Progesterone for Androgen Syndrome during Puberty

(CRM003 Trial)

Overseen By Melissa Gilrain

Age: < 18

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must not be taking: Oral contraceptives, Metformin, Glucocorticoids, Stimulants

Disqualifiers: Males, Pregnancy, Diabetes, Cancer, others

Compensation: Varies

Number of Visits: 2

Duration: 18 hours per admission, with at least 2 months between admissions

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether progesterone, a natural hormone, can help manage hormone levels in girls undergoing puberty. It examines how progesterone affects luteinizing hormone (LH) in girls with and without signs of excessive male hormones, such as extra hair growth, during puberty. Girls in mid- to late-stage puberty, with or without signs of excessive male hormones, and in generally good health, may qualify for this study. Participants will receive either micronized progesterone suspension or a placebo to observe their body's response. As an Early Phase 1 trial, this research aims to understand how progesterone functions in people, offering participants the chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure at least 2 months before the screening visit and 3 months before starting the study medications. This includes oral contraceptives, progestins, metformin, systemic glucocorticoids, some antipsychotics, and stimulants like methylphenidate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that micronized progesterone is generally safe. Studies have found it to be well-tolerated by most people, meaning it usually doesn't cause problems. Importantly, it does not increase the risk of breast cancer.

One study discovered that the body quickly absorbs micronized progesterone, and it works well compared to other hormone treatments. While absorption may vary among individuals, it typically doesn't cause serious side effects.

Overall, micronized progesterone has been used safely in various situations, supporting its safety in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Micronized progesterone suspension is unique because it introduces a natural hormone, progesterone, as a potential treatment for Androgen Syndrome during puberty. Unlike standard treatments that may focus on managing symptoms with synthetic hormones or other medications, this approach uses progesterone in a micronized form, which may enhance absorption and effectiveness. Researchers are excited about this treatment because it could offer a more natural and possibly more effective way to balance hormone levels and manage the symptoms of Androgen Syndrome during a critical developmental period.

What evidence suggests that micronized progesterone might be an effective treatment for androgen syndrome during puberty?

This trial will compare micronized progesterone suspension with a placebo. Studies have shown that micronized progesterone can be beneficial in several ways. Specifically, it improves satisfaction with breast development, which is important for individuals undergoing gender affirmation therapy. Additionally, it is safe for most people. However, it does not significantly alter male hormone levels when taken orally. While it may not lower certain male hormones, it offers other benefits and is generally well-tolerated. ^{2 6 7 8 9}

Who Is on the Research Team?

Christine M Burt Solorzano, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for mid- to late pubertal girls with or without hyperandrogenism (HA), which includes conditions like excessive body hair. Participants must be generally healthy, not pregnant, and willing to avoid pregnancy. Girls with HA should have higher than normal testosterone levels or visible signs of hirsutism. Those without HA need normal testosterone levels and no hirsutism.

Inclusion Criteria

I am generally healthy, though I may be overweight or have hormone imbalances.

Girls with high levels of testosterone in their blood or clear signs of excessive hair growth will not be included.

I, or my guardian, can and will agree to participate in the study.

Exclusion Criteria

I am unable to understand or sign the consent form.

Your body mass index (BMI) is in the lowest 5% for your age, which means you are underweight.

You are pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two 18-hour Clinical Research Unit (CRU) admissions with either progesterone or placebo administered at specific times, with blood sampling every 10 minutes to measure LH pulse frequency.

18 hours per admission, with at least 2 months between admissions

2 CRU admissions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Micronized progesterone suspension
• Placebo

Trial Overview

The study tests if progesterone can reduce waking luteinizing hormone (LH) frequency more during wakefulness than sleep in girls without HA, and if its effect on LH is less in girls with HA compared to those without. It involves comparing a micronized progesterone suspension against a placebo.

How Is the Trial Designed?

Group I: Micronized progesterone suspension Experimental Treatment 1 Intervention

Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone.

Group II: Placebo Placebo Group 1 Intervention

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11294403/

Diagnostic and therapeutic use of oral micronized ...

They were a more effective treatment than per os administrated natural progesterone which presented poor absorption and rapid metabolic decay.

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1544319123002522

Effects of progesterone on gender affirmation outcomes as ...

The progesterone group had statistically significant improvements in satisfaction with breast development at 6 months (53.8% vs. 19.6%; P = 0.004) and 9 months ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9686158/

Hypogonadism in adolescent girls: treatment and long-term ...

The available data so far indicates that transdermal 17β-estradiol and micronized progesterone have the most favorable outcomes and safety profile. However ...

4.

fertstert.org

fertstert.org/article/S0015-0282(02)03119-9/fulltext

Effect of oral micronized progesterone on androgen levels ...

Our results indicated that total T, free T, SHBG, DHEAS, A4, or 17-OHP did not change significantly with OMP administration (Table 1). A higher 17-OHP level was ...

5.

japha.org

japha.org/article/S1544-3191(23)00252-2/fulltext

Effects of progesterone on gender affirmation outcomes as ...

The addition of progesterone to standard feminizing GAHT was associated with greater satisfaction with breast development and improved patient mental health ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11594581/

The Potential Health Risks and Benefits of Progesterone in the ...

The currently available data do not support the implementation of progesterone in the hormonal regimen of MTF patients for the purpose of improving mental state ...

7.

researchgate.net

researchgate.net/publication/5919868_Progesterone_Review_of_Safety_for_Clinical_Studies

Progesterone: Review of Safety for Clinical Studies

Therefore, micronized natural progesterone appears to be a safe and effective alternative to synthetic and natural progesterone formulations for ...

8.

en.wikipedia.org

en.wikipedia.org/wiki/Pharmacokinetics_of_progesterone

Pharmacokinetics of progesterone

Oral micronized progesterone suspended in oil is rapidly and almost completely absorbed from the intestines. There is wide interindividual variability in the ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04534881

Effect of Progesterone on Testosterone Concentrations and ...

Purpose. The purpose of this research is study the effect of progesterone therapy on testosterone levels in transwomen who are currently on gender affirming ...