来曲唑-芳香化酶抑制剂讲解

Clinical use
We present the case of an infertile man with small testes and an elevated FSH level, which was diagnosed as NOA, hypospermatogenesis proven by testicular biopsy. After taking letrozole for 3 months, semen analyses by computer-aided sperm analysis present that this man had normal spermatogenesis.
Spermatogenesis
Increase gonadotropin secretion stimulate Leydig and Sertoli cell function
stimulate sperm production
Clinical use
• We investigated whether letrozole (2.5 mg per day) improves sperm count in NOA patients. 4 men were included in this study, and they had FSH and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months.
Aromatase activity
It has been demonstrated in:
gonads placenta brain fat tissue muscle hair bone vascular tissue
Estradiol production
Nonsteroidal enzyme inhibitors such as anastrozole and letrozole inhibit enzy源自文库e activity by binding with the heme iron of the enzyme.
Incomplete efficacy
In postmenopausal women with breast carcinoma, long-term use of potent aromatase inhibitors reduces circulating estradiol levels by 88% and is associated with adverse effects on bone.
Epiphysial closure
Lower estradiol levels and thereby slow down epiphysial maturation.
Aromatase inhibitors, mostly combined with agonists of GRH proved effective for the prevention of premature epiphysial closure in boys with pubertas praecox.There is also evidence that aromatase inhibitors can be used in boys with idiopathic short stature and boys with constitutional delay of puberty to increase adult height.
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% .
Clinical use
The study group consisted of 29 infertile men with a low serum T/E2 ratio (<10). Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months.
Aromatase inhibitors in men
概要
1
Background
2
Aromatase
3
Aromatase inhibitors
4 Effects of aromatase inhibitior
5
Safety and concerns
Background
The role of estradiol
CYP19 gene
Men with estrogen deficiency caused by a mutation in the CYP19 gene suffer from：
I. low bone mineral density (BMD) II. unfused epiphyses, III. high gonadotropin IV. high testosterone levels .
Clinical use
2 of the 10 oligospermic men (20%) achieved spontaneous pregnancy after the letrozole treatment. In 4 of 17 azoospermic men (23.5%), spermatozoa appeared in the ejaculate with a mean total motile sperm counts of 1.11 ± 0.69 million, although 13 men (76.5%) remained azoospermic after letrozole treatment.
gaining and maintaining bone mass closing of the epiphyses the feedback on gonadotropin secretion
Estrogen excess
premature closure of the epiphyses gynecomastia low gonadotropin low testosterone levels.
Cause of incomplete efficacy
Aromatase is less suppressed in the testis compared to adipose and muscle tissue.
Advantage
It prevents excessive reduction of estrogen levels in men and the possible associated adverse effects.
Clinical use
We investigated the effect of letrozole, an aromatase inhibitor, on body mass index, serum hormones, and sperm parameters in infertile men with decreased T/E2 ratios.
Aromatase
5/30/2019
Aromatase
Aromatase, also known as estrogen synthetase, is the key enzyme in estrogen biosynthesis. The enzyme, localized in the endoplasmic reticulum of the estrogenproducing cell, is encoded by the CYP19A1 gene， which is localized on chromosome 15 and comprises nine exons， the start codon for translation is located on exon 2.
Clinical use
All patients suffered losses of libido despite the supra-physiological levels of T,FSH and LH; however, in a study on the sexual behaviour of men with aromatase congenital deficiency, a loss of libido occurred even with supra-physiological levels of testosterone.This suggests that oestrogens could have a role in supporting libido.
Safety and concerns
• Long-term use in postmenopausal women is associated with a moderate increase in bone resorption and a modest decrease in BMD compared with placebo.
Effects of aromatase inhibitior
Effect
Lowering estradiol levels, by administering an aromatase inhibitor such as letrozole, is associated with an increase in levels of LH, FSH and testosterone through the feedback of hypothalamo-pituitary-gonadal axis.
direct testicular secretion conversion of testicular androgens peripheral conversion of adrenal androgens
Aromatase inhibitors
5/30/2019
Mechanism
Clinical use
The increase in average TFSF in the letrozole group after treatment compared with the pretreatment value was 31.6%, and the increase in average TFSF in the anastrazole group after treatment compared with the pretreatment value was 21.1%.