Over the past 15 years it has become evident that in men estradiol is responsible for a number of effects originally attributed to testosterone. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect. A prospective study by KK Women’s and Children’s Hospital (KKH) has found Letrozole, an aromatase inhibitor, to be safe and effective for the treatment of men with low sperm count of unknown cause.
The lowering of estradiol by AIs has been shown to increase the levels of LH, FSH and testosterone (25). It is unclear at this point whether higher increases in testosterone via aromatase inhibition would help counteract the negative consequences of lower estradiol. Men with estrogen deficiency caused by a mutation in the CYP19 gene suffer from low BMD, unfused epiphyses, and have high gonadotropin and testosterone levels.
Letrozole is also approved for the treatment of post-menopausal female breast cancer patients that are exhibiting symptoms of Estrogen receptor unknown breast cancer. It is also approved for the extended treatment for post-menopausal female breast cancer patients after 5 years of Nolvadex administration. Letro is approved by the FDA for the treatment of post-menopausal female breast cancer patients as an adjunctive treatment when first-line treatments (such as Nolvadex) have failed to work. The T + AI combination implant seems to be a promising therapy that has the potential to simultaneously treat breast cancer, prevent side effects of chemotherapy, and improve health and quality of life in breast cancer survivors. This case report also supports previous data on the safety and efficacy of the combination T + AI on quality of life in breast cancer survivors.6 These preliminary findings may stimulate interest in further research on the prevention of chemotherapy-induced toxicities, and also the treatment of menopausal symptoms in millions of breast cancer survivors worldwide.
Although testosterone induces growth velocity, the estrogens aromatized from testosterone will accelerate epiphysial maturation and for that reason reduce adult height further. Boys with a mean age of 11 years at the start of the study were treated with letrozole 2.5 mg once daily or placebo for 2 years . In an earlier study a combination of spironolactone and testolactone proved effective , whereas in later studies the combination of bicalutamide and anastrozole was used 57-59. Aromatase inhibitors, therefore, may be used to lower estradiol levels and thereby slow down epiphysial maturation. Uncontrolled studies using anastrozole, testolactone or letrozole have shown some evidence for a positive effect on sperm concentration and motility 49-51. Aromatase inhibition results in a three-fold increase in levels of FSH 28,29 in eugonadal men and may potentially stimulate sperm production. Although FSH release is primarily under the control of inhibin, circulating estradiol has a substantial effect on FSH levels in men .
The oocyte does not fully mature until after the luteinizing hormone spike. Luteinizing hormone is essential for supporting the dominant follicle's ultimate maturation in the later stages of follicle development. (b) The impact of estrogen on the pituitary's production of FSH. The ovary's physiological functions include timely ovulation and estradiol and progesterone production.
The authors also noted an increase in vitamin D which they hypothesized may be the reason for maintenance of semen parameters. Their primary endpoint was a 20% increase in muscle mass measured as peak torque (PT) by isokinetic dynamometry in the knee and shoulder joints. In this randomized double blind placebo study, 40 men received either 250 µg (5,000 IU) r-hCG or placebo. As with other off label medications for testosterone replacement, the efficacy of HCG is not well replicated in treating symptomatic adult onset hypogonadism.
A case study describes a morbidly obese infertile man, who after a similar treatment with anastrozole showed a normalized pituitary-testis axis, spermatogenesis and fertility . Finally, the decreased levels of estradiol may have affected the expected rise in lean body mass . A small, controlled study demonstrated that anastrozole in a dose of 1 mg daily during 12 weeks will result in doubling of the mean bioavailable testosterone level in older men . Therefore aromatase inhibitors have been tested in older men suffering from so-called late-onset hypogonadism or partial androgen deficiency. Due to their mode of action the use of aromatase inhibitors is limited to men with at least some residual function of the hypothalamo-pituitary-gonadal axis.
Androgens, including T, are candidates for such treatments since they modulate immune function.30,32-34 Novel cancer therapeutic strategies focus on supporting the immune system. Although the data on nolvadex are conflicting,21 preclinical evidence does not support this concern for T. The patient had no signs or symptoms of cardiac toxicity or compromise.

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