Anastrozole for Obesity and Low Testosterone

Overseen By Reina Villareal, MD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: Baylor College of Medicine

Must not be taking: Bisphosphonates, Glucocorticoids, others

Disqualifiers: Diabetes, Prostate carcinoma, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether anastrozole, a medication, can help manage obesity and low testosterone in men. Researchers believe anastrozole might be more effective than testosterone therapy alone because it prevents testosterone from converting into estradiol, which can disrupt hormone balance. Participants will take either anastrozole or a placebo, alongside a weight loss program that includes diet and exercise. The trial seeks obese men with a BMI of 35 or higher and low testosterone levels. As a Phase 4 trial, this research aims to understand how anastrozole, already FDA-approved and proven effective, can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that affect hormone levels or bone metabolism.

What is the safety track record for Anastrozole?

Research has shown that anastrozole can increase testosterone levels in men with low testosterone. One study found that it helped older men reach normal testosterone levels. In overweight and obese men, anastrozole also increased testosterone and lowered estrogen levels.

While these results are encouraging, some reviews mention limited information about the long-term safety of anastrozole use in men. However, the trial's later stages suggest that earlier studies found anastrozole to be generally safe. Most people likely tolerate it well, but further information could confirm its long-term safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for obesity and low testosterone focus on lifestyle changes or hormone replacement therapy. However, Anastrozole is unique because it works by inhibiting aromatase, an enzyme that converts testosterone to estrogen. This mechanism can potentially increase testosterone levels, which is different from directly providing testosterone like many current treatments. Researchers are excited about Anastrozole because it not only targets hormonal balance but also integrates with behavioral and exercise programs to promote weight loss, potentially offering a comprehensive approach to managing these conditions.

What evidence suggests that anastrozole might be an effective treatment for obesity and low testosterone?

Research has shown that anastrozole can increase testosterone levels in men with low testosterone and a high body mass index (BMI). In studies, men taking anastrozole experienced a noticeable rise in testosterone and a drop in estradiol, a hormone that tends to increase in overweight men and can reduce testosterone production. For instance, one study found that about 95% of men treated with anastrozole had a significant increase in testosterone levels. In this trial, participants in one arm will receive anastrozole alongside a weight loss program. Another study showed that after six months, men taking anastrozole had higher testosterone and lower estradiol compared to those taking a placebo. Participants in the other arm of this trial will receive a placebo with the same weight loss program. These results suggest that anastrozole can help balance hormones and may improve symptoms of low testosterone in overweight men. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

Men aged 40-65 with severe obesity (BMI ≥35) and low testosterone (<300 ng/dl), who have symptoms of androgen deficiency. They must not have had recent weight fluctuations, diabetes with high blood sugar or A1C levels, bone diseases, heart problems, prostate cancer or very high PSA levels, among other exclusions.

Inclusion Criteria

I am a man with a BMI of 35 or higher.

Luteinizing Hormone (LH) of <9.0 mIU/L

You have symptoms that suggest low levels of male hormones, as determined by a questionnaire called the Androgen Deficiency in Aging Male (ADAM).

Exclusion Criteria

I do not have conditions that affect bone health like hyperparathyroidism or osteomalacia.

I do not have recent heart attacks, unstable angina, stroke, or severe heart failure.

condition that could prevent from completing the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either Anastrozole or placebo daily, along with a lifestyle intervention including diet and supervised exercise program

12 months

Weekly group behavior modification sessions for the first 3 months, then bi-weekly until 12 months; supervised exercise sessions for 6 months, then community-based sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole

Trial Overview The trial is testing if anastrozole (a drug that blocks estrogen production) combined with a weight loss program can help obese men with hypogonadism. Participants will either take anastrozole or a placebo daily for a year while following diet and exercise plans.

How Is the Trial Designed?

Group I: Weight loss plus anastrozole Experimental Treatment 1 Intervention

Participants will take Anastrozole 1mg per day, attend behavioral classes conducted by a dietitian, receive instruction on how to loss 10% of their body weight and undergo supervised exercise training program.

Group II: Weight loss plus placebo Placebo Group 1 Intervention

Participants will take a placebo every day, attend behavioral classes conducted by a dietitian, receive instruction on how to loss 10% of their body weight and undergo supervised exercise training program.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

In a study of 344 men, the combination of anastrozole and testosterone delivered via a subcutaneous implant effectively maintained low estradiol levels, preventing side effects associated with excess estrogen during testosterone therapy.

The therapy allowed for higher testosterone dosing and longer intervals between implant insertions, with no reported adverse events, indicating a safe and effective approach to managing hormone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Testosterone Anastrozole Therapy in Men: Rationale, Dosing, and Levels on Therapy. Glaser, RL., York, AE.[2019]

In a retrospective review of 117 advanced breast cancer patients treated with anastrozole, 59% showed either improvement or stable disease after treatment, indicating its efficacy even in patients with multiple prior therapies.

Patients with three or more prior endocrine therapies had a 61% response rate, and those with ER-negative tumors also benefited, suggesting that anastrozole can be effective in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Anastrozole in a Consecutive Series of Advanced Breast Cancer Patients Treated with Multiple Prior Chemotherapies and Endocrine Agents: M. D. Anderson Cancer Center Experience. Knoche, AJ., Michaud, LB., Buzdar, AU.[2019]

In a study of postmenopausal women with early-stage hormone receptor-positive breast cancer, those with a high body mass index (BMI > 35 kg/m²) experienced more recurrences compared to those with a low BMI (BMI < 23 kg/m²), indicating a poorer prognosis for obese women.

