TweetDRUG TREATMENT OF MALE INFERTILITY: Androgens: Testosterone is perhaps the most widely used drug in male infertility. The long-acting compounds like testosterone enanthate (Testoviron depot, Schering), or combinations of different esters (Sustanon, Organon) are now generally preferred. But each physician seems to have his own dose schedule and the results can be highly variable. It is now well recognised that a high local concentration of testosterone (about 80 times the blood concentration), aided by a specific Androgen-Binding-Protein in the seminiferous tubules, is the most important stimulus for spermatogenesis. Small doses of exogenous testosterone (e.g. 50 mg fortnightly) which are carried to the testes after dilution in the blood stream may, therefore, produce little improvement in sperm count. On the other hand, large doses (e.g. 250 mg weekly) tend to depress the pituitary, thereby inhibiting spermatogenesis. To choose the correct dose has, therefore, been a problem. In this connection one can make use of the "rebound phenomenon" which often occurs when testosterone administration is stopped3. Testosterone propionate or enanthate, 100-200 mg/week for 10-12 weeks (the normal duration of one spermatogenetic cycle being about 80 days) will promptly bring down the sperm count to almost zero. It is better if counts are made at intervals of 3-4 weeks and the treatment stopped if azoospermia is obtained earlier. After nearly 5-6 months of stopping the testosterone, the sperm count shows a marked improvement over the initial level through a reactive hyperfunction of the pituitary. Considerable patience is, however, required both on the part of the patient as well as the doctor since this "rebound" may sometimes take almost an year to develop. The possibility of a prolonged or even permanent suppression of spermatogenesis in a small percentage of cases (2%), particularly with excessive dosage, must always be borne in mind9. Testosterone therapy should be given a trial in patients with oligospermia or poor motility and those in which biopsy shows maturation arrest and suppressed sperm formation but not atrophy. As is well known, testosterone is not effective orally. Newer oral androgens – Recently, mesterolone (Proviron, Schering) has been introduced as a highly effective oral androgen which can stimulate spermatogenesis without suppressing the pituitary. Although not marketed in India so far, our limited experience with 25-50 mg mesterolone daily for 2-3 months has given very encouraging results. The sperm count went up from 6 to 90 million in one patient. Another oral androgen, fluoxymesterone, has also been used in the dose of 5-20 mg daily with good results15. In particular, sperm motility seems to improve well with oral androgen therapy, perhaps through action on the epididymis where sperm maturation occurs. Gonadotropins: It has long been known that spermatogenesis is under control of the pituitary gonadotropins. However, it has only been realised in recent years that the two gonadotropins may stimulate spermatogenesis through a common mechanism of providing a high local concentration of testosterone: LH directly stimulates the Leydig cells which produce testosterone and FSH promotes the synthesis of a specific Androgen-Binding-Protein in the tubules. It is because of this that LH, available as Human Chronic Gonadotropin (Antuitrin-S, Parke-Davis) is much more effective in human infertility than FSH available as Post-Menopausal Gonadotropin or Pregnant Mare's Serum (Anteron, Schering). HCG in the dose of 1000-2000 IU twice a week for 10-12 weeks will often improve depressed spermatogenesis and could be followed by a course of testosterone, if needed. A proper selection of cases is, however, necessary because both when spermatogenesis is entirely absent or entirely normal, no benefit can be expected. Anti-estrogenic Drugs: Clomiphene citrate (Clomid), a weak anti-estrogen, has proved highly effective in inducing ovulation in women and has fully established its value in gynaecological practice. It increase the gonadotropin secretion, provided the pituitary is normally functioning, through competitive inhibition of the hypothalamic receptor sites which are responsible for the
normal androgen/estrogen feed-back mechanism. The use of clomiphene in the male to promote spermatogenesis has, however, been disappointing. A dose of 50-200 mg per day orally for 1-3 months of this costly drug could raise the sperm count only marginally and that too in a few of the patients only12. Its better use is for a diagnostic test of pituitary gonadotrophic function in the male. Vitamins: The role of vitamins in maintaining spermatogenesis in man is still a matter of controversy. Vitamin A deficiency damages the epithelium in general, and vitamin A deficient rats have shown atrophy of the germinal epithelium in the testis. Because of this known epitheliotropic action, large doses of vitamin A have been used for the treatment of male infertility. The effect seems to be entirely pharmacological, quite unrelated to any deficiency. The dose of vitamin A (Arovit, Roche; Aquasol-A, U.S. Vit. Pharm.) to be used is rather high: 50,000-1,50,000 IU for 1 to 3 months in idiopathic oligospermia or azoospermia. A paradoxical depression of spermatogenesis occurs at first but a significant improvement in the ejaculate often follows. This is almost similar to the rebound action with testosterone. The simultaneous administration of vitamin E and restricting the therapy to less than 6 months protects against any danger of hypervitaminosis2. The anti-sterility function of Vitamin E has been demonstrated only in laboratory animals, particularly the rat. It has, however, been used extensively in male infertility, although the deficiency of vitamin E has never been shown to be the cause of infertility in man. Vitamin E (Ephynal, Roche; E-toplex, U.S. Vit. Pharm.), 100 mg daily, can be given alone or along with vitamin A for 1-3 months to improve the number and motility of the sperms. But the use still remains largely empirical. Although there is no specific indication for the use of vitamin C in male infertility, 0.5-1.0 gm daily can sometimes be helpful in improving liquification of the semen and combating any infection. Vitamin B12 has often been used in combination with testosterone in male infertility. Some workers have postulated its role in spermatogenesis14 and Pardanani et al10 found low serum and seminal B12 levels in infertile patients. But there is little to suggest that a combination of small doses of testosterone with massive doses of B12, as often employed (Aquaviron-B12, Schering), has any advantage over testosterone therapy alone. Except, therefore, when B12 deficiency is clinically suspected, there is little to be gained from B12 administration in human infertility.