FSH Abnormalities and Male Infertility
Low FSH Levels and Male Infertility
FSH is the hormonal signal that the pituitary gland uses to tell the spermatogenic cells within the testicles to make sperm. As discussed previously, a normal FSH (1.0–7.6 mIU/mL) is usually consistent with good sperm production, whereas an elevated FSH generally signals a possible testicular problem with sperm production (as the pituitary gland is trying to tell the testicles to make more sperm). However, if the FSH is low (<1.0 mIU/mL), then the testicles may not receive the necessary signal from the pituitary gland, and decreased sperm production can result even if the testicular sperm production “machinery” is normal.
Causes of Low FSH
Possible reasons for low FSH include:
1) Excess androgens. Elevated androgens can provide negative feedback to the pituitary gland, resulting in decreased FSH secretion by the gland. Exogenous testosterone is the most common cause of low FSH levels seen clinically (see “Exogenous Androgens” in Chapter 6 for more details). Other, much rarer causes include androgen-secreting tumors of the adrenal gland or testicles (see “Management of Elevated Testosterone Levels,” section) or congenital adrenal hyperplasia (see below).
2) Destruction of pituitary cells. Any process that damages the pituitary gland can impair its ability to produce FSH. One cause of pituitary damage is a tumor. Tumors can arise from the pituitary gland itself or from a structure adjacent to the pituitary gland, and both can destroy normal pituitary cells through tissue compression. The most common pituitary tumor is called a prolactinoma, which is generally benign but can suppress gonadotropin secretion both through elevated prolactin levels as well as local destruction of tissue. Other symptoms that may be associated with tumors in this area include headache, changes in vision, and deficiencies of thyroid or adrenal hormones. Other causes of pituitary damage include brain surgery, head radiation, trauma, stroke, and infiltrative or granulomatous disease.
3) Congenital/genetic problems. There are some rare but well-described genetic abnormalities that can result in problems with pituitary production of FSH. An example of this is Kallman’s Syndrome, which can present with a spectrum of medical findings including anosmia (inability to smell), midline structural defects (such as cleft palate), and significantly decreased pituitary function. For more information on Kallman's Syndrome, see the "Genetics and Male Infertility" section of this website.
4) Elevated prolactin. Prolactin levels can exert a negative influence on GnRH release by the hypothalamus, thereby decreasing FSH production from the pituitary gland. See the “Elevated Prolactin” section of this website for more information.
5) Drugs or medications. These can include chronic narcotic use, estrogens or progestins, excessive alcohol intake, or marijuana.
6) Congenital adrenal hyperplasia (CAH). Excess production of androgens by the adrenal glands can suppress FSH production and decrease sperm counts and quality. In men with CAH, testosterone levels are generally elevated and LH levels are low. In a man with high testosterone, low FSH and LH, and low sperm counts, then elevated levels of 17-OHP, ACTH, and androstenedione can be indicative of CAH. See the “Medical Conditions and Male Fertility” section of this website for more information on CAH.
7) Idiopathic low FSH. “Idiopathic” means that no discernible reason can be found to explain a clinical problem, such as low FSH production. Presumably the cells in the pituitary that make FSH either did not develop normally or stopped functioning, although the reason is unknown.
Evaluation of Low FSH Levels
A thorough history should be performed to look for any of the above risk factors. If a good reason for FSH suppression is not found (such as exogenous androgen use), then prolactin levels should be tested and a pituitary MRI should be done to make sure there are no structural abnormalities or masses on the pituitary. Other pituitary hormones—LH, TSH, ACTH—should also be assessed to see if the entire pituitary gland is being impacted, or just the cells that secrete FSH. If other pituitary function abnormalities are discovered, consult an endocrinologist. Elevated androgen levels may indicate the presence of congenital adrenal hyperplasia or possibly an androgen-secreting tumor.
Management of Low FSH
Addressing Reversible Causes of FSH Suppression
1) Discontinue use of all exogenous androgens: testosterone replacement, anabolic steroids, prohormones, T boosters. See the“Exogenous Androgens/Anabolic Steroids” section of this website for more information.
2) Stop any medications containing estrogens or progestins.
3) If you are taking narcotics for chronic pain, look into alternatives. Consult a pain management specialist to see if you can decrease the
dose of prescription narcotics or eliminate them altogether.
4) Limit alcohol to no more than four drinks per week, as this may affect FSH levels
5) Stop all illicit drug use, with professional help if necessary
6) It is generally recommended that any pituitary tumors that are discovered by imaging should be evaluated by a neurosurgeon, even
though many benign prolactinomas can be treated with medicine only and do not require surgery. If no tumor is found, elevated
prolactin levels often respond well to medical therapy (see the “Elevated Prolactin" section for more information on managing
hyperprolactinemia).