Anastrozole was found to have lower recurrence rates than tamoxifen across all BMI categories, but its relative efficacy appeared to be greater in thinner women, suggesting that different treatment strategies may be needed for overweight patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. Sestak, I., Distler, W., Forbes, JF., et al.[2022]

After 5 years of treatment with anastrozole, patients showed a significant increase in lumbar spine bone mineral density (BMD), with increases of 2.35% and 4.02% at years 6 and 7, respectively, indicating a positive effect on bone health.

In contrast, tamoxifen treatment resulted in a decrease in lumbar spine and total hip BMD, suggesting that anastrozole may be a safer option for maintaining bone density in patients compared to tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Eastell, R., Adams, J., Clack, G., et al.[2022]

In a study of 197 postmenopausal women with breast cancer, those treated with anastrozole experienced significant bone mineral density (BMD) loss over 5 years, with decreases of 6.08% in the lumbar spine and 7.24% in the total hip, compared to increases in BMD for those on tamoxifen.

Despite the bone loss associated with anastrozole, no patients with normal BMD at baseline developed osteoporosis, suggesting that while monitoring may be necessary for those with pre-existing bone issues, healthy patients may not need additional monitoring beyond standard recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. Eastell, R., Adams, JE., Coleman, RE., et al.[2022]

Anastrozole is more effective than tamoxifen in improving disease-free survival and reducing tumor recurrence in postmenopausal women with hormone receptor-positive early breast cancer, as shown in the ATAC trial with significant relative risk reductions of 17% and 19%.

Anastrozole has a better safety profile compared to tamoxifen, with lower rates of side effects such as vaginal bleeding, hot flushes, and thromboembolic events, while both treatments had similar impacts on patient quality of life during the first two years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: in early breast cancer. Wellington, K., Faulds, DM.[2018]

In a study of 80 boys aged 11-18 with persistent pubertal gynecomastia, anastrozole treatment resulted in a 38.5% response rate compared to 31.4% for the placebo, indicating no significant difference in effectiveness.

Anastrozole was well tolerated and led to a significant increase in the testosterone/estradiol ratio, suggesting it effectively alters hormone levels, but did not significantly reduce breast volume compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial. Plourde, PV., Reiter, EO., Jou, HC., et al.[2018]

In a study of 216 postmenopausal women with early-stage breast cancer, higher body mass index (BMI) was associated with increased plasma concentrations of the aromatase inhibitor anastrozole, suggesting that obesity may affect the drug's metabolism.

Women with obesity not only had 25% higher anastrozole levels compared to those of normal weight but also exhibited lower follicle stimulating hormone (FSH) levels, indicating higher estrogenic activity, which could impact treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does obesity interfere with anastrozole treatment? Positive association between body mass index and anastrozole plasma levels. Hubalek, M., Oberguggenberger, A., Beer, B., et al.[2018]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

In a retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

Anastrozole, an aromatase inhibitor, significantly reduced cell viability and proliferation in estrogen receptor-positive FM3A cells, indicating its potential effectiveness in treating estrogen-sensitive breast cancer.

The study identified a dose of 1μM as the most effective for inhibiting cell growth, with statistically significant results across all tested doses and time points, suggesting a strong antiproliferative effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of anastrozole on the proliferation of FM3A cells. Topcul, M., Cetin, I., Ozlem Kolusayin Ozar, M.[2018]

Anastrozole, an aromatase inhibitor, was found to be therapeutically effective in treating advanced breast cancer in postmenopausal women, with a response rate of 21.7% among 60 evaluable patients.

The treatment significantly suppressed plasma estradiol levels by 58.3%, and the main side effects, such as nausea and fatigue, were generally mild and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of anastrozole in the treatment of postmenopausal women with advanced breast cancer]. Feng, F., Xu, B., Jiang, Z.[2018]

Anastrozole is a highly effective aromatase inhibitor that significantly reduces plasma estrogen levels in both healthy individuals and postmenopausal breast cancer patients, achieving up to 98.1% inhibition of aromatization at higher doses.

In large randomized studies, anastrozole demonstrated comparable effectiveness to megestrol acetate in treating breast cancer, but with fewer side effects and improved survival rates for patients on the lower dose of 1 mg daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical profile of anastrozole. Lønning, PE., Geisler, J., Dowsett, M.[2019]

Anastrozole, a selective aromatase inhibitor, was evaluated in a phase II trial involving 53 women with recurrent müllerian cancer, showing modest toxicity and primarily resulting in stable disease rather than significant tumor shrinkage.

While 42% of patients experienced stable disease for over 90 days, the overall tumoricidal activity was minimal, indicating that anastrozole may not be effective as a primary treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of anastrozole in women with asymptomatic müllerian cancer. del Carmen, MG., Fuller, AF., Matulonis, U., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7243137/

Aromatase Inhibitors Plus Weight Loss Improves ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11245298/

Role of Aromatase Inhibitors in Managing Hypogonadism in ... A robust improvement in serum total testosterone and LH levels with a decline in oestradiol levels was documented with the use of anastrozole or letrozole over ...

3. academic.oup.com academic.oup.com/jcem/article/89/3/1174/2844209

Effects of Aromatase Inhibition in Elderly Men with Low or ... We conclude that the aromatase inhibitor anastrozole increases androgen production and normalizes serum testosterone levels in older men with mild hypogonadism.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2603924922000386

Aromatase inhibitors in male: A literature review In a study by Shoshany et al., in about 95% of males with hypoandrogenism treated with anastrozole, testosterone was significantly increased from 258.4 ± 10.8 ...

5. tau.amegroups.org tau.amegroups.org/article/view/64746/html

Efficacy of anastrozole in the treatment of hypogonadal ... Conclusions: Anastrozole improves hormonal profiles and semen parameters in hypogonadal, subfertile men with body mass index over 25 kg/m2 and may aid in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15001605/

Effects of aromatase inhibition in elderly men with low or ... These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels to the youthful normal range in older men with mild ...