Antiandrogenic effects

Borch J, Axelstad M, Vinggaard AM, Dalgaard M (2006) Diisobutyl phthalate has comparable antiandrogenic effects to di-n-butyl phthalate in fetal rat testis. Toxicol Lett 163 183-190... 

Lee B, Koo H (2007) Hershberger assay for antiandrogenic effects of phthalates. J Toxicol Environ Health Part A 70 1365-1370... 

They have a low incidence of adverse reactions and the reactions that occur are generally mild. Rapid intravenous infusion of H2 antagonists may cause bradycardia. Cimetidine is more inclined to cross the blood-brain barrier and CNS effects such as somnolence and confusion have been described, especially in the elderly and in patients with impaired renal function. Cimetidine in high doses, as the only one of its class, has antiandrogenic effects which could be explained by an increase of prolactin secretion, binding to androgen receptors and inhibition the cytochrome P450 mediated hydroxylation of estradiol. 

Because of its effectiveness in blocking C17-20 lyase activities, ketoconazole does not enhance existing hirsutism associated with metyrapone. On the other hand, the antiandrogenic effects of ketoconazole may prove disconcerting to male patients. 

B. Finasteride is a 5a-reductase inhibitor, which essentially makes dihydrotestosterone unavailable to the prostate but does not reduce serum testosterone levels. The decreased prostatic levels of dihydrotestosterone frequently result in a size regression of the prostate, while the relatively normal testosterone levels minimize a depressed libido. Flutamide and spironolactone exhibit antiandrogen effects by competing for the androgen receptor ketoconazole inhibits testosterone synthesis and stanozolol is an oral anabolic androgen preparation. 

Saw palmetto extract can inhibit the enzyme 5-a-reductase in vitro. This enzyme converts testosterone into dihydrotestosterone (DHT), which in turn contributes to prostatic enlargement. Saw palmetto also appears to have an antiinflammatory effect and can reduce DHT binding to prostatic androgen receptors (antiandrogenic effect). Despite its proposed 5-a-reductase mechanism. 

Isotretinoin is a retinoid, recently approved for use in capsule form (10-20 mg). It decreases the amount of sebum that sebaceous glands produce. Isotretinoin exhibits antiproliferative and antiandrogenic effects on the sebaceous glands. It also interacts with the formation of androgens in sebaceous glands. It is indicated in the treatment of severe nodular acne, acne conglobata and recalcitrant acne. It is available in International market under the brand name ACCUTANE by Roche pharmaceuticals. 

The widespread detection of phthalate metabolites in human urine has produced questions about public-health risks, especially with regard to antiandrogen effects that can influence male gonadal development (Gray et al. 2000 Parks et al. 2000). The extrapolation from urinary biomonitoring results to exposure and risk assessment has been facilitated by calculations that convert urinary metabolite concentrations to intake dose of the parent phthalate (Koo et al. 2002 Koch et al. 2003 Kohn et al. 2000 David 2000). The parent diester phthalates are rapidly and completely metabolized to the monoester metabolites, which are rapidly cleared by the kidney. Those features allow one to assume that the daily excretion rate of metabolite is equal to the daily intake rate of the parent chemical. Furthermore,... 

Spironolactone exhibits antiandrogenic effects in males and females. It decreases testosterone biosynthesis by inhibiting steroid 17a-monooxygenase (17a-hydroxylase) activity, possibly secondary to destruction of microsomal cytochrome P-450 in tissues with high steroid 17a-monooxygenase activity (testes, adrenals) [65],... 

Most developmental neurotoxicity studies have focused on general impairment of behaviour, but some studies have also found evidence for effects on sexual dimorphic behaviour. Hormones play a central role in central nervous system development, including the sexual differentiation of the brain. Studies on hormones and various endocrine disrupting chemicals (particularly those with estrogenic or antiandrogenic effects) have shown that the developing brain may be susceptible to disturbances in sexual behaviour. Therefore, effects on one sex but not the other should not be dismissed, but must be evaluated in the context of effects on sexual differentiation of the brain. 

Song LN, Coghlan M, Gelmann EP. Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor. Mol. Endocrinol. 2004 18 70-85. 

A possibly unique case of alopecia affecting the entire body was described in 1981 in that case the temporal association was convincing and there was a correlation with an antiandrogenic effect on hormone concentrations (26). 

Famotidine is a histamine H2 receptor antagonist. It does not affect drug metabolism and it has been claimed to be free of the antiandrogenic effect of cimetidine however in one woman who accidentally took double doses of the drug for some months it did cause hyperprolactinemia and breast engorgement (SEDA-18, 372). In other ways it bears a very close resemblance to cimetidine for example, headache and confusion with intravenous use are reported, as are thrombocytopenia and pancytopenia (SEDA-15, 395). 

Antiandrogenic effects have been associated with several phthalates)63] as well as with PCBs, dioxins, and organochlorine pesticides, chemicals that have been associated with diabetes prevalence in adult men)64,65 Mixtures of phthalates and other antiandrogens have been shown to act in an additive manner in animal studies, I66 67 and in a greater than additive manner in one human study)68 ... 

Many commonly used drugs have sympatholytic, anticholinergic, sedative, or antiandrogenic effects that may exacerbate or contribute to the development of erectile dysfunction. Clinicians should be familiar with these agents and be prepared to make adjustments in drug regimens to minimize adverse effects of these drugs on a patient s erectile function. 

Saw palmetto s benefits in treatment of BPH are hypothesized to be due in part to antiandrogen effects (Wilt et al., 1998). Saw palmetto is a multisite inhibitor of androgen action. In an in vitro study (Briley et al., 1983), a liposterolic saw palmetto extract called Permixon was shown to compete with... 

Corvol, P., Michaud, A., Menard, J., Freifeld, M. and Mahoudeau, J. (1975) Antiandrogenic effect of spirolactones mechanism of action. Endocrinology, 97, 52-58. 

Long, B.J., D.N. Grigoryev, I.P Nnane, Y. Liu, Y.Z. Ling, and A.M. Brodie (2000). Antiandrogenic effects of novel androgen synthesis inhibitors on hormone-dependent prostate cancer. Cancer Res. 60, 6630-6640. 

Eplerenone is a selective aldosterone receptor blocker devoid of antiandrogenic effect. 

D. Toxicity Cimetidine is a potent inhibitor of hepatic drug-metabolizing enzymes and may also reduce hepatic blood flow. Cimetidine also has significant antiandrogen effects in patients receiving high doses. Ranitidine has a weaker inhibitory effect on hepatic drug metabolism neither it nor the other H, blockers appear to have endocrine effects. 

Ranitidine is associated with antiandrogenic effects in some patients... 

Causes inhibition of hepatic metabolism of many drugs some antiandrogenic effects... 

D. Combined Oral Contraceptives Combined oral contraceptives exert an antiandrogenic effect when they are used in women with hirsutism that is due to excess production of androgenic steroids. The estrogen in the contraceptive acts in the liver to increase the production of sex hormone binding globulin (SHBG), which in turn acts to reduce the concentration of free androgen in the blood. 

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