Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia

Loves, Sandra; Jong, J.D. de; Sorge, Adriaan van; Telting, Darryl; Tack, Cees J.; Hermus, A.R.M.M.; Boer, H. de

doi:10.1530/eje-13-0190

Cited by 34 publications

(44 citation statements)

References 38 publications

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“…A recent study in healthy men whose hypothalamus-pituitary-testis axis was suppressed by a gonadotropin releasing hormone agonist, comparing testosterone administration with an aromatase inhibitor with testosterone alone showed that estrogens are important for decreasing fat mass and contribute to maintenance of sexual function (Finkelstein, et al , 2013). Studies in hypogonadal men administered aromatase inhibitor showed while serum testosterone was increased and serum estradiol was suppressed , spine bone mineral density was decreased when estradiol was suppressed to very low levels (Burnett-Bowie, et al , 2009) but was unchanged when estradiol was kept at the lower limit of the reference range (Loves, et al , 2013). Because endogenous production of estrogens is suppressed by DMA administration, the long term effects of this androgen on bone health, fat mass, and other estrogen-dependent processes will need to be carefully assessed in future longer term clinical trials of DMAU.…”

Section: Discussionmentioning

confidence: 99%

Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive

et al. 2014

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The novel androgen, dimethandrolone (DMA) has both androgenic and progestational activities, properties that may maximize gonadotropin suppression. We assessed the pharmacokinetics of dimethandrolone undecanoate (DMAU), an orally bioavailable, longer-acting ester of DMA, for male contraceptive development. Our objective was to examine the safety and pharmacokinetics of single, escalating doses of DMAU (powder in capsule formulation) administered orally with or without food in healthy men. We conducted a randomized, double-blind Phase 1 study. For each dose of DMAU (25 to 800 mg), ten male volunteers received DMAU and two received placebo at two academic medical centers. DMAU was administered both fasting and after a high fat meal (200–800 mg doses). Serial serum samples were collected over 24h following each dose. DMAU was well tolerated without significant effects on vital signs, safety laboratory tests or electrocardiograms. When administered while fasting, serum DMA (active compound) was detectable in only 4/10 participants after the 800mg dose. When administered with a 50% fat meal, serum DMA was detectable in all participants given 200mg DMAU and showed a dose-incremental increase up to 800mg, with peak levels 4 to 8h after taking the dose. Serum gonadotropins and sex hormone concentrations were significantly suppressed 12h after DMAU administration with food at doses above 200mg. This first-in-man study demonstrated that a single, oral dose of DMAU up to 800 mg is safe. A high-fat meal markedly improved DMAU/DMA pharmacokinetics.

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Section: Discussionmentioning

confidence: 99%

Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive

et al. 2014

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“…Aromatase inhibitors (e.g., letrozole and anastrozole) decrease conversion testosterone to estrogen reducing the negative feedback on pituitary LH production. The higher LH levels stimulate the production of endogenous testosterone in men with residual hypothalamic-pituitary function, for example, aging and obesity [150-152]. Neither of these classes of drugs is approved by the FDA for treatment of male hypogonadism.…”

Section: Treatment Options For Patients With Secondary Hypogonadismentioning

confidence: 99%

An update on male hypogonadism therapy

Surampudi

Swerdloff

Wang

2014

Expert Opinion on Pharmacotherapy

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Introduction Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Areas covered Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Expert opinion Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.

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“…Several placebo controlled studies have been documented showing statistically significant increases in biochemical parameters (25,26). While the literature is robust with improvement of hormone levels, there is a lack of data showing clinical improvement.…”

Section: Aromatase Inhibitors (Ai)mentioning

confidence: 99%

Off label therapies for testosterone replacement

DiGiorgio

Sadeghi‐Nejad

2016

Transl. Androl. Urol.

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The incidence of hypogonadism has been steadily increasing over the last few years. Exogenous testosterone has been the standard treatment for hypogonadal men, but is associated with suppression of spermatogenesis as well as other possible adverse effects. There are other medications, currently considered “off label” for androgen replenishment, that exert their effect through modulation of the hypothalamic-gonadal axis. These medications increase endogenous testosterone levels and offer a different therapeutic approach. This review will focus on these alternative (off-label) therapies for androgen replacement in men.

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Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia

Cited by 34 publications

References 38 publications

Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive

Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive

An update on male hypogonadism therapy

Off label therapies for testosterone replacement

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