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

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate changes in blood vessels around the heart (e.g., aorta and carotid arteries) and in the brain with the loss of female sex hormones (e.g., estrogen) during the menopause transition. The menopause transition is associated with declines in blood vessel function and increased risk for cardiovascular disease and Alzheimer's disease. Increasing evidence supports an early role for declines in blood vessel function and future development of Alzheimer's disease in aging men and women. This study will learn about the effects of changes in female sex hormones, such as estrogen, during the menopause transition on blood vessel around the heart and in the brain in women.

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 data supports the effectiveness of the drug GnRH antagonist for menopause?

GnRH antagonists have been shown to be effective in treating conditions like uterine fibroids, endometriosis, and certain cancers by directly reducing hormone levels quickly. This suggests they might also help manage menopause symptoms by controlling hormone levels. ^{1 2 3 4 5}

Is the GnRH antagonist treatment generally safe for humans?

GnRH antagonists, like Elagolix, have been studied for conditions like endometriosis and prostate cancer. They are generally considered to have a lower risk of cardiovascular issues compared to similar treatments, and they avoid some side effects like hypersensitivity reactions that older versions had. ^{6 7 8 9 10}

How does the GnRH antagonist drug work for menopause treatment?

The GnRH antagonist drug works by directly blocking the action of the hormone GnRH on the pituitary gland, leading to an immediate decrease in the hormones that stimulate the ovaries, without the initial surge seen with other treatments. This rapid action and avoidance of the initial 'flare-up' make it unique compared to other hormone therapies. ^{1 4 7 11 12}

Research Team

Lyndsey DuBose, PhD

Principal Investigator

University of Colorado Denver Anschutz Medical Campus

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. Bulgaria pubmed.ncbi.nlm.nih.gov

[Gonadotropin releasing hormone (GnRH) antagonists--a new provocation in gynecology]. [2006]

2. United States pubmed.ncbi.nlm.nih.gov

The effect of delayed initiation of gonadotropin-releasing hormone antagonist in a flexible protocol on in vitro fertilization outcome. [2013]

3. Turkey pubmed.ncbi.nlm.nih.gov

Comparison of long GnRH agonist versus GnRH antagonist protocol in poor responders. [2020]

4. Ireland pubmed.ncbi.nlm.nih.gov

Clinical application of GnRH-antagonists. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. Germany pubmed.ncbi.nlm.nih.gov

Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Overview of elagolix for the treatment of endometriosis. [2017]

8. England pubmed.ncbi.nlm.nih.gov

The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist. [2023]

10. Switzerland 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. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

GnRH-antagonists in reproductive medicine. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

A clinician's guide to the use of gonadotropin-releasing hormone analogues in women. [2015]