NCT03490513

Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism

Completed Phase 4 Last updated 7 August 2025

What this trial tests

Phase 4 trial testing anastrozole (1 mg/day) in Hypogonadism, Hypogonadotropic in 121 participants. Completed in 31 May 2025.

Timeline

15 April 2018

Primary endpoint
31 May 2025

31 May 2025

Quick facts

Lead sponsor	Baylor College of Medicine
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	121
Start date	15 April 2018
Primary completion	31 May 2025
Estimated completion	31 May 2025
Sites	1 location across United States

Drugs / interventions tested

• anastrozole (1 mg/day) — full drug profile →
• Placebo

Conditions studied

• Hypogonadism, Hypogonadotropic — all drugs for Hypogonadism, Hypogonadotropic →
• Obesity — all drugs for Obesity →

Sponsor

Baylor College of Medicine

Who can join

Adults 40 to 65, male only, with Hypogonadism, Hypogonadotropic or Obesity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The investigators have preliminary data suggesting that obese patients with hypogonadotropic hypogonadism (HHG) have minimal benefit from testosterone therapy likely because of its conversion to estradiol by the abundant aromatase enzyme in the adipocytes. The increased conversion of androgens into estrogens in obese men results in a negative feedback of high estradiol levels on hypothalamus and pituitary, inhibiting the production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) and, as a consequence, of testosterone by the testis. Testosterone administration could increase estradiol production, further promoting the inhibitory feedback to the hypothalamic-pituitary-gonadal axis. Although weight loss from lifestyle modification has been shown to reduce estradiol and increase testosterone levels, the effect is at best modest and weight regain results in recurrence of hypogonadism. The use of aromatase inhibitors, in combination with weight loss, could be an effective alternative strategy due to its action at the pathophysiology of the disease.

Intervention Subjects (body mass index of ≥35, testosterone \<300 ng/dl) will be randomized to the active (anastrozole) or control (placebo) group. Anastrozole 1 mg tablet / day will be self-administered with or without food, at around the same time every day (active group); placebo 1 tablet/day with or without food to take at around the same time every day (control group). The study duration will be 12 months.

Both groups will undergo lifestyle intervention consisting of diet and supervised exercise program. Target weight loss will be at least 10% of baseline body weight during the intervention. Subjects will attend weekly group behavior modification sessions which will last \~75-90 min for the first 3 months and decreased to every two weeks from 3 to 12 months. Subjects will attend supervised research center-based exercise sessions during the first 6 months followed by community fitness center-based sessions during the next 6 months for at least 2 d/wk, with recording of home-based exercises for the other 2-4 days/week.

Although the above original protocol requires the participants to come to our center for dietary and exercise training, since the Covid19 pandemic, study participants were given the following options for lifestyle intervention: 1) in-person visits at our facility for dietary classes and exercise training, 2) to enlist in the gym of their choice with membership paid for by the study, or 3) virtual method of lifestyle intervention. These amendments were put in place due to Covid 19 restrictions; however, we decided to keep these methods because most of our subjects prefer them over coming for in-person visits at our lab even after COVID restrictions were lifted. Since the study had just the first 25 subjects enrolled prior to COVID outbreak, majority of the subject's lifestyle interventions were done by virtual dietary classes every week for the first 3 months and then every 2 weeks thereafter either as a group or by one-on-one sessions. Exercise program was also supervised by exercise physiologist virtually or by phone for subjects who want to exercise at a community gym

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength and Low Bone Turnover.
   Vigevano F, Gregori G, Colleluori G, Chen R, et al · · 2021 · cited 44× · PMID 33537757 · DOI 10.1210/clinem/dgab061
2. One-Year Mean A1c of > 7% is Associated with Poor Bone Microarchitecture and Strength in Men with Type 2 Diabetes Mellitus.
   Ballato E, Deepika FNU, Russo V, Fleires-Gutiérrez A, et al · · 2022 · cited 13× · PMID 35665818 · DOI 10.1007/s00223-022-00993-x
3. Health implications of racial differences in serum growth differentiation factor levels among men with obesity.
   Bathina S, Lopez VF, Prado M, Ballato E, et al · · 2024 · cited 1× · PMID 39668628 · DOI 10.14814/phy2.70124
4. Lifestyle Intervention Therapy Modulates Global DNA Methylation and Adipogenic Gene Expression in Severely Obese Hypogonadal Men.
   Bathina S, Fuenmayor Lopez V, Prado M, Teo SB, et al · · 2026 · PMID 41893347 · DOI 10.3390/metabo16030198
5. MON-707 Lifestyle Intervention Therapy Modulates Global and Gene Specific DNA Methylation In Severely Obese Hypogonadal Men
   · 2025
6. MON-706 Metabolic Saviour or Muscle Menace : The Unresolved SGLT2 Inhibitor Paradox
   · 2025
7. MON-709 Fibro-inflammatory Stromal Cells Produce Atrophy-inducing Paracrine Factors in a Mouse model of Diabetes-associated Sarcopenia
   · 2025
8. 6669 Association Between Serum Levels of Thyroid Function and Per- and Polyfluoroalkyl Compounds Concentrations in Central Precocious Puberty in Girls
   · 2024