Testosterone Therapy for Pain in Postmenopausal Women

Overseen By Julia Crosby

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Opioid analgesics

Must not be taking: Estrogen, Testosterone, Spironolactone, others

Disqualifiers: Breast cancer, Endometrial cancer, Diabetes, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether testosterone therapy can reduce pain and improve quality of life for postmenopausal women with chronic back pain who already use opioids. Researchers aim to determine if adding Testosterone Cypionate affects pain perception, pain tolerance, and overall well-being compared to a placebo. Participants will receive either the testosterone treatment or a placebo through weekly injections. Women who have experienced chronic back pain and have used opioids for at least six months might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have used testosterone, spironolactone, finasteride, or systemic ketoconazole in the past 3 months.

Is there any evidence suggesting that testosterone cypionate is likely to be safe for humans?

Research has shown that testosterone therapy is generally safe for women after menopause. Studies have found that using testosterone in regular doses is mostly safe over several years. Some women might experience side effects such as increased hair growth and acne, which are the most commonly reported issues. Overall, testosterone therapy has been linked to a lower risk of breast cancer, making it a promising option for many women. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Testosterone Cypionate is unique because it introduces a hormone-based approach to managing pain in postmenopausal women, which differs from the common use of NSAIDs or opioids. While most current treatments focus on directly alleviating pain, testosterone therapy may address underlying hormonal imbalances that contribute to pain after menopause. Researchers are excited about this treatment because it offers a potential new pathway for pain relief that could reduce reliance on conventional pain medications, which often come with significant side effects or risk of dependency.

What evidence suggests that testosterone therapy might be an effective treatment for pain in postmenopausal women?

In this trial, participants will receive either testosterone therapy or a placebo. Research has shown that testosterone therapy can help manage pain and improve sexual function in postmenopausal women. One study found that women who received testosterone reported a 43% reduction in pain, compared to a 35% reduction in those who received a placebo. However, this difference was not statistically significant, indicating it might not be due to the treatment. Testosterone has also been found to help with low sex drive, which is common in postmenopausal women. While more research is needed specifically on pain, these early findings suggest that testosterone might improve how women feel and tolerate pain. ^{5 6 7 8 9}

Who Is on the Research Team?

Shehzad Basaria, M.D.

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for postmenopausal women over 60 with chronic back pain who have been on opioids for at least 6 months and show low testosterone levels. They must have a normal mammogram, appropriate endometrial thickness, and be able to consent. Women with a history of certain cancers, severe obesity, recent heart issues or strokes, specific blood conditions or kidney dysfunction are not eligible.

Inclusion Criteria

I have long-term back pain not caused by cancer.

Use of opioid analgesics for at least 6 months

Serum total testosterone <8.7 ng/dL and/or free testosterone <0.47 pg/mL

Exclusion Criteria

Baseline hematocrit >48%

I have not had a heart attack, stroke, or any heart surgery in the last 3 months.

Serum creatinine >2.5 mg/dL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly intramuscular administration of testosterone or placebo for 3 months

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Testosterone Cypionate

Trial Overview

The TRAPP Trial is testing if testosterone replacement (using Testosterone Cypionate) can better improve pain perception, tolerance, sexual function, physical ability and life quality in these women compared to a placebo.

How Is the Trial Designed?

Group I: Testosterone Experimental Treatment 1 Intervention

Weekly intramuscular administration at a dose of 3 mg

Group II: Placebo Placebo Group 1 Intervention

Weekly intramuscular administration of placebo

Testosterone Cypionate is already approved in United States for the following indications:

Approved in United States as Depo-Testosterone for:

• Primary hypogonadism
• Hypogonadotropic hypogonadism
• Delayed puberty

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Testosterone therapy is increasingly considered for postmenopausal women, but there is limited data supporting its use in premenopausal women, despite the important roles androgens play in their health, including mood, libido, and bone mass.

Testosterone deficiency in young women may be underdiagnosed due to nonspecific symptoms and inaccurate measurement techniques, and while testosterone therapy can have benefits, long-term safety and efficacy studies are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone therapy in premenopausal women. Kalantaridou, SN., Calis, KA.[2013]

Testosterone plays a crucial role in various aspects of health for women, including sexual function, bone density, and mood, with deficiency potentially arising from conditions like menopause, oophorectomy, or adrenal disease.

Current research is focusing on developing a consensus for diagnosing female androgen deficiency syndrome (FADS) and exploring treatment options, including a new testosterone transdermal patch that may offer benefits over traditional estrogen replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone deficiency in women: etiologies, diagnosis, and emerging treatments. Mazer, NA.[2013]

Testosterone undecanoate, when administered at 40 mg daily for 4 days to 10 postmenopausal women, showed rapid absorption with peak serum levels of testosterone and related hormones occurring 2-4 hours after the first dose.

The treatment resulted in significant increases in testosterone, dihydrotestosterone, and estradiol levels, while follicle-stimulating and luteinizing hormone levels remained unchanged, suggesting that testosterone undecanoate could be a viable option for androgen therapy in postmenopausal women, though careful monitoring is necessary due to individual variations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of testosterone undecanoate in postmenopausal women: effects on androgens, estradiol, and gonadotrophins. Flöter, A., Carlström, K., von Schoultz, B., et al.[2019]

Testosterone replacement therapy can significantly improve symptoms like fatigue and low libido in postmenopausal women experiencing androgen deficiency, enhancing their overall quality of life.