Stimulation of Endogenous FSH Production
FSH levels can be increased one of two ways: give exogenous FSH or stimulate the man’s own pituitary gland to make more FSH. When reversible causes of decreased FSH production are found and addressed (such as treating an elevated prolactin level or stopping exogenous androgens), the pituitary gland will often start making FSH again on its own. However, if no reversible causes are found, or if the FSH stays low despite discontinuation of reversible factors, then selective estrogen receptor modulators (SERMs) or, less commonly, anastrazole can be used to stimulate the pituitary gland to increase FSH production.
SERMs act upon the estrogen receptors in the pituitary gland to stimulate increased FSH (and LH) production. Anastrazole also has the ability to increase FSH levels indirectly by decreasing estradiol levels (and therefore decreasing the negative feedback that estradiol levels normally have on FSH secretion). See the "Low Testosterone" section of this website for more detailed information on the use of these medication.
Implanted GnRH pumps are available which can stimulate the pituitary to make more FSH, but these pumps are very expensive and not widely used.
An example would be a man who recently stopped taking anabolic steroids after using them for four years. He is started on HCG injections, and two weeks later his testosterone and estradiol levels are normal but his FSH is still low at 0.1. With time, this man’s FSH may rise on its own with just the HCG injections, as he gets further out from stopping his steroid use, but another option would be to add low-dose SERMs to raise his FSH levels; this may make the sperm return faster.
It’s important to note that treatments to stimulate increased endogenous FSH production rely upon an intact pituitary gland. If the pituitary gland has been significantly compromised because of, for example, trauma, surgery, radiation, or congenital developmental abnormalities, then these treatments are less likely to be effective.
Exogenous FSH Replacement
In patients who do not have an intact pituitary gland—for example, those with Kallman’s syndrome or radiation damage—or who have failed to respond to clomiphene therapy, then exogenous FSH is often an effective, albeit expensive, treatment. See the "FSH" section of this website for more information on exogenous FSH replacement therapy.
After FSH treatment is begun, sperm production restarts in an average of six to nine months; some men respond faster, within three months, while a few others need as much as a few years. Once a pregnancy has been achieved, the FSH injections can be stopped, as there are no other known health benefits of FSH besides fertility.
Elevated FSH Levels and male infertility
As described above, normal FSH levels range between 1.0 and 7.6 mIU/mL. When the brain senses that the testicles are making less sperm than normal, it releases more FSH into the bloodstream to get the testicles to make more sperm. An elevated FSH therefore suggests that the sperm-producing capacity of the testicles is decreased. Elevated FSH is not bad for fertility in and of itself; rather, it is a sign that the brain is responding properly to the low sperm production. There are no medications that can directly lower FSH. The only way to decrease FSH is to improve sperm production (through treatments such as correction of a varicocele, treatment of hypogonadism, etc.).
Normal FSH Levels Despite Decreased Sperm Production
In some circumstances, men with low sperm production are found to have FSH levels in the normal range (1.0–7.6 mIU/mL). Usually the pituitary gland gets signals (from messengers such as inhibin B) that the testicles are making less sperm than they should, and it responds by increasing FSH in the bloodstream to tell the testicles to make more sperm. Sometimes, however, the FSH response from the pituitary gland is blunted, in that it does not produce more FSH in response to decreased testicular sperm production. [Esteves SC. RBMO 2024]. In these circumstances (normal FSH levels, decreased sperm density), studies have shown increases in semen parameters with the use of exogenous FSH therapy. [Behre HM. FrontEndocrin 2019] Official AUA/ASRM guidelines report some potential benefits (including increased pregnancy rates) for the treatment of idiopathic male fertility in men with normal or slightly elevated FSH levels. [Schlegal PN. FertSteril 2021]. Higher dosages of FSH have been associated with greater degrees in improvements in some studies, but there are also increased medication costs with this approach as well. [Caroppo E. FertSteril 2023].
Not everyone with normal FSH levels and oligospermia responds to exogenous FSH therapy. Studies have attempted to identify markers (such as serum 17-alpha-hydroxy-progesterone levels) to better predict response to this therapy, but so far there are no definitive predictive tests. [Cannarella R. FertSteril 2023] I feel a reasonable candidate would be a patient with normal or mildly increased FSH with a significantly low sperm density (despite correction of other risk factors). The normal FSH dosage I use in these men is 150 IU three time a week. In men with baseline normal FSH, low testosterone, and oligospermia, I usually recheck FSH levels after treatment with a SERM and/or anastrazole. Therefore if the patient remains oligospermic and his FSH is still fairly normal, they may be a candidate to try exogenous FSH therapy.