Progesterone + Estradiol for Polycystic Ovary Syndrome

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Virginia

Must not be taking: Hormonal medications

Disqualifiers: Congenital adrenal hyperplasia, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a short course of estrogen (Estrace) and progesterone affects hormone levels in girls with high male hormone levels who are at risk for developing polycystic ovary syndrome (PCOS). PCOS can cause issues such as irregular periods, excess hair growth, and difficulty getting pregnant. By understanding these hormone changes, researchers aim to find better treatments or even ways to prevent PCOS. Girls aged 8 to 18 with high testosterone or signs of excess male hormones might be suitable for this study. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new insights and preventive strategies for PCOS.

Will I have to stop taking my current medications?

Yes, if you are on hormonal medications or medications that affect the reproductive system, you must stop taking them at least 3 months before joining the study.

What prior data suggests that this treatment is safe for girls and women with PCOS?

Research has shown that using a combination of estrogen and progesterone is generally safe, though some risks exist. Studies have found that estrogen, as in birth control pills, can increase the risk of blood clots, particularly in veins. This risk depends on the dose and type of hormones used.

When combined, estrogen and progesterone may cause side effects like nausea or headaches in some women. These effects are typically mild and temporary.

Overall, while most people tolerate the treatment well, awareness of these potential risks is important, and discussing them with a healthcare provider is advised. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Progesterone and Estrace for treating Polycystic Ovary Syndrome (PCOS) because these hormones offer a potentially more natural approach to managing the condition. Unlike traditional treatments like birth control pills or metformin, which primarily aim to regulate menstrual cycles or insulin levels, this combination targets hormonal balance more directly. By using micronized progesterone and estradiol (the active form of Estrace), this treatment mimics the body's natural hormonal fluctuations, which could lead to improved symptom management with possibly fewer side effects. This approach offers a promising alternative for those seeking treatments that align more closely with the body's natural processes.

What evidence suggests that this trial's treatments could be effective for PCOS?

Research has shown that using estrogen and progesterone can help manage polycystic ovary syndrome (PCOS) by regulating periods and reducing high levels of male hormones. In this trial, participants will receive a combination of Estrace (estrogen) and progesterone. Studies have found that treatments with low doses of estrogen and various types of progesterone can restore normal menstrual cycles in women with PCOS. These treatments can also improve symptoms like excess facial and body hair caused by high testosterone levels. Additionally, progesterone levels can predict pregnancy outcomes for women with PCOS. This evidence suggests that using estrogen and progesterone together could effectively address some main issues of PCOS. ^{6 7 8 9 10}

Who Is on the Research Team?

Chris McCartney, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for girls aged 8 to 18 with high male hormone levels, specifically testosterone >0.4 ng/mL or signs of excess hair growth. They must have normal lab results except for those related to high male hormones and weigh over 31 kg. Girls can't join if they've had certain cancers, are on hormonal treatments, pregnant/breastfeeding, smoke cigarettes, or have specific medical conditions.

Inclusion Criteria

I am a girl aged between 8 and 18.

Your lab test results are normal, except for the expected hormonal imbalances associated with high levels of male hormones.

You have high testosterone levels or excessive hair growth.

Exclusion Criteria

I had surgery that needed bed rest in the last 30 days.

My family has a history of blood clotting disorders not related to surgery or cancer.

I weigh less than 31 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive estrogen and progesterone to assess the sensitivity of the GnRH pulse generator

1 week

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estrace
• Progesterone

Trial Overview The study tests how a week-long treatment with estrogen (estrace) and progesterone affects the GnRH pulses in young females with elevated male hormones. The goal is to understand the development of PCOS and potential treatments by monitoring changes in hormone patterns.

How Is the Trial Designed?

Group I: estrogen, progesterone Experimental Treatment 2 Interventions

Estrace, 0.5-1 mg once a day Micronized progesterone powder (Spectrum Chemical Manufacturing Corporation, Irving, CA), Three times a day at 0700, 1500, and 2300 hr

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8538639/

Cyclic Progesterone Therapy in Androgenic Polycystic Ovary ... This pilot study's purpose was to document 6-month experience changes in a woman with PCOS taking cyclic progesterone therapy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7924872/

Estrogen Receptors in Polycystic Ovary Syndrome - PMC This article focuses on the recent progress in PCOS caused by the abnormal expression of estrogen and ERs in the ovaries and uterus.

3. e-enm.org e-enm.org/journal/view.php?number=2155

An Update on Contraception in Polycystic Ovary Syndrome Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits ...

4. rbej.biomedcentral.com rbej.biomedcentral.com/articles/10.1186/s12958-021-00862-6

Exploration of the value of progesterone and progesterone ... The progesterone level is significantly better than the P/E2 ratio in predicting the pregnancy outcome of PCOS patients, especially in ultralong ...

5. impactfactor.org impactfactor.org/PDF/IJCPR/17/IJCPR,Vol17,Issue3,Article263.pdf

Comparison of the Outcomes of Polycystic Ovary Syndrome ... Conclusion: This study indicates that COCs are most effective for menstrual regularity, anti-androgens provide the best results for reducing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5399491/

Adverse Effects of the Common Treatments for Polycystic ... AA use has been associated with hepatic toxicity that could be fatal (17). The risk and nature of these side effects must be considered when choosing therapies.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8090477/

An Update on Contraception in Polycystic Ovary Syndrome COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events ...

8. academic.oup.com academic.oup.com/jcem/article/100/3/794/2838953

Contraception in Women With Polycystic Ovary Syndrome Currently available evidence indicates an increased relative risk of venous thrombosis associated with OCs varying among different formulations. Arterial ...

9. uptodate.com uptodate.com/contents/combined-estrogen-progestin-oral-contraceptives-patient-selection-counseling-and-use

Combined estrogen-progestin oral contraceptives The data regarding safety of ... polycystic ovary syndrome or nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

10. emedicine.medscape.com emedicine.medscape.com/article/256806-medication

Polycystic Ovarian Syndrome Medication Ethinyl estradiol combined with drospirenone (Yasmin) has a progestin that acts as an antiandrogen and thus may add antiandrogenic effects. Withdrawal bleeding ...