The exact mechanism of how testosterone exerts its therapeutic effects—whether directly or through conversion to estrogen—is still unclear, but the use of testosterone in hormone replacement regimens for women is likely to increase with new formulations becoming available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen replacement in women: a commentary. Davis, S.[2013]

In a pilot study involving 64 women, self-administration of subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) showed a 12-month continuation rate of 12%, which was not significantly different from the 22% rate in the control group using intramuscular DMPA (DMPA-IM).

Women reported similar satisfaction levels with both self-administered DMPA-SC and clinician-administered DMPA-IM, indicating that self-injection is a feasible and effective option for contraception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of home self-administration of subcutaneous depo-medroxyprogesterone acetate for contraception. Cameron, ST., Glasier, A., Johnstone, A.[2022]

Testosterone therapy is becoming more common in hormone replacement therapy (HRT) for postmenopausal women, but there are limited approved androgenic preparations specifically for women.

Concerns remain about the long-term effects of testosterone therapy on women's health, particularly regarding breast, endometrial, and cardiovascular health, highlighting the need for further research in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of postmenopausal testosterone therapy. Maclaran, K., Panay, N.[2016]

Testosterone replacement therapy aims to maintain physiological testosterone levels, with parenteral testosterone undecanoate showing significant improvement by providing stable levels for up to 12 weeks, compared to traditional esters that require administration every 2-3 weeks.

Transdermal testosterone gel offers a flexible dosing option and produces stable serum testosterone profiles, making it particularly recommended for elderly males, while allowing for immediate discontinuation in case of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in testosterone replacement therapy. Gooren, L.[2019]

Depot medroxyprogesterone acetate (DMPA) and medroxyprogesterone acetate/estradiol cypionate (MPA/E(2)C) are highly effective and safe injectable contraceptive options for women, with DMPA notably reducing the risk of endometrial cancer by 80%.

Both contraceptive methods may cause minor side effects, such as menstrual irregularities and amenorrhea with DMPA, highlighting the importance of patient counseling for successful long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current options for injectable contraception in the United States. Kaunitz, AM.[2013]

Short-term testosterone therapy, especially when combined with traditional hormone treatments, has been shown to improve sexual function in postmenopausal women, particularly those with hypoactive sexual desire disorder.

While testosterone therapy shows promise, it may negatively affect lipid profiles, particularly with oral methyltestosterone, and more research is needed to understand its long-term health risks and the specific populations that would benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen and menopause. Somboonporn, W.[2013]

Testosterone plays a crucial role in women's health, particularly in addressing loss of sexual desire, yet there are no approved formulations for this purpose despite its widespread off-label use.

Transdermal testosterone therapy has not shown adverse cardiovascular effects in women, and clinical trials suggest it may enhance cognitive performance and improve musculoskeletal health in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone in women--the clinical significance. Davis, SR., Wahlin-Jacobsen, S.[2022]

Testosterone undecanoate offers a more stable and effective treatment for androgen deficiency compared to traditional injectable testosterone, with injections spaced 12 weeks apart after an initial loading phase, maintaining plasma testosterone levels within the normal range.

This new formulation has an excellent safety profile, showing no adverse effects on blood parameters, lipid profiles, or prostate health, while effectively reversing symptoms of hypogonadism in bone, muscle, and sexual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone depot injection in male hypogonadism: a critical appraisal. Yassin, AA., Haffejee, M.[2021]

Testosterone therapy during menopause offers benefits beyond sexual health, as it can stimulate estrogen production in tissues that express aromatase, enhancing overall well-being.

The use of tibolone, which increases free testosterone levels by inhibiting sex hormone-binding globulin (SHBG), can be an effective strategy for androgen replacement therapy in perimenopausal women experiencing symptoms of androgen deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement therapy in the climacteric: benefits beyond sexuality. Maia, H., Casoy, J., Valente, J.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9674516/

The clinical management of testosterone replacement therapy ...

TRT is an effective treatment option for postmenopausal people with HSDD. There is still limited data on the effectiveness in premenopausal people with HSDD.

2.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT04895306/testosterone-replacement-to-alleviate-pain-in-postmenopausal-women-trapp-trial

Testosterone Replacement to Alleviate Pain in ...

The aim of this trial is to evaluate whether testosterone replacement results in greater improvement in pain perception, pain tolerance, sexual function, ...

3.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/trial/listing/542516

Testosterone Replacement to Alleviate Pain in ...

The aim of this trial is to evaluate whether testosterone replacement results in greater improvement in pain perception, pain tolerance, sexual function, ...

4.

withpower.com

withpower.com/trial/phase-3-7-2021-dea47?condition=Low+Testosterone&overallStatus=Recruiting&hasNoPlacebo=false

Testosterone Therapy for Pain in Postmenopausal Women

The aim of this trial is to evaluate whether testosterone replacement results in greater improvement in pain perception, pain tolerance, sexual function, ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7644633/

A randomized, double-blind, placebo-controlled trial of ...

Pain reduction at 3 months was observed in all three arms of the study: 35% with placebo, 43% with testosterone 40 mg (p=0.06), and 70% with ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9331845/

A Personal Prospective on Testosterone Therapy in Women ...

A recent study, The Dayton Study, noted that testosterone was associated with a 39% lower incidence of breast cancer than predicted by ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0015028207002816

Safety of testosterone treatment in postmenopausal women

Except for hirsutism and acne, the therapeutic administration of T in physiologic doses is safe for up to several years.

8.

fertstert.org

fertstert.org/article/S0015-0282(07)00281-6/fulltext

Safety of testosterone treatment in postmenopausal women

Except for hirsutism and acne, the therapeutic administration of T in physiologic doses is safe for up to several years.

9.

aetna.com

aetna.com/cpb/medical/data/1000_1099/1014.html

Testosterone Cypionate Injections - Medical Clinical Policy ...

These researchers studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, ...