Spironolactone for Hyperandrogenism in Pubertal Girls (CBS010 Trial)
Recruiting in Palo Alto (17 mi)
Age: < 18
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Virginia
Approved in 2 jurisdictions
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).
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.
12459Is 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.
23579Will 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.
24568Eligibility 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.
I am committed to using non-hormonal birth control during the study.
I am a girl aged 10-17, either after my first period or in mid to late puberty.
Exclusion Criteria
I am unable to understand or sign the consent form.
I weigh less than 21.5 kg.
I am younger than 10 or older than 17 years old.
My obesity is due to a hormonal disorder or genetic condition.
I am not eligible for this trial because I am male.
My kidney function is reduced with a GFR under 60.
I have signs of increased male traits.
I might have Cushing's syndrome, adrenal insufficiency, or acromegaly based on my symptoms or doctor's exam.
I have diabetes or my blood sugar or A1c levels are high.
I cannot take spironolactone due to severe adverse reactions.
I have a serious heart or lung condition.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: SpironolactoneExperimental Treatment1 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: PlaceboPlacebo Group1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Center for Research in Reproduction, University of VirginiaCharlottesville, VA
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Who is running the clinical trial?
University of VirginiaLead Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Collaborator
References
Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence. [2018]Spironolactone (Aldactone) acts as an antiandrogen by blocking testosterone synthesis and competing with testosterone for the androgen receptor. These properties of the mineralcorticoid antagonist were used in an attempt to interrupt the gonadal-pituitary-hypothalamic negative feedback axis and thereby stimulate LH and FSH in 7 boys with delayed puberty. Following administration of aldactone (5 mg/kg) daily for one week, there was a significant (P less than .01) mean increase in serum LH of 60%. In all 7 boys an absolute rise in LH was observed, but these changes were statistically significant in only 5 individuals. While mean FSH levels increased by 60% in this group of boys, the individual responses were variable. No rise in gonadotropin levels occurred in 2 patients with Kallmann's syndrome, who also received 5 mg/kg of spironolactone daily for 1 week. Large doses of the drug appeared necessary to stimulate gonadotropin secretion since a dose of 3 mg/kg per day did not cause LH or FSH increments in 2 additional patients with delayed puberty. Progesterone and 17alpha-hydeoxyprogesterone levels increased to a greater extent than LH and FSH in response to spironolactone, reflecting either adrenal or testicular enzyme inhibition. Spiornolactone is the first drug shown to be capable of stimulating gonadotropin secretion by interrupting negative feedback inhibition in boys with delayed puberty.
Treatment of familial male precocious puberty with spironolactone and testolactone. [2013]Because the pubertal growth spurt in boys appears to be mediated by both androgens and estrogens, we hypothesized that blockade of both androgen action and estrogen synthesis would normalize the growth of boys with familial male precocious puberty. To test this hypothesis, we studied nine boys (age range, 3.3 to 7.7 years) during treatment with an antiandrogen (spironolactone) or an inhibitor of androgen-to-estrogen conversion (testolactone), followed by treatment with both agents. After six months of observation without treatment, the first four boys received spironolactone for six months, followed by spironolactone and testolactone. The next five boys received testolactone for six months, followed by spironolactone and testolactone. Neither spironolactone nor testolactone, given alone, was satisfactory as a treatment for this condition. However, a combination of spironolactone and testolactone, given for at least six months, restored both the growth rate and the rate of bone maturation to normal prepubertal levels and controlled acne, spontaneous erections, and aggressive behavior. The combined therapy was associated with a significantly lower growth rate than testolactone alone (P less than 0.05) and a significantly lower rate of bone maturation than spironolactone alone (P less than 0.05). No important adverse effects were observed during combined treatment. Six of the nine boys continued to receive the combined therapy for an additional 12 months and maintained normal prepubertal rates of growth and bone maturation. The mean predicted height (+/- SEM) increased progressively during the combined treatment although the difference between the pretreatment and post-treatment predictions was not significant (169.5 +/- 2.8 at the end of treatment vs. 166.2 +/- 4.5 cm before treatment; P = 0.29). We conclude that blockade of both androgen action and estrogen synthesis with the combination of spironolactone and testolactone is an effective short-term treatment for familial male precocious puberty. Further study will be required, however, to assess the long-term outcome in boys who receive this treatment.
