Male Infertility

Hormone Abnormalities

The most common hormonal abnormality we treat in men with fertility problems is a low testosterone level, also referred to as hypogonadism. Hypogonadism can be caused by a defect in production of LH (the hormone that drives testosterone production), referred to as hypogonadotropic hypogonadism, or it can be from a failure of the testis to respond to adequate LH levels with enough testosterone (normogonadotropic or hypergonadotropic hypogonadism.) Both conditions can be treated with medications.

Hypogonadotropic Hypogonadism

This condition is due to the lack of the hypothalamic decapeptide gonadotropin-releasing hormone (GnRH), When associated with midline defects such as anosmia, it is called Kallmann’s syndrome. These men are usually diagnosed because they do not go through puberty. Very low or undetectable serum levels of LH, FSH and T in a prepubertal appearing adult confirms the diagnosis. Treatment for the development of secondary sexual characteristics and maintenance of libido used to be to give testosterone injections to provide hormones that allow secondary sexual characteristics to develop (facial, pubic and axillary hair growth, penile development, deepening of the voice, etc.) When these men tried to have children later, it was commonly found that their testes had not developed and their ability to produce sperm was very limited.

We have changed the paradigm for these young men. When detected in adolescence, we now give these men human chorionic gonadotropin (hCG), typically 1500-2500 IU 3 times weekly to drive the testes to grow and optimize their potential for later sperm production. The window of potential testicular growth is typically from years 13-22, so it is important to consider this hCG therapy before the window for testicular growth closes. Although this condition of Kallman syndrome is rare, optimizing fertility potential for these men is a recognized opportunity that we provide for the young men we follow and treat.

Normogonadotropic Hypogonadism

This condition is reflected by the presence of low testosterone with adequate/normal levels of LH. Men are usually found to have low sperm counts as well. Before treatment, more involved hormone testing is sometimes done to assure that there is no other condition that could cause low testosterone, such as a pituitary tumor. In these men, we use medications that encourage the body to make more LH and testosterone, taking advantage of the observation that men sense their testosterone levels by the circulating level of estrogens (usually measured as estradiol.) So blocking estrogen receptors (with clomiphene) or knocking down estrogen production (with an aromatase inhibitor) can allow increased testosterone production. We were the first to describe treatment of a large group of infertile men with low testosterone using aromatase inhibitors (anastrozole; Raman et al, https://www.auajournals.org/doi/10.1016/S0022-5347%2801%2969099-2). Common drugs used for this purpose include clomiphene citrate 25 mg daily (1/2 tab), or anastrozole 1 mg daily.

Followup hormone blood tests are done to evaluate the response to treatment, allowing dose adjustment to individualize this treatment.

Hypergonadotropic hypogonadism

Even men with low testosterone levels associated with elevated FSH and LH levels can have successful medical treatment to increase testosterone and sperm production. Often an elevated FSH may be associated with a lack of sperm in the ejaculate (azoospermia.) We have found that the men who respond to medical treatment are more likely to have sperm found with surgery (Reifsnyder et al., https://pubmed.ncbi.nlm.nih.gov/19616796/., https://pubmed.ncbi.nlm.nih.gov/22704105/ )

Treatment for these men may include hCG injections with anastrozole.

Men receiving testosterone therapy who are interested in fertility

Testosterone therapy, given as gels or injections, can dramatically reduce sperm production and cause infertility. The exogenous testosterone tricks the man’s body into believing that there is enough testosterone in the circulation, so the man stops making LH, and subsequently stops making testosterone and therefore stops sperm production. Indeed, testosterone has been used as a male contraceptive. We do not recommend that men take testosterone when interested in fertility, but occasionally we see men who are already taking these gels or injections and have difficulty stopping their treatment since their body is used to the high levels of testosterone resulting from this treatment. In such cases, we can increase internal testosterone production by giving hCG injections, or in some cases, by using anastrozole or another aromatase inhibitor to enhance internal testosterone production.

Consult with Dr. Schlegel

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