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The benefits and risks of androgen therapy in the aging male: prostate disease, lipids and vascular factors
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
The first results of studies wherein testosterone itself was administered to mildly hypogonadal aging men were comforting. In a double-blind, placebo-controlled, crossover study Tenover17 found that administering testosterone enanthate (100 mg per week) for 3 months to 13 healthy elderly men with low serum total and non-sex hormone binding globulin bound testosterone levels, decreased total and low density lipoprotein (LDL) cholesterol without changing HDL cholesterol. In agreement with these results are the findings of Morley and colleagues16. Administration of 200 mg testosterone enanthate every 2 weeks for 3 months decreased total cholesterol without changing HDL cholesterol levels. Of great interest is the study of Ellyin47 establishing, in a 2-year study of administration of testosterone cypionate (25 mg per week or 50 mg every 2 weeks) to elderly mildly hypogonadal men, a decrease in total and LDL cholesterol and no change in HDL cholesterol and triglycerides.
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
The AASs, like the endogenous androgens, have a four-ringed backbone structure with 19 carbon atoms (Figure 6.1). Modifications of this androstane backbone have been introduced to prolong the metabolic half-life and thus the efficacy of synthetic AASs. Three main classes of AASs have been described.2,3 The first, used primarily as injectable compounds, is derived from esterification of the 17P-hydroxyl group of testosterone and includes testosterone propionate and testosterone cypionate. Esterification retards absorption and prolongs the duration of action after injection of the hormone by slowing its release into circulation. Testosterone esters can be hydrolyzed into free testosterone, reduced to 5α-dihydrotestosterone, an androgen with higher biological activity at brain androgen receptors than testosterone,20-22 or aromatized to estrogens21 (for review, see Kochakian and Yesalis22). Molecules that have been 5α-reduced cannot be metabolized into estrogens but may be metabolized into other androgenic compounds such as 3a-androstanediol.
Polyendocrine Syndromes
Published in Jack L. Leahy, Nathaniel G. Clark, William T. Cefalu, Medical Management of Diabetes Mellitus, 2000
Repeated phlebotomy may reverse the hypogonadism. This primarily occurs in men younger than 40 years. Otherwise, hypogonadism can be treated with testosterone replacement. Testosterone per se cannot be effective administered orally; the testosterone congeners that are administered by mouth are associated with a risk of hepatic dysfunction, and should be avoided in hypogonadal patients in general (and certainly in the patient with hemochromatosis who is likely to have significant liver disease already because of the underlying disorder). Testosterone can be effectively restored by intramuscular injection of long-acting agents, such as testosterone enanthate or testosterone cypionate, either of which can be administered at a dose of 200 mg every 2 weeks. This will result in serum levels in the normal physiological range for men after a steady state is achieved following the initial rise after the injection. Alternatively, testosterone can be administered by transdermal systems (patches), with a typical dose being one 5 mg patch to be replaced daily.
Important lessons about testosterone therapy- weight loss vs. testosterone therapy for symptom resolution, classical vs. functional hypogonadism, and shortterm vs. lifelong testosterone therapy
Published in The Aging Male, 2020
Efficacy and safety were demonstrated in two other dose-response studies that achieved testosterone levels of 900 ng/dL or higher [18,20,27]. A recent small RCT in healthy men, aged 25–55 years, with normal serum total testosterone levels showed that treatment with high dose testosterone gel (up to 15 g per day) for 12 weeks - achieving testosterone levels of 1150 ng/dL (40 nmol/L) - did not adversely affect lipids, glucose or insulin, while resulting in the expected dose-dependent increase in LBM and decrease in fat mass [20]. Impact on hematocrit and PSA was not reported. A 6-month RCT by Dhindsa et al. demonstrated the safety of achieving serum testosterone levels of 780 ng/dL (by treatment with 250 mg testosterone cypionate every 2 weeks for 24 weeks) [26]. Likewise, the 3 year long testosterone RCT by Basaria et al. – the longest RCT to date – showed that achieving a testosterone level of 22.5 nmol/L (650 ng/dL) is safe [28].
Safety of testosterone therapy in men with prostate cancer
Published in Expert Opinion on Drug Safety, 2019
Abraham Morgentaler, Monica Caliber
Additional promising results using BAT have been reported in other populations. The BATMAN trial evaluated the safety and efficacy of BAT in patients with asymptomatic hormone-sensitive PCa with low metastatic burden or non-metastatic biochemically recurrent disease [118]. Testosterone cypionate or enanthate was administered intramuscularly (IM) at the dose of 400 mg every 28 days (day 1, 29, and 57), a dose/schedule shown to generate a rapid rise in serum testosterone levels to the supraphysiologic range (>1500 ng/dL) 2 days post-injection, with a decline to near castrate level (100 ng/dL) 28 days post-injection. ADT was continued throughout the study to allow rapid cycling from near castrate to supraphysiologic range T following T injections. Results showed the primary endpoint was met, with 17/29 men (59%, 90% confidence interval: 42-74%) having PSA <4 ng/mL at 18 months. QoL improved following the first cycle of BAT, as measured by the SF-36, FACT-P, and IIEF surveys [118].
Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer – recent developments and future directions
Published in Expert Opinion on Investigational Drugs, 2018
Pedro Isaacsson Velho, Michael A. Carducci
The BAT approach was first tested in a pilot study [61] in patients with asymptomatic CRPC. The BAT treatment was paired with oral etoposide, based on the rationale that DHT (dihydrotestosterone) could generates transient double strand DNA breaks (DSBs) in CRPC cells through the recruitment of AR and topoisomerase IIβ to androgen response elements [62,63]. This study enrolled 16 patients to initially receive testosterone cypionate 400 mg intramuscularly on day 1 and etoposide 100 mg on days 1–14 of each cycle, repeating cycles every 28 days. This dose and formulation of testosterone was chosen because it produces supraphysiologic testosterone levels (>1500 ng/mL) within the first days after injection and a subsequent decline to high-normal testosterone levels after 2 weeks, and return to near-castrate testosterone levels by 28 days [64]. This study demonstrated that BAT associated with etoposide is active in PCa, showing a decline in PSA in 50% (7/14) of patients, with 28.6% (4/14) having a PSA decline ≥50%. Of the 10 patients who had evaluable soft tissue metastases, 50% had radiographic responses (4 PR and 1 CR), 30% had stable disease. It is important to notice that only 20% of patients had progressive disease, but no patient developed urinary obstruction, new or worsening pain, or skeletal events, demonstrating that this therapy is safe in patients with metastatic PCa. This study also showed that the majority of side effects were caused by etoposide (nausea, fatigue, alopecia, edema, and neutropenia), favoring that the next studies evaluate BAT alone.