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Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects.

ABSTRACT: Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes). Design: Randomized double-blind placebo-controlled pilot trial. Methods: Twenty-three obese men (BMI?35 kg/m2), 35-65 years old, were randomized to weight loss (diet and exercise) plus either anastrozole (AI+WL, n = 12) at 1 mg daily or placebo (PBO+WL, n = 11) for 6 months. Inclusion criteria: total testosterone <300 ng/mL (average of 2 measurements), estradiol?10.9 pg/ml, LH <9 IU/l. Symptoms of hypogonadism by questionnaires; muscle strength by Biodex dynamometer; body composition and bone mineral density by dual-energy X-ray absorptiometry; bone microarchitecture and finite element analysis by high resolution peripheral quantitative-computed tomography. Results: After 6 months of therapy, AI+WL group had higher testosterone (p = 0.003) and lower estradiol (p = 0.001) compared to PBO+WL. Changes in symptoms and muscle strength did not differ between groups. AI+WL resulted in higher fat mass loss than PBO+WL (p = 0.04) without differences in changes in lean mass. Total and LDL cholesterol reduced more in the PBO+WL group compared to AI+WL (p = 0.03 for both), who experienced a minimal increase with unlikely meaningful clinical impact. Tibial trabecular bone area decreased more in PBO+WL than AI+WL group for which it remained stable (p = 0.03). Conclusions:Although AI+WL is effective in reversing the hormonal profile of HHG in severely obese men without causing major side effects, it does not lead to greater improvements in muscle strength and symptoms of hypogonadism compared to WL alone. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02959853.

SUBMITTER: Colleluori G

PROVIDER: S-EPMC7243137 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects.

Colleluori Georgia G Chen Rui R Turin Christie G CG Vigevano Francesca F Qualls Clifford C Johnson Biju B Mediwala Sanjay S Villareal Dennis T DT Armamento-Villareal Reina R

Frontiers in endocrinology 20200515

<b>Objective:</b> In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary ...[more]

PMID: 32499757

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Project description:PurposeIn both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obese men scheduled for bariatric surgery.MethodsHypogonadal patients with consistent symptoms (n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal (n = 17) or asymptomatic hypogonadal (n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies.ResultsIn TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TTh men also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones.ConclusionsThe present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged.Clinical trial registrationClinicalTrials.gov Identifier: NCT02248467, September 25th 2014.

Project description:Objective(s)To characterize for the first time the side effect profile, safety, and tolerability of hormonal contraception among women receiving opioid-agonist therapy.Study designWe conducted a secondary analysis of data collected from participants in a three-arm randomized controlled trial (N = 138) aimed at increasing effective contraceptive use among women receiving opioid-agonist therapy. Participants in the 2 intervention conditions (n = 90) had free access to hormonal contraception at each of the 14 visits scheduled during the 6-month intervention. Contraceptive use and side effects were recorded at each visit; participants could change methods or discontinue use at any time. Verbatim side effects were classified using Medical Dictionary for Regulatory Activities (MedDRA) terminology.ResultsOf 67 participants reporting hormonal contraceptive use, 29 (43%) initiated implants, 14 (21%) intrauterine devices, 13 (19%) combined pills, 11 (16%) progestin-only pills, 10 (15%) injectables, 1 (2%) ring, and 1 (2%) patch; the average (±standard deviation) duration of use was 129 ± 55, 129 ± 60, 108 ± 62, 102 ± 61, 111 ± 31, 145, and 18 days, respectively. A total of 321 side effects were reported by 55 (82%) participants. Fifty (75%) participants reported menstrual cycle changes/uterine bleeding, followed by headaches (16, 24%), weight gain (15, 22%), and abdominal pain or nausea/vomiting (11, 16%). No serious side effects were reported. Twelve participants (18%) changed methods and 13 (19%) discontinued all hormonal contraceptive use.Conclusion(s)The hormonal contraceptive side effects reported by this small group of women receiving opioid-agonist therapy appear consistent with those reported by the general population, was generally well-tolerated, and did not raise safety concerns.ImplicationsThese results provide important preliminary evidence that hormonal contraceptive use produces a familiar side effect profile and is well-tolerated by women receiving opioid-agonist therapy, although studies with larger samples followed over longer periods of time with appropriate comparison conditions are needed to fully assess tolerability and safety.

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Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects.

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Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects.

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