Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors. Letrozole possesses the longest required window of time for blood plasma levels to reach optimal peak out of all three major aromatase inhibitors (conversely, Arimidex and Aromasin require 7 days in order for optimal peak blood plasma levels to be reached). Always remember that the idea with the use of aromatase inhibitors is to control Estrogen levels and bring them back to normal physiological levels as opposed to the complete reduction and/or elimination of them, which will cause problems in the body. This is a breast cancer condition in which the diagnosis indicates that it is unknown as to whether or not Estrogen is the culprit, or whether or not the breast cancer is aggravated by Estrogen. Remember that the reason for the use of an aromatase inhibitor should at all times be for the purpose of Estrgen control rather than Estrogen elimination, as the complete and total reduction of all Estrogen levels in the body can and does result in deleterious effects on the human body. Letrozole is classified under pregnancy category X; hence caution should be used when administering this medication to a patient. Ovarian hyperstimulation syndrome is a relatively rare side effect of letrozole, which is characterized by a large ovarian mass, weight gain, nausea, vomiting, severe abdominal discomfort, and decreased urine output . Letrozole is usually well tolerated, with headaches, nausea, cramps, hot flashes, and exhaustion being the most common adverse effects. Letrozole is a potent and selective aromatase inhibitor that inhibits intracellular aromatase activity. Letrozole typically encourages the growth of a single follicle and prevents multiple pregnancies since it does not suppress the estrogen of the hypothalamic-pituitary-ovarian axis negative feedback. It might be an excellent decision in terms of cost-effectiveness analysis and patient acceptance. In such a situation, Letrozole might possibly be the best aromatase inhibitor to use above all other AIs at a full dose utilized by a competitive athlete only days leading up to a competition for the physique altering reasons previously stated. As Estrogen levels decline, the physique may take on more of a harder ‘grainier’ and ‘ripped’ look due to the loss of water retention provided by Estrogen. One important note to make with Letrozole doses is that it in fact takes 60 days before blood plasma levels of Letrozole have reached its optimal peak level, even though its half-life is approximately 2 – 4 days. One can easily conclude, based on the data provided, that Letrozole would be an effective addition to the necessary increases in Testosterone required during the post-cycle weeks following cessation of anabolic steroid use. One randomized, placebo controlled study by Loves et al looked at clinical and psychologic changes with obese, hypogonadal men who were give placebo or letrozole. While the literature is robust with improvement of hormone levels, there is a lack of data showing clinical improvement. Bone health may benefit from increased testosterone, but may also deteriorate from lack of estradiol. The conversion of testosterone to estradiol in the gonads has been predicted to be the cause of an increased testosterone/estradiol (T/E) ratio. Estrogen effects on the gonadotropins and testosterone have led to the evaluation of estrogen as a potential target for treating hypogonadism. In this study, the authors further demonstrated that the improvement in biochemical parameters were similar to that of exogenous testosterone at a much lower cost to the patient (14). Adverse events on BMD were an early concern, but one study of patients on CC greater than 12 months showed improved bone densitometry scores throughout the 3-year follow up period (11). The decline of testosterone levels has been implicated in the pathogenesis of physical frailty in older men. It is well known from experimental evidence and from clinical observations that estradiol has powerful effects on gonadotropin release in men. These case reports illustrate the important contribution of estrogens to male health and identify the possible indications and risks of aromatase-inhibitor treatment in men. This approach proved successful in rare conditions such as the aromatase-excess syndrome and high estrogen levels due to Sertoli cell tumors in boys with Peutz-Jeghers syndrome . Moreover, the mean baseline testosterone levels in the treated groups were in, or only slightly below, the normal range for young adult men and the relative increase in testosterone levels may have been too small. Treatment with atamestane 100 mg once daily resulted in a 40% increase in total testosterone levels after 36 weeks. Androgen treatment, therefore, has been advocated for older men with signs and symptoms of androgen deficiency and unequivocally low plasma testosterone levels 34,35. Aromatase inhibitors, therefore, have been suggested as a tool to increase testosterone levels in men with low testosterone levels. In men third-generation aromatase inhibitors will decrease the mean plasma estradiol/testosterone ratio by 77% 28,29. In most studies utilizing aromatase inhibitors in men estradiol levels decreased only moderately. Treatment resulted in normalization of testosterone levels in all subjects, with a concomitant suppression of the originally increased levels of estradiol. In three small studies, letrozole or testolactone has been administered to morbidly obese men to improve their testosterone levels 42-44. These observations outline a serious limitation of the use of aromatase inhibitors in older men; the stimulating effect on testosterone levels may be too weak, especially in the men with the lowest baseline testosterone levels who would potentially benefit most. Additionally, misuse of aromatase inhibitors is unlikely since testosterone levels will not be stimulated to vastly supraphysiological levels. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone-oestradiol ratio? In a recent comparison study done on HCG and different forms of testosterone, it was noted that HCG leads to a lesser increase in estrogen than exogenous testosterone.
