In a relatively small number of cases of male infertility, the failure to produce an adequate quality of sperm relates to reduced secretion by the pituitary gland of those hormones necessary to stimulate sperm production. The pituitary gland in the man produces two important hormones-identical to those produced by women-that control testicular function. The first is follicle stimulating hormone(FSH) and the second is luteinizing hormone (LH). Luteinizing hormone’s predominant function is to act on a particular variety of cells in the testicles that produces the male hormone testosterone. These cells are referred to as Leydig cells. A sustained reduction in FSH production, therefore, is capable of resulting in male infertility. Usually, if there is a reduction in either one of the components, LH or FSH, the other one will also be low. In other words, if a man produces a normal amount of LH and has normal male hormone levels (testosterone, androstenedione, dehydroepiandrosterone), then it is very unlikely that he will have a reduced FSH production. Accordingly, if his sperm function is reduced, it is unlikely to be the result of reduced FSH production by the pituitary gland.
The woman’s cycle usually lasts about 28 days, and under normal circumstances, results in the release of one egg per menstrual cycle. In the man, there exists a continuous production of sperm. In fact, the entire cycle, from initiation to the production of a mature sperm that is capable of fertilizing an egg, takes approximately 100 days. Accordingly, any treatment administered to the man in order to improve sperm production can only be properly assessed after waiting for a period of approximately 100 days. In men, the pituitary gland releases FSH and LH daily in order to meet this need; this is in contrast to the day to day variation that controls the menstrual cycle.
In order to assess the potential of a male to respond to fertility drugs aimed at stimulating the testicles to produce more spermatozoa and/or male hormone, it is necessary to first measure FSH and LH as well as prolactin and the male hormones testosterone, androstenedione and dehydroepiandrosterone. Measurement of these hormones gives an indication of the likelihood that a male patient will respond to:
Treatment aimed at inducing increased production of FSH or FSH/LH (e.g., Clomiphene Citrate)
The direct administration of gonadotropins which comprise FSH, LH or HCG:
FSH: Follistim, Puregon, Gonal F, Bravelle
FSH+LH: Menopur, Repronex
hCG: Pregnyl, Profasi, Ovidrel
Clomiphene citrate is a hormone which, through its central action in the brain, stimulates the pituitary gland to produce natural FSH in large amounts. The FSH, in turn, as mentioned above, stimulates spermatogenesis. The treatment is very simple and involves the administration of 25mg of Clomiphene citrate every other day for a period of 100 days. After performing a baseline semen analysis, FSH, LH, and male hormone measurements immediately prior to initiating therapy, and then to serially repeated throughout the treatment with Clomiphene. The final assessment of response can only be made approximately 100 days after initiating therapy. This administration of Clomiphene is essentially harmless to the man. He may experience some minor side effects such as dryness of the mouth, headaches, slight changes in mood and, rarely, hot flashes. These side effects are all reversible upon discontinuation of therapy.
In cases where Clomiphene therapy fails to be successful, or in certain situations where it is not possible for Clomiphene to stimulate the pituitary gland into action, it is possible to administer FSH alone (Follistim, Gonal F, Bravelle) or as combined FSH+LH (e.g. Menopur, Repronex) in the hope of stimulating the testicles directly. This therapy may be combined with the administration of the hormone human chorionic gonadotropin (HCG), which is also a natural hormone and mimics the effects of LH. In men the HCG is administered in order to stimulate the production of testosterone. Administration of these drugs is usually carried out 3 times per week, for a period of about 100 days before optimal response can be determined. The treatment is, again, relatively harmless and minimal side effects. Like clomiphene, the benefits will be lost when the medications are stopped as would any side effects.
Other Hormonal Therapies
There is very little evidence that vitamins, amino acid preparations or specific male hormone administration would be of benefit except as supportive therapy in the treatment of male infertility. In some cases, there may be systemic conditions affecting other areas of the body which indirectly impact upon the pituitary gland’s ability to produce the hormones necessary to stimulate testicular function. Rare examples include administration of thyroid hormone in cases of involvement of the thyroid gland, severe diabetes mellitus, and collagen production diseases among others. Sometimes the pituitary gland produces too much of a hormone called prolactin, which can inhibit the production and activity of FSH and LH to act on the testicles. In such cases, it may be necessary to administer a drug called bromocriptine or a new longer-acting form called cabergoline, to suppress prolactin production, and thereby remove the restraining effect of prolactin. There are, of course, many other such examples of where treatment of unrelated conditions might improve overall male fertility since, in general, any condition that compromises health can diminish fertility. Testosterone is often prescribed erroneously in an attempt to improve sperm function. Such treatment is in fact contraindicated because prolonged use (more than 2-3 months) of testosterone will almost always have the opposite effect, compromising sperm count, motility and even morphology.
If the man is fortunate enough to respond to one of the above treatment modalities by sufficiently boosting his sperm production, then it is possible for a number of specimens of sperm to be collected and frozen in liquid nitrogen. These samples can be kept for a number of years, so there will always be relatively good quality sperm on hand, even if the fertility treatment is discontinued. Therefore men do not need to continue these treatments indefinitely.