Spironolactone for Hyperandrogenism in Pubertal Girls

(CBS010 Trial)

Overseen By Melissa Gilrain, BS

Age: < 18

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must be taking: Spironolactone

Must not be taking: Eplerenone

Disqualifiers: Diabetes, Virilization, Cancer, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks per treatment period

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism (HA), androgen-receptor blockade (spironolactone) alone normalizes sleep-wake luteinizing hormone (LH) pulse frequency (primary endpoint) and overall LH and follicle-stimulating hormone secretion (secondary endpoints).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking medications that might interact with spironolactone, such as eplerenone, you may need to stop those. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug spironolactone for hyperandrogenism in pubertal girls?

Research shows that spironolactone is effective in treating hirsutism (excessive hair growth) in conditions like polycystic ovary syndrome (PCOS), which is related to high levels of male hormones. This suggests it may help with hyperandrogenism (excess male hormones) in pubertal girls as well. ^{1 2 3 4 5}

Is spironolactone safe for use in humans?

Spironolactone has been used in various studies for conditions like familial male precocious puberty and hyperandrogenic disorders, showing no important adverse effects in short-term use and only mild side effects in women with hyperandrogenic conditions. ^{1 4 6 7 8}

How does the drug spironolactone differ from other treatments for hyperandrogenism in pubertal girls?

Spironolactone is unique because it acts as an antiandrogen by blocking testosterone receptors, which helps manage symptoms of hyperandrogenism like hirsutism (excessive hair growth). It is particularly useful for those who cannot use hormonal contraceptives, offering a non-hormonal option for managing these symptoms. ^{1 2 4 7 9}

Research Team

Christine M Burt Solorzano, MD

Principal Investigator

University of Virginia Center for Research in Reproduction

Eligibility Criteria

This trial is for mid to late pubertal girls aged 10-17 with hyperandrogenism, which could be high testosterone levels or excessive hair growth. They should be in good health overall and agree to avoid pregnancy using non-hormonal methods during the study.

Inclusion Criteria

I am committed to using non-hormonal birth control methods during the study.

I am a girl aged 10-17, either after my first period or in the later stages of puberty.

You have high levels of testosterone in your blood or show signs of excessive hair growth.

Exclusion Criteria

Your total testosterone level is higher than 150 ng/dl.

I have symptoms or a diagnosis of low testosterone due to pituitary or hypothalamic causes.

You are pregnant or currently breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are pretreated with spironolactone or placebo for 2 weeks before each clinical research unit admission

2 weeks per treatment period

2 admissions (in-person)

Crossover

Participants switch treatments between spironolactone and placebo for another 2 weeks before the second admission

2 weeks per treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Spironolactone

Trial Overview The trial tests if Spironolactone, a medication that blocks androgen receptors, can normalize sleep-wake luteinizing hormone pulse frequency in these girls. The study also looks at its effects on other hormones like LH and FSH compared to a placebo.

Participant Groups

Group I: Spironolactone Experimental Treatment 1 Intervention

Prior to the first or second admission (randomly determined), participants will be pretreated for 2 weeks with spironolactone (50 mg twice daily).

Group II: Placebo Placebo Group 1 Intervention

Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily).

Spironolactone is already approved in United States, European Union for the following indications:

Approved in United States as Aldactone for:

• High blood pressure
• Heart failure
• Liver scarring
• Kidney disease
• Low blood potassium
• Early puberty in boys
• Acne
• Excessive hair growth in women

Approved in European Union as Aldactone for:

• Fluid retention due to heart failure
• Liver scarring
• Kidney disease
• High blood pressure
• Low blood potassium

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+

Findings from Research

In a study of nine boys aged 3.3 to 7.7 years with familial male precocious puberty, a combination of the antiandrogen spironolactone and the estrogen synthesis inhibitor testolactone effectively normalized growth rates and bone maturation after at least six months of treatment.

The combined therapy also helped control symptoms like acne and aggressive behavior without significant adverse effects, although further research is needed to evaluate long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of familial male precocious puberty with spironolactone and testolactone. Laue, L., Kenigsberg, D., Pescovitz, OH., et al.[2013]

The combination of spironolactone and testolactone effectively manages familial male precocious puberty by maintaining plasma testosterone levels while blocking its receptor, as shown in an 18-month pilot study followed by an extended treatment of 2 to 4.2 years in eight boys.

