSH in menopause occurs because the negative feedback mechanism is disrupted due to the decrease in estrogen levels. As estrogen levels decline, the pituitary gland secretes more FSH and LH in an attempt to stimulate the ovaries to produce more estrogen. 2

From the Research

FSH Increase in Menopause

• The increase in Follicle-Stimulating Hormone (FSH) levels during menopause is a result of declining levels of inhibin B (INH-B), a dimeric protein that reflects the fall in ovarian follicle numbers 3, 4.
• As women approach menopause, the number of follicles in the ovaries decreases, leading to a decrease in inhibin B production, which in turn causes an increase in FSH levels 3.
• The rise in FSH is an established indirect marker of follicular activity, and its concentration begins to increase several years before clinical indications of approaching menopause 3.
• The variability of hormone levels during the menopausal transition makes FSH and estradiol unreliable markers of menopausal status 3, 4.
• FSH has been found to have non-unitary functions, including regulating bone mass, adipose tissue function, energy metabolism, and cholesterol production, which may be relevant to the pathogenesis of bone loss and metabolic disorders accompanying menopause 5.

Hormonal Changes in Menopause

• Menopause is characterized by a profound decline in follicle numbers, leading to a chronic hypo-estrogenic state, which causes menopausal symptoms and has long-term effects on bone and cardiovascular health 6.
• Estradiol levels remain relatively unchanged or tend to rise with age until the onset of the transition, and are usually well preserved until the late perimenopause, presumably in response to elevated FSH levels 3.
• Testosterone levels have been reported to fall by about 50% during reproductive life, but change little during the transition and may even rise after menopause 3.
• Dehydroepiandrosterone (DHEA) and DHEAS decline with age, without any specific influence of the menopause 3.