For both men and women, an alternative to testosterone replacement is low-dose clomifene treatment, which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects that can result from direct hormone replacement therapy.  This therapy has only been shown helpful for men with secondary hypogonadism. Recent studies have shown it can be safe and effective monotherapy for up to 2 years in patients with intact testicular function and impaired function of the HPTA( http:///ijir/journal/v15/n3/full/ ). Clomifene blocks estrogen from binding to some estrogen receptors in the hypothalamus, thereby causing an increased release gNRH and subsequently LH from the pituitary. Clomifene is a Selective Estrogen Reuptake Modulator (SERM). Generally clomifene does not have adverse effects at the doses used for this purpose. Clomifene at much higher doses is used to induce ovulation and has significant adverse effects in such a setting.
A 31-year-old man presenting with an 18-month history of sexual dysfunction resulting from severe adult-onset IHH (LH U/L, FSH U/L, T nmol/L). Initial therapy with 50 mg of clomiphene citrate (CC) three times a day for 7 days, with overnight LH pulse profiling and 9 am T levels evaluated at baseline and on completion. A 2-month washout period, followed by low-dose maintenance therapy (25-50 mg/d) for 4 months.
MAIN OUTCOME MEASURE(S):Baseline and stimulated T levels and LH pulsatility; effect on sexual function.
RESULT(S):Clomiphene therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function. CONCLUSION(S):Isolated hypogonadotropic hypogonadism may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate endogenous T secretion and enhance fertility potential. On theoretical grounds, reversal of gonadotropin deficiency with CC might be expected to have a similar biological effect.
The concentrations of serum total and free testosterone were studied in 30 healthy, middle-aged men during a dietary intervention program. When men were transferred from their customary diet to an experimental diet, which contained less fat with a higher polyunsaturated/saturated ratio (P/S-ratio) and more fibre, there was a significant decrease in serum total testosterone concentrations ( +/- vs +/- nmol/l SEM, P less than ). Furthermore, serum free, unbound testosterone fell from +/- to +/- nmol/l SEM (P less than ). The hormonal changes were reversible. This observation suggests that testosterone activity in plasma can at least partly be modified by changing the composition of the diet.