来曲唑-芳香化酶抑制剂

of these inhibitors to men will not suppress plasma
estradiol levels completely. In men third-generation
aromatase inhibitors will decrease the mean plasma
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% and is associated with adverse effects on bone.
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. • In most studies utilizing aromatase inhibitors in men estradiol levels decreased only moderately.
gonads placenta brain fat tissue muscle hair bone vascular tissue
Estradiol production
direct testicular secretion
conversion of testicular androgens
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.
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%.
activity by binding with the heme iron of
the enzyme.
Incomplete efficacy
Although aromatase inhibition by anastrozole and
letrozole is reported to be close to 100%, administration
and testosterone through the feedback of
hypothalamo-pituitary-gonadal axis.
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
gynecomastia
low gonadotropin
low testosterone levels.
Aromatase
9/3/2015
Aromatase
Aromatase, also known as estrogen synthetase, is
the key enzyme in estrogen biosynthesis. The enzyme,
gaining and maintaining bone mass closing of the epiphyses
the feedback on gonadotropin secretion
Estrogen excess
premature closure of the epiphyses
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
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.
localized in the endoplasmic reticulum of the estrogen-
producing cell, is encoded by the CYP19A1 gene，
which is localized on chromosome 15 and comprises
estradiol/testosterone ratio by 77% .
Cause of incomplete efficacy
Aromatase is less suppressed in the
testis compared to adipose and muscle
tissue.
Advantage
peripheral conversion of adrenal androgens
Aromatase inhibitors
9/3/2015
Mechanism
Nonsteroidal enzyme inhibitors such as
anastrozolyme
nine exons， the start codon for translation is located on
exon 2.
CYP19 gene
Men with estrogen deficiency caused by a mutation in the CYP19 gene suffer from：
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.
I.
low bone mineral density (BMD)
II. unfused epiphyses, III. high gonadotropin IV. high testosterone levels .
Aromatase activity
It has been demonstrated in:
evidence that aromatase inhibitors can be used in boys with
idiopathic short stature and boys with constitutional delay of puberty to increase adult height.
Spermatogenesis
Increase gonadotropin secretion stimulate Leydig and Sertoli cell function