Induction of ovulation with spironolactone (Aldactone) in anovulatory oligomenorrheic and hyperandrogenic women. [2019]Thirteen anovulatory oligomenorrheic, hyperandrogenic, and normoprolactinemic women were treated with spironolactone (aldactone) throughout six consecutive menstrual cycles in a dosage of 100 to 150 mg/day. During this treatment a significant decrease in serum luteinizing hormone (LH), testosterone, prolactin, and 17-ketosteroid values were observed that were accompanied by ovulation in 11 women (85%), according to basal body temperature (BBT) and progesterone values. In addition, improvement of hirsutism was observed in 9 (70%) and restoration of regular cycles in 11 (85%) of the patients. The side effects observed were mild and did not lead to interruption of the treatment. Our data suggest that the antiandrogenic properties of spironolactone render it a suitable agent in the treatment of anovulatory, oligomenorrheic, and hyperandrogenic women.
Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. [2018]Combined antiandrogen (spironolactone) and aromatase inhibitor (testolactone) are effective for the short term treatment of familial male precocious puberty. During this therapy, plasma testosterone levels remain in the adult range, since spironolactone blocks the testosterone receptor without significantly affecting plasma testosterone levels. After our initial 18-month pilot study, we continued to treat eight boys with the combined therapy for 2.0-4.2 yr. During this time all boys exhibited a pubertal rise in gonadotropin secretion and a diminishing response to treatment, which was manifested by the recurrence of clinical features of puberty and an increase in the bone maturation rate (P
[The treatment of hirsutism in adolescent girls with spironolactone]. [2013]The purpose of this study was to determine the antiandrogenic properties of spironolactone on hirsute adolescents.
Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. [2013]We compared the efficacy of spironolactone (50 mg/d) with metformin (1000 mg/d) after random allocation in 82 adolescent and young women with polycystic ovary syndrome (PCOS) on body mass index (BMI), waist-to-hip ratio, blood pressure, menstrual cyclicity, hirsutism, hormonal levels, glycemia, and insulin sensitivity at baseline and at the 3rd and 6th months of treatment. Sixty-nine women who completed the follow-up had a mean age of 22.6 +/- 5.0 yr and mean BMI of 26.8 +/- 4.0 kg/m2. The number of menstrual cycles in the spironolactone and metformin groups increased from 6.6 +/- 2.1 and 5.7 +/- 2.3 at baseline to 9.0 +/- 1.9 and 7.4 +/- 2.6 at 3rd month and to 10.2 +/- 1.9 and 9.1 +/- 2.0/ year at the 6th month (P = 0.0037), respectively. The hirsutism score decreased from 12.9 +/- 3.2 and 12.5 +/- 4.9 at baseline to 10.1 +/- 3.1 and 11.4 +/- 4.1 at the 3rd month and to 8.7 +/- 1.9 and 10.0 +/- 3.3 at the 6th month, respectively. Both groups showed improvement in glucose tolerance and insulin sensitivity, although the metformin effect was significant in the latter. Serum LH/FSH and testosterone decreased in both groups. BMI, waist-to-hip ratio, and blood pressure did not change with either drug. We conclude that both drugs are effective in the management of PCOS. Spironolactone appears better than metformin in the treatment of hirsutism, menstrual cycle frequency, and hormonal derangements and is associated with fewer adverse events.
Clinical experience with spironolactone in pediatrics. [2013]In 2003, the Food and Drug Administration placed spironolactone on its list of drugs needing pediatric studies.
Spironolactone for hirsutism in polycystic ovary syndrome. [2013]To evaluate the level of evidence for treatment of hirsutism associated with polycystic ovary syndrome (PCOS) with spironolactone.
Long-Lasting Effects of Spironolactone after its Withdrawal in Patients with Hyperandrogenic Skin Disorders. [2023]Hyperandrogenic skin disorders, such as hirsutism, acne and alopecia, affect approximately 10-20% of women of reproductive age, reducing quality of life and causing psychological impairment. Spironolactone is a commonly used antiandrogen, especially in women who are not sexually active or have contraindications to hormonal contraceptives. The aim of this study was to evaluate the effects of spironolactone, especially after its withdrawal, in patients with hyperandrogenic skin disorders.