The hormone testosterone is undoubtedly a major driving force when it comes to human function and endeavor. On the one hand it has led to bold initiatives that have resulted in human prosperity and achievement. On the other hand however, it has also prompted many ill-conceived and even foolish urges and actions that have ended in misfortune, heartache and even in disater.Similarly, when it comes to reproductive function testosterone effects have likewise been a mixed bag. Consider the following:

1. Both male and female libido is in large part driven by testosterone. In the man, hypotestosteronism causes impotence and a lack of sex drive, while in the female, the production and the local release of testosterone by the ovaries also profoundly influences female libido.

• Neither ovarian follicle growth and development nor the production of estrogen could occur without the availability of the body’s own testosterone. The hormone is produced by the connective tissue (stroma) surrounding follicles from which it is delivered in a “bucket brigade” fashion to cells that line the inside of the follicle (granulosa cells). There, enzymatic digestion triggered by follicle stimulating hormone (FSH) converts testosterone to estrogen (mainly estradiol). This causes granulosa cells to proliferate, follicles to grow in size, and eggs housed in such follicles to undergo development and differentiation. At the same time, blood estrogen levels rise progressively. Thus, without access to ovarian testosterone, human reproduction would come to a halt.
  However, it is also true that too much testosterone delivered to follicles (as commonly occurs in older women who have diminished ovarian reserve and women with polycystic ovarian syndrome or PCOS), can lead to exhaustion of granulosa cells, compromised egg development and poor egg and embryo quality. It is all about a delicate balance that involves regulation of ovarian testosterone production. Since this is regulated by luteinizing hormone (LH), it follows that when it comes to ovarian stimulation with fertility drugs, it is important to properly control (down regulate) the amount of LH administered and or produced immediately prior to and during stimulation.

• Everyone knows that male hormones (predominantly testosterone) act peripherally to increase muscle mass. Such peripheral activity is dependant upon the conversion of testosterone to a more active form known as dihydrotestosterone. This is why body builders use androgen type hormones (anabolic steroids) in order to maximize muscle growth, bulk and definition. But testosterone also suppresses body’s own pituitary LH which is necessary for adequate testicular sperm production which in turn results in reduced sperm production (spermatogenesis) and serves to explain why overuse of such synthetic, commercial products can lead to a reduction in sperm production and even to testicular atrophy. It is come as no surprise therefore, that many bodybuilders and other athletes who overindulge in the use of such synthetic hormones often end up with male infertility.

Another point of interest is that testosterone also works centrally at the level of brain synapses where it promotes libido (in both men and women) by being converted enzymatically to estrogen. Unfortunately, many synthetic commercially available androgen products (e.g. Dianabol) inhibit this conversion, thereby explaining why many athletes that use such products experience decreased libido.

Clearly, when it comes to treating women undergoing IVF (especially those with ovarian stromal overgrowth) it is important to maintain body’s own LH at a low level prior to and throughout the stimulation cycle. To do so it is necessary administer fertility drugs that are low in LH-like activity. Clomiphene citrate (Serophene) and letrozole (Femara) tend to cause the pituitary gland to release much LH while injectable gonadotropin fertility drugs such as Menopur and Repronex contain about as much LH-like activity as they do FSH.

Also, drugs like Lupron, Buserelin, Nafarelin and Synarel (agonists), elicit a profound increase of the body’s own (pituitary) LH. Thus when agonists are used they need to be administered several days before initiating stimulation so as to exhaust the woman’s own LH and allow the levels of this hormone to drop and thereupon be sustained at negligible concentrations before beginning stimulation. When the administration of agonists is initiated at the start of ovarian stimulation (microflare protocols), the LH levels rise rapidly, causing increased ovarian testosterone production at the very time that follicle and egg development starts. This has the potential of adversely affecting the quality of eggs in that cycle.

Also, since women with stromal overgrowth commonly have high LH activity, the use of protocols where an antagonist (Cetrotide, Ganirelix, Orgalutron) that blocks LH release is first administered 6-7 days after ovarian stimulation has been initiated, should in my opinion also be used with caution (especially in women with stromal overgrowth). The reason is that by the time LH release is controlled through their use, some degree of irreversible egg damage for that cycle might have already occurred.

One of the great travesties still being perpetuated by some doctors, is the indiscriminate administration of testosterone to infertile men in the erroneous belief that it will improve sperm production. Nothing could be further from the truth.

When it comes to reproduction, testosterone can truly be regarded as being the “root of both good and evil”. Its role in promoting reproductive objectives is indisputable but its therapeutic role can be fraught with hazard. It is as well that those desiring to conceive understand the dynamics involved in this delicate balance.