GnRH Antagonist for Menopause

Overseen By Kerrie Moreau, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must not be taking: Menopausal therapy, Hormonal contraceptives

Disqualifiers: Hypertension, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how changes in female sex hormones, such as estrogen, during menopause affect blood vessels near the heart and brain. The goal is to determine if these changes might increase risks for heart disease and Alzheimer’s. The treatment under investigation is a GnRH antagonist, a drug that temporarily reduces hormone levels. Ideal participants are healthy women who are premenopausal, early perimenopausal, or postmenopausal, experiencing natural menopause and not using hormone therapies. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, aiming to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that might influence cardiovascular function or cerebral blood flow, as well as menopausal therapy or hormonal contraceptives within the previous 3 months. You also need to stop using vitamin/supplements or chronic anti-inflammatory medications 1 month before the vascular visit.

What is the safety track record for this treatment?

Research has shown that degarelix, a type of medication, is approved for treating advanced prostate cancer, indicating its safety is well-understood. Studies indicate that common side effects usually result from lower estrogen levels due to hormone changes. These side effects can include symptoms like hot flashes or mood swings, but they are generally manageable. No serious side effects have been widely reported in these studies. Overall, people generally tolerate it well. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike other treatments for menopause that often involve hormone replacement therapy, the GnRH antagonist degarelix acetate offers a unique approach. This treatment works by blocking the action of the gonadotropin-releasing hormone, which is a different mechanism compared to traditional hormone therapies. It's administered as a single subcutaneous injection, providing a potentially more convenient and targeted option for managing menopause symptoms. Researchers are particularly excited about this treatment because it may offer an alternative for those who can't take standard hormone therapies due to health risks or personal preferences.

What is the effectiveness track record for GnRH antagonist in treating menopause?

Research shows that GnRH antagonists, which participants in this trial will receive, can quickly lower sex hormone levels like estrogen in women. This reduction occurs within hours to a few days and may help manage menopause symptoms. Studies have also found that these drugs can reduce pain from conditions like endometriosis, indicating they effectively change hormone levels to improve quality of life. However, one study found that this treatment might decrease bone strength, so its impact on bones should be monitored. Overall, GnRH antagonists have effectively managed hormone-related conditions in women. ^{6 7 8 9 10}

Who Is on the Research Team?

Lyndsey DuBose, PhD

Principal Investigator

University of Colorado Denver Anschutz Medical Campus

Are You a Good Fit for This Trial?

This trial is for healthy premenopausal and postmenopausal women experiencing the menopause transition, with regular menstrual cycles or natural menopause. Participants should not have high blood pressure, be on certain medications, pregnant, or have a BMI over 39. They must not smoke or live with a smoker.

Inclusion Criteria

My bone density test shows I have osteopenia or osteoporosis.

I am not allergic to Degarelix or its components.

We will make a major effort to ensure that the women enrolled in this study come from all races and ethnicities and a wide range of socioeconomic and educational levels

Exclusion Criteria

Smoking or living with a smoker within the past 12 months

I have not used hormonal therapies or contraceptives in the last 3 months and do not plan to start during the study.

I do not have any major illnesses like diabetes, cancer (other than melanoma), liver or heart disease that could affect the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a GnRH antagonist (degarelix acetate, 80 mg) as a subcutaneous injection to evaluate changes in blood vessels during menopause transition

12 weeks

Follow-up

Participants are monitored for changes in blood vessel function and cerebral blood flow after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GnRH antagonist

Trial Overview The study investigates how the loss of female sex hormones like estrogen during menopause affects heart and brain blood vessels. It aims to understand if these changes increase risks for cardiovascular disease and Alzheimer's. A GnRH antagonist will be used to study these effects.

How Is the Trial Designed?

Group I: Premenopausal Group: GnRH antagonist Experimental Treatment 1 Intervention

Gonadotropin releasing hormone (GnRH) antagonist is degarelix acetate, 80 mg, delivered once as a subcutaneous injection.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

In a study of 45,059 men with prostate cancer receiving androgen deprivation therapy, the risk of major adverse cardiovascular events (MACE) was found to be significantly higher for those treated with GnRH antagonists compared to LHRH agonists, with a hazard ratio of 1.62.

