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

60 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Progesterone + Estradiol for treating polycystic ovary syndrome?

Research shows that treatments combining estrogen and progestin (a synthetic form of progesterone) can be effective for managing symptoms of polycystic ovary syndrome (PCOS). Studies have evaluated similar combinations, like ethinyl estradiol with progestin, which have shown efficacy in managing PCOS symptoms. ^{1 2 3 4 5}

Is the combination of progesterone and estradiol generally safe for humans?

Research on similar hormone combinations, like nomegestrol acetate with estradiol, shows they are generally well tolerated in humans, with common side effects being acne and changes in menstrual bleeding. No serious health issues like cancer or organ disease were reported in these studies. ^{6 7 8 9 10}

How does the drug Progesterone + Estradiol differ from other treatments for polycystic ovary syndrome?

Progesterone + Estradiol is unique because it combines two hormones that may help regulate menstrual cycles and improve fertility in women with polycystic ovary syndrome (PCOS), unlike other treatments that often focus on reducing symptoms like excess hair growth or acne. This combination may offer a novel approach by directly addressing hormonal imbalances associated with PCOS. ^{4 11 12 13 14}

What is the purpose of this trial?

Girls with high levels of the male hormone testosterone often develop polycystic ovary syndrome (PCOS) as adults. Women with PCOS often have irregular menstrual periods, excess facial and body hair, and weight gain. Women with PCOS also have difficulty becoming pregnant. Some, girls with high levels of male hormone will develop normal hormone levels as they grow up. Most girls continue to have high levels of male hormone as adults. In addition, girls with elevated levels of male hormones often have lower fertility rates in adulthood. In this study the investigators will aim to discover the effect of 7 days of estrogen and progesterone on GnRH pulses in girls and women with the goal of understanding how and why some girls and women have higher levels of male hormone and the causes of PCOS. If investigators understand the causes of these disorders, they may be able to better treat them and perhaps even learn how to prevent the development of PCOS.

Research Team

Chris McCartney, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. England pubmed.ncbi.nlm.nih.gov

The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Clinical efficacy and metabolic impact of two different dosages of ethinyl-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: a randomized study. [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproterone and desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome]. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of different timing of letrozole initiation on pregnancy outcome in polycystic ovary syndrome. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy. [2021]

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

Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor-progesterone derivative. [2013]

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

Profile of a new low dose combination estrogen and progestogen oral contraceptive: a review of nine clinical studies. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Acceptance and subjective well-being with a norgestimate combination pill]. [2013]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Nomegestrol acetate/estradiol: in oral contraception. [2021]

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

Role of luteal phase support on gonadotropin ovulation induction cycles in patients with polycystic ovary syndrome. [2014]

12. England pubmed.ncbi.nlm.nih.gov

Efficacy of an oral contraceptive containing drospirenone in the treatment of women with polycystic ovary syndrome. [2013]

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

Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. [2022]

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

Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome. [2013]