All about follicle-stimulating hormone (FSH)

What is follicle-stimulating hormone?
Follicle-stimulating hormone (FSH) is a hormone produced in the pituitary gland in both females and males. It helps regulate development, growth, pubertal maturation, and reproductive processes (1).

What are the roles of follicle-stimulating hormone?
FSH plays important roles in both females and males (2):

• In females, FSH stimulates ovarian follicular growth and production of estrogen and initiates the release of an egg at ovulation.
• In males, FSH signals for the Sertoli cells of the testes to produce sperm (spermatogenesis).

What controls follicle-stimulating hormone levels in females?
Gonadotrophin-releasing hormone (GnRH) released from the hypothalamus (region of the brain) stimulates the synthesis and release of FSH from the pituitary along with another important hormone called luteinizing hormone (LH). FSH and LH travel through the blood to act on the ovaries (3).

The FSH stimulation of ovarian growth results in increased estrogen levels, which is detected by the hypothalamus and results in less GnRH release; hence less stimulation of FSH synthesis. However, when levels of estrogen reach a “tipping point”, it stimulates a surge in FSH and LH, which is what causes the release of an egg (ovulation). After ovulation, the ruptured follicle forms a corpus luteum that produces progesterone, which inhibits the release of any more FSH. During a normal menstrual cycle, this corpus luteum then breaks down, progesterone levels decrease again, and FSH starts to slowly increase once again (3).

How is follicle-stimulating hormone controlled in males?
In males, a similar negative feedback system occurs. FSH stimulates the production of testosterone in the testes, which is then detected by the hypothalamus. As testosterone levels increase, less GnRH is released and consequently, less FSH is synthesized and released. As testosterone levels fall, more GnRH is released to stimulate FSH synthesis to then act on the testes to initiate testosterone production (3).

What happens in females with low estrogen?
Low estrogen in females, can occur in primary ovarian failure, which is common in females with Turner syndrome. This low estrogen means there is no feedback loop to control FSH levels, and FSH can be significantly elevated (3).

There is of course also a perfectly natural estrogen decline in females too. As females age, their quantity and quality of eggs decrease. This means that the normal FSH stimulation of the ovaries doesn’t result in the same increases in estrogen that were occurring at a younger age. This is why FSH levels naturally rise around the menopausal period and remain higher during postmenopause (3).

Are FSH levels linked to male infertility?
Yes, FSH is required for proper sperm production. If FSH levels are too low, normal puberty and sperm production does not occur. In addition, elevated FSH levels are also a sign of infertility, as raised FSH is a sign of testicular failure, as there is not enough testosterone for the normal feedback control of FSH levels. This condition occurs in conditions such as Klinefelter’s syndrome in males (3).

How do FSH levels predict ovarian reserve?
Ovarian reserve refers to the quality and quantity of a woman’s eggs. Different tests are available to predict a women’s ovarian reserve, one of which is the day 3 FSH test. FSH levels fluctuate throughout the menstrual cycle with levels gradually increasing in the first half of the cycle until reaching a peak at ovulation before decreasing again. This is why measuring the basal FSH levels at day 3 (the third day of your period) is important to gain the most benefit from an FSH ovarian reserve test.

An FSH level of <10 mIU/mL at day 3 is considered normal for ovarian reserve testing. Higher basal FSH levels are indicative of a reduced ovarian response and lower ovarian reserve. However, a single elevated FSH reading may not be sufficient, so it is often recommended to also measure day 3 FSH levels in one or more subsequent cycles too (4).

References
1. Ulloa-Aguirre A, Reiter E, & Crépieux P. (2018). FSH Receptor Signaling: Complexity of Interactions and Signal Diversity. Endocrinol, 159 (8), 3020-3035.
2. Knudtson J. (2019) Female Reproductive Endocrinology. Merck Manual Professional Version.
3. Follicle-stimulating hormone. You and your hormones, an education resource from the Society for Endocrinology. (Reviewed Feb 2018).
4. Roudebush WE, Kivens WJ, Mattke JM. (2008) Biomarkers of Ovarian Reserve. Biomark Insights. 3, 259-268.