Suppression of testosterone

An important qualification must be made. While a biomarker may be of proven value in establishing whether a drug has the desired effect in patients or healthy volunteers (see Section 4.6.3) and for evaluation of the dose-response relationship, a biomarker may not be a surrogate for the clinical endpoint. Thus, suppression of testosterone after an initial rise will give an almost immediate endpoint for the effect of GnRH analogues in prostate cancer but the relationship breaks down later in the disease. Measures of blood glucose control are vital... 

Gynecomastia was occasionally observed in men when ketoconazole first became available. Ketoconazole has a marked effect on steroid concentrations, including a change in the testosterone/estradiol ratio, and this is most likely to be the basis of the gynecomastia. A lowering of testosterone serum concentrations and a reduced response of testosterone concentrations to human gonadotropin have been shown (SED-11, 573) (583). Various studies have shown suppression of testosterone, androste-nedione, and dehydroepiandrosterone, with reciprocal increases in gonadotrophins. 

Make sure that stud males are caged alone for several weeks prior to caging with females to prevent suppression of testosterone by dominant males in the same cage, which lowers plugging efficiency. 

Spherical microspheres of PLG with relatively low surface porosity and particle size in the 17 p, range were formulated to contain a luteinizing hormone, releasing hormone antagonist, Orntide, for the suppression of testosterone, e.g., in patients with prostatic carcinoma. In vitro release studies showed a sustained release of the peptide for at least 30 days. Elevated blood levels of the peptide were observed for about 28-30 days and testosterone was suppressed for at least 30-35 days in an animal model. No initial increase of the blood level of testosterone was observed and the onset of suppression of testosterone occurred within 6 h. 

B2. Bardin, C. W., Hembree, W. C., and Lipsett, M. B., Suppression of testosterone and androstenedione production rates with dexamethasone in women with idiopathic hirsutism and polycystic ovaries. J. Clin. Endocrinol. 28, 1300-1306... 

Ketoconazole also suffers from a number of other clinical disadvantages. At daily doses greater than 400 mg ketoconazole may reversibly inhibit endogenous steroid synthesis with resultant suppression of testosterone and... 

Researchers discovered that MPA also had effects on men. When injected into a man, MPA accelerates the metabolism of testosterone while also suppressing its production. The result is a reduction of up to 75 percent in the amount of testosterone in the man s body, thus lowering the intensity of inappropriate sexual cravings and the frequency of unacceptable erotic pre-... 

Hormone implants can be used for long-term stimulation or suppression of odor production. Scent marking is stimulated by testosterone in gerbils and wolves (Asa etal., 1990). 

Anabolics are testosterone derivatives (e.g., clostebol, metenolone, nan-drolone, stanozolol) that are used in debilitated patients, and misused by athletes, because of their protein anabolic effect. They act via stimulation of androgen receptors and, thus, also display androgenic actions (e.g., virilization in females, suppression of spermatogenesis). 

Human prolactin is similar in structure to human growth hormone, and both are good lactogens. In women, prolactin acts with other hormones on the mammary gland during pregnancy to develop lactation and after birth to maintain it. Hyperprolactinemia causes impotence in men and amenorrhea and infertility in women. Chronically elevated levels of circulating prolactin are associated with suppression of 17-p-estradiol and testosterone production in the ovaries and testes. 

The concomitant intake of grapefruit juice increases the concentration of many drugs (e.g., testosterone, sildenafil) in humans. Such actions appear to be mediated mainly by the suppression of the cytochrome P450 enzyme CYP3A4 in the small intestine. The resultant diminished first-pass metabolism and increased bioavailability can lead to increased drug levels in the blood. Because sildenafil is metabolized by CYP3A and to a... 

Handelsman DJ, Wishart S, Conway AJ (2000) Oestradiol enhances testosterone-induced suppression of human spermatogenesis. Hum Reprod, 15(3) 672-679. 

In the early mammalian female embryo the absence of the Mullerian inhibitory substance MIS permits continuing development of the Mullerian duct, while the absence of testosterone permits the Wolffian duct to degenerate. However, positive developmental signals are also required. Among these is the protein Wnt-4, a member of a large family of locally acting signal molecules (Section 4). Wnt-4 may be needed both for oocyte development and for further suppression of male development.261... 

Severe consequences can occur from defective syn- thesis of a steroid hormone, as is the case in several metabolic diseases. Patients who have 21-hydroxylase deficiency are unable to convert progesterone to aldosterone and cortisol. Instead the progesterone is directed to an excess production of testosterone. In the female, this results in masculinization and hirsutism (growth of hair). In the male, premature masculinization occurs. If the disease is diagnosed before the first birthday, the patient can be treated with the missing steroid hormones, which in turn suppress the synthesis of excess progesterone and, as a consequence, testosterone via feedback mechanisms. 

Bebb RA, Anawalt BD, Christensen RB, Paulsen CA, Bremner WJ, Matsumoto AM. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone a promising male contraceptive approach. J Clin Endocrinol Metab 1996 81(2) 757-62. 

---