As boys continued treatment, they experienced a rise in gonadotropin levels, leading to a diminished response to the therapy; however, adding the LHRH agonist deslorelin successfully reduced peak LH, plasma testosterone, and bone maturation rate, helping to regain control over puberty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. Laue, L., Jones, J., Barnes, KM., et al.[2018]

A review of five studies indicates that spironolactone may be an effective treatment for hirsutism in women with polycystic ovary syndrome (PCOS), showing a positive trend in outcomes.

The research highlights that while various treatment options exist for hirsutism, spironolactone has demonstrated promising results in addressing this common issue associated with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spironolactone for hirsutism in polycystic ovary syndrome. Christy, NA., Franks, AS., Cross, LB.[2013]

In a study of 34 hirsute adolescents treated with spironolactone for 8 months, 70.6% showed significant improvement in hirsutism, indicating its efficacy as a treatment.

All participants experienced a decrease in testosterone levels, suggesting that spironolactone effectively reduces androgen levels, which is likely a key mechanism in alleviating hirsutism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The treatment of hirsutism in adolescent girls with spironolactone]. Malinova, M.[2013]

In a study of 82 young women with polycystic ovary syndrome (PCOS), both spironolactone and metformin improved menstrual cycle frequency and reduced hirsutism, but spironolactone was more effective in these areas.

Spironolactone was associated with fewer adverse events compared to metformin, making it a safer option for managing symptoms of PCOS, while both medications improved insulin sensitivity and hormonal levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. Ganie, MA., Khurana, ML., Eunice, M., et al.[2013]

In a study of 13 women with anovulatory oligomenorrhea and hyperandrogenism, treatment with spironolactone led to ovulation in 85% of participants and significant reductions in hormone levels such as LH and testosterone over six menstrual cycles.

Spironolactone also improved symptoms of hirsutism in 70% of the women and restored regular menstrual cycles in 85%, with only mild side effects reported, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of ovulation with spironolactone (Aldactone) in anovulatory oligomenorrheic and hyperandrogenic women. Evron, S., Shapiro, G., Diamant, YZ.[2019]

In a study of 63 women with hyperandrogenic skin disorders due to polycystic ovary syndrome (PCOS), spironolactone was found to be an effective and safe treatment, with significant improvement reported after an average of 25.7 months of therapy.

The effects of spironolactone were long-lasting, with 38 patients maintaining improvement for an average of 33.7 months after stopping the medication, although some experienced relapse within 17.5 months, particularly those with the ovulatory PCOS phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Lasting Effects of Spironolactone after its Withdrawal in Patients with Hyperandrogenic Skin Disorders. Sabbadin, C., Beggiao, F., Keiko Vedolin, C., et al.[2023]

In a study of 100 children, spironolactone was commonly used in diuretic regimens, particularly for those with heart disease and chronic lung disease, with an average treatment duration of 16 days.

While initial use of spironolactone was associated with hyperkalemia (high potassium levels), long-term use led to hypokalemia (low potassium levels), highlighting the need for careful potassium monitoring in pediatric patients, especially those on multiple diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with spironolactone in pediatrics. Buck, ML.[2013]

Spironolactone, at a dose of 5 mg/kg daily for one week, significantly increased serum LH levels by 60% in boys with delayed puberty, indicating its potential efficacy in stimulating gonadotropin secretion.

The drug's mechanism involves blocking testosterone synthesis and competing for androgen receptors, but individual responses varied, especially in patients with Kallmann's syndrome, highlighting the need for larger doses to achieve consistent results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence. Santen, RJ., Kulin, HE., Loriaux, DL., et al.[2018]

References

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

Treatment of familial male precocious puberty with spironolactone and testolactone. [2013]

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

Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. [2018]

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

Spironolactone for hirsutism in polycystic ovary syndrome. [2013]

4. Bulgaria pubmed.ncbi.nlm.nih.gov

[The treatment of hirsutism in adolescent girls with spironolactone]. [2013]

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

Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. [2013]

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

Induction of ovulation with spironolactone (Aldactone) in anovulatory oligomenorrheic and hyperandrogenic women. [2019]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Long-Lasting Effects of Spironolactone after its Withdrawal in Patients with Hyperandrogenic Skin Disorders. [2023]

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

Clinical experience with spironolactone in pediatrics. [2013]

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

Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence. [2018]