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Although aromatase inhibition by anastrozole and letrozole is reported to be close to 100%, administration of these inhibitors to men will not suppress plasma estradiol levels completely. In men third-generation aromatase inhibitors will decrease the mean plasma estradiol/testosterone ratio by 77% [28,29]. This finding probably relates to the high plasma concentrations of testosterone, a major precursor for estradiol synthesis in adult men. As aromatase inhibition is dose dependent it has been suggested that aromatase is less suppressed in the testis compared to adipose and muscle tissue, explaining the incomplete efficacy of aromatase inhibition in men. Aromatase activity is high in the testes and the molar ratio of testosterone to letrozole is much higher in the testes compared with adipose and muscle tissue. When testicular testosterone and estradiol synthesis are suppressed and testosterone is administered exogenously in combination with letrozole, however, the estradiol/testosterone ratio is suppressed by 81% [30], which is only marginally different from the suppression of this ratio in intact men after treatment with letrozole. This incomplete suppression may be regarded as advantageous for it prevents excessive reduction of estrogen levels in men and the possible associated adverse effects. In postmenopausal women with breast carcinoma, long-term use of potent aromatase inhibitors reduces circulating estradiol levels by 88% [31] and is associated with adverse effects on bone [2,3]. Due to the much higher estrogen levels in treated men it remains to be determined whether this also holds true for men.
Aromatase inhibitors in men: effects and therapeutic options
The daily use of 2.5 mg letrozole was associated with a decline of the mean serum estradiol concentration of 56%.
Under normal conditions, only 10–20% of circulating estradiol is directly secreted by the testes; the remaining 80% is the product of peripheral aromatization of testosterone or conversion of estrone (20). The adrenal glands also contribute to circulating estradiol levels, through the production of estrone and androstenedione, which can be converted to estradiol and testosterone, respectively
In Men, Peripheral Estradiol Levels Directly Reflect the Action of Estrogens at the Hypothalamo-Pituitary Level to Inhibit Gonadotropin Secretion | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic
Placebo or letrozole (2.5 mg daily, Femara; Novartis AG, Stein, Switzerland) orally taken on awakening were administered in random order each day for a 28-d period
Letrozole was well tolerated and lowered serum E2 by 46% in the young men (P = 0.002) and by 62% in the elderly men (P < 0.001) (Table 2) and comparably over the two study periods; serum E1 was lowered by 31% (P = 0.01) and by 50% (P < 0.001) in the young and the elderly, respectively
Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic
Ten severely obese men, mean age 48.2 ± 2.3 (s.e.) years and body mass index 42.1 ± 2.6 kg/m2, were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week.
Six weeks of treatment decreased serum estradiol from 120 ± 20 to 70 ± 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 ± 0.8 to 14.8 ± 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 ± 1.0 to 23.8 ± 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone-binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response.
Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism
Aromatase inhibitors in men: effects and therapeutic options
The daily use of 2.5 mg letrozole was associated with a decline of the mean serum estradiol concentration of 56%.
Under normal conditions, only 10–20% of circulating estradiol is directly secreted by the testes; the remaining 80% is the product of peripheral aromatization of testosterone or conversion of estrone (20). The adrenal glands also contribute to circulating estradiol levels, through the production of estrone and androstenedione, which can be converted to estradiol and testosterone, respectively
In Men, Peripheral Estradiol Levels Directly Reflect the Action of Estrogens at the Hypothalamo-Pituitary Level to Inhibit Gonadotropin Secretion | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic
Placebo or letrozole (2.5 mg daily, Femara; Novartis AG, Stein, Switzerland) orally taken on awakening were administered in random order each day for a 28-d period
Letrozole was well tolerated and lowered serum E2 by 46% in the young men (P = 0.002) and by 62% in the elderly men (P < 0.001) (Table 2) and comparably over the two study periods; serum E1 was lowered by 31% (P = 0.01) and by 50% (P < 0.001) in the young and the elderly, respectively
Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic
Ten severely obese men, mean age 48.2 ± 2.3 (s.e.) years and body mass index 42.1 ± 2.6 kg/m2, were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week.
Six weeks of treatment decreased serum estradiol from 120 ± 20 to 70 ± 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 ± 0.8 to 14.8 ± 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 ± 1.0 to 23.8 ± 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone-binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response.
Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism
