Hyperprolactinemia: An Uncommon But Known Cause of Male Infertility
In certain settings, the workup of male infertility may include a hormonal evaluation in order to determine if there is an abnormality of the HPG (Hypothalamic, Pituitary, Gonadal or testicular) axis. The basics of this axis are as follows: The Hypothalamus releases GnRH (Gonadatropin Releasing Hormone) which results in the pituitary release of FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone). These hormones in turn affect the Sertoli cells in the testis, regulating sperm production and the Leydig cells in the testis, regulating testosterone production.
Elevated prolactin levels can affect both sexual function and fertility through the suppression of the HPG axis. Persistently elevated prolactin suppresses production of GnRH which then slows down the whole system ultimately reducing production of testosterone as well as sperm. Presenting signs and symptoms may include decreased sex drive, difficulty with erections, gynecomastia and infertility correlating with reduced sperm production. Larger pituitary tumors can also cause local mass effects at the base of the brain causing headaches, visual field defects, and hypopituitarism extending to other hormones. Larger tumors are called “macroadenomas” and are defined a size greater than one centimeter in diameter.
First line treatment for prolactinomas is medical using dopamine agonists bromocriptine or cabergoline. These medications are effective 80-90% of the time. Refractory cases can be managed by surgery to remove the benign tumor.
Prolactinomas are the most common pituitary adenoma with a prevalence in male general population of 0.01%. Current AUA (American Urological Association) guidelines recommend prolactin testing when Testosterone is found to be low and secondary hypogonadism is suspected.
This Study was a retrospective review of all men presenting for initial male fertility evaluation from a single physician from 1999 to 2018 with respect to the incidence and prevalence of elevated prolactin.
Of 3101 men whose records were appropriate for review, 65 (2.1%) had hyperprolactinemia (Defined as a level above 18 ng/ml. The Median testosterone was found to be lower for these men compared to the remainder of the population (Median 280 vs 313), and they were found to have a lower total motile sperm count. Of the 65, 11 (17%) were diagnosed with a prolactinoma which translates to an incidence of 0.35% which is thirty-five times higher than in the general male population (0.1%). Three of these men who were treated went on to have natural conception.
There are other contributing factors which can explain elevation in prolactin. Men with increased LDL cholesterol and cardiovascular disease have higher risk, and the use of certain medications classified as antipsychotics and antidepressants may elevate levels. In addition, men with hypothyroidism or chronic renal insufficiency may have higher levels.
In this author’s practice, prolactin is evaluated according to AUA guidelines, ie when secondary hypogonadism is discovered. I typically diagnose a case of significant hyperprolactinemia every one to two years. In all cases that I have been witness to, treatment was successful with medical therapy.