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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
As for the other steroidal aromatase inhibitors, testolactone is thought to exert its anticancer effect by inhibiting aromatase-mediated estrone synthesis from adrenal androstenedione, the major source of estrogen in postmenopausal women. Furthermore, based on in vitro studies, the aromatase inhibition is noncompetitive and irreversible which presumably accounts for the persistence of inhibition of estrogen synthesis after withdrawal of treatment.
Endocrinology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Mehul Dattani, Catherine Peters
The precocious puberty can be difficult to control. Agents used include cyproterone acetate, medroxyprogesterone and aromatase inhibitors (testolactone, letrozole, anastrozole), but they are all of limited efficacy. Abnormalities of other endocrine glands are treated as and when the problems arise (e.g. bilateral adrenalectomy for Cushing syndrome, carbimazole for thyrotoxicosis).
Systematic review of hormone replacement therapy in the infertile man
Published in Arab Journal of Urology, 2018
Amr El Meliegy, Ahmad Motawi, Mohamed Ahmed Abd El Salam
Testolactone, as an aromatase inhibitor, has been shown to be effective in alleviating infertility as a result of hypogonadotrophic hypogonadism of obese men at a dose of 1 g daily for 6 weeks [44]. On the other hand, Raman and Schlegel [45] have conducted a study on a total of 140 subfertile men with abnormal testosterone-to-E2 ratios of <10:1 to evaluate the effect of administration of anastrozole at a dose of 100–200 mg daily on hormone profiles as well as semen parameters in non-obstructive azoospermic patients who presented with normal or decreased levels of testosterone and elevated levels of E2. Anastrozole treatment was found to be effective in normalising the testosterone-to-E2 ratio and total testosterone levels, thus improving semen parameters.
Pharmacological management of late-onset hypogonadism
Published in Expert Review of Clinical Pharmacology, 2018
Giulia Rastrelli, Mario Maggi, Giovanni Corona
AIs prevent androgens from being converted into estrogens by aromatase. They are classified into steroidal (testolactone and exemestane) and nonsteroidal (anastrozole and letrozole). While testolactone is not commercially available, exemestane, anastrozole, and letrozole are currently used for treatment of breast cancer in women. In men, the reduction in estrogen levels has been hypothesized as a possible mechanism for increasing T levels without blunting Gns [27,28,31,32]. This characteristic allows us to hypothesize their clinical application for improving spermatogenesis and fertility and for increasing T levels in HG men, particularly those with obesity-related SHG.
What must be considered when prescribing hormonal pharmacotherapy for male infertility?
Published in Expert Opinion on Pharmacotherapy, 2022
Olivia Holtermann Entwistle, Aditi Sharma, Channa N. Jayasena
A systematic review examining the effect of AIs on men with primary testicular failure examined eight randomized and non-randomized studies [18]. Enrolled patients were all hypogonadal, indicated by a serum testosterone-to-estradiol ratio (T/E2) of <10. The review found that treatment with AIs, such as anastrozole, letrozole, or testolactone, significantly increased testosterone levels and the T/E2 ratio and that oligospermic men had a significant increase in sperm concentration from baseline [18]. Azoospermic participants did not respond in three of the included studies [18]. However, in one included study, azoospermic men treated with letrozole produced sperm in the ejaculate [18]. Side effects included subclinical hepatic failure, urticarial rashes, and loss of libido (Table 2) [18]. The follow-up period was too short to capture any potential negative impacts on bone mineral density, a documented side effect of AIs. Pregnancy outcomes were not assessed. No incidences of venous thromboembolic (VTE) disease were documented in the meta-analyses examining SERMs or AIs [16–18], however, data drawn from studies of women taking SERMs and AIs for the management breast cancer suggest that VTE is a serious potential side effect of such treatments [19,20]. Although, a recent study examining VTE risk in men undergoing hormonal treatment for hypogonadism, including those taking clomiphene citrate, concluded that the VTE risk was low [21], there remains a paucity of data on this side effect in men [9,21]. In view of this, and the potential seriousness of VTE, this risk should be discussed with patients and efforts made to minimize risk from other factors such as smoking and obesity, and particular caution employed in prescribing anti-estrogen therapies to men with preexisting, unmodifiable risk factors for VTE, such as Klinefelter’s syndrome [9]. The limited number of studies, short follow-up period, lack of standardization of treatment regimens, and the varying quality of their methodologies means firm conclusions cannot be drawn from the current data.