Additionally, the risk of all-cause mortality was also greater for patients on GnRH antagonists versus LHRH agonists, indicating that LHRH agonists may be a safer option in terms of cardiovascular health following ADT initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist. Crawford, ED., Hafron, JM., Debruyne, F., et al.[2023]

Men with advanced nonmetastatic prostate cancer on gonadotropin-releasing hormone (GnRH) agonists experienced a significantly higher increase in comorbidity rates compared to those on antiandrogens (AAs), with a 5.6% greater excess rate of change per year after starting treatment.

The risk of developing new comorbidities was 32% higher for men on GnRH agonists compared to those on AA monotherapy, indicating that GnRH agonists may pose a greater risk of adverse health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer. Beckmann, K., Garmo, H., Adolfsson, J., et al.[2019]

GnRH antagonists, such as cetrorelix and ganirelix, provide a promising alternative to traditional GnRH agonists for preventing premature LH surges during ovarian stimulation, with comparable clinical outcomes and reduced treatment times.

These antagonists are associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) and are preferred by patients over agonist treatments, indicating their potential to become the preferred choice in assisted reproductive techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The place of gonadotrophin-releasing hormone antagonists in reproductive medicine. Howles, CM.[2019]

In a study of 442 IVF patients using a flexible GnRH antagonist protocol, 323 patients started antagonist administration on or before stimulation day 6 (S6), while 119 patients started later, with no significant difference in implantation rates (30.4% vs. 33.7%) or ongoing pregnancy rates (41.2% vs. 47.9%).

Patients who started the antagonist later had higher body mass index and required longer stimulation with more gonadotropins, but their reproductive outcomes remained comparable to those who started earlier, indicating that timing of antagonist administration may not compromise fertility outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of delayed initiation of gonadotropin-releasing hormone antagonist in a flexible protocol on in vitro fertilization outcome. Tannus, S., Weissman, A., Boaz, M., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8645162/

Depot Pure GnRH Antagonist for Long-term Treatment of ... Accordingly, administration of a pure GnRH antagonist has been reported to rapidly (within 6-72 hours) suppress ovarian steroidogenesis in postmenopausal women ...

2. rbmojournal.com rbmojournal.com/article/S1472-6483(24)00510-8/fulltext

systematic review and meta-analysis assessing GnRH ... In the Elaris EM-I trial, 20.9% of women treated with elagolix 200 mg twice daily experienced a 5% or greater decrease in BMD at 6 months, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02005887

TRial on the Endocrine Activity of Neoadjuvant Degarelix The result is a fast and profound reduction in LH, FSH and in turn, testosterone suppression. Its activity in suppressing the ovaries of premenopausal women ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12239828/

Oral Gonadotropin-Releasing Hormone Antagonists in the ... Research has demonstrated that oral GnRH antagonists effectively alleviate endometriosis-related pain while enhancing patients' quality of life.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0015028208015033

Long-term effects of GnRH agonist, GnRH antagonist, and ... Our data demonstrate that long-term GnRH antagonist treatment increases proapoptotic bax gene expression, and that estrogen plus progesterone treatment ...

6. go.drugbank.com go.drugbank.com/drugs/DB06699

Degarelix: Uses, Interactions, Mechanism of Action Degarelix is a GnRH receptor antagonist used in the management of advanced prostate cancer ... View sample adverse effects data in our new Data Library!

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8940613/

Current approaches to overcome the side effects of GnRH ... The majority of side effects that occur in women during the use of GnRH agonists are related to sex hormone deficiency and include the symptoms of low estrogen ...

8. es.aetna.com es.aetna.com/cpb/medical/data/500_599/0501.html

Gonadotropin-Releasing Hormone Analogs and Antagonists Retreatment cannot be recommended for the management of endometriosis since safety data for retreatment are not available. ... The GnRH antagonist degarelix ...

9. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1358278/full

Effectiveness and safety of GnRH antagonist originator and ... This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide and generic Ferpront.

10. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/degarelix

Degarelix - an overview Degarelix (1) is a synthetic, long-acting peptide derivative of GnRH, which acts as an antagonist and is approved for the treatment of advanced prostate cancer.