Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

Phase 2

Completed

Conditions: PCOS

Interventions: Drug: Metformin and Spironolactone

Registration Number: NCT03981861

Lead Sponsor: Children's Mercy Hospital Kansas City

Brief Summary: To exam in the effect of a combination of low dose Metformin and Spironolactone on functional brain MRI, menstrual regulation and metabolism in adolescents with PCOS.

Detailed Description: Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in adolescent females and also one of the most complex. Patients experience an exaggerated ovarian/adrenal androgen production in response to physiologic and supra-physiologic elevations in insulin. The hormonal dysregulation is not only associated with acne, hirsutism, and menstrual irregularity, but also with perpetuated insulin resistance, central adiposity, and clinical depression.

In the proposed study, we aim to treat a hormonally and metabolically well-defined group of adolescent girls with PCOS with a combination of two pharmacological agents: metformin (insulin sensitizer) and spironolactone (anti-androgen) for 6 months. Although hyperandrogenism is a fundamental component of PCOS and responsible for the perpetuation of insulin resistance, adiposity and anovulation, there are few pediatric studies that have examined the benefits of treating both insulin resistance and hyperandrogenism simultaneously. Preliminary studies in adults, however, suggest synergistic effect of both spironolactone and metformin (spiro-met) with near normalization of the metabolic and ovulatory dysfunction. Therefore, we hypothesize that spiro-met will improve adolescent metabolism, body composition, ovarian morphology/function. We anticipate that our study will generate key pilot data for further randomized, double blind placebo controlled trials using both agents.

We also plan to examine functional brain MRI before and after the spiro-met intervention. This will allow us to inspect the effects of the hyperinsulinemic/androgenic hormonal milieu in PCOS on structural and functional brain MRI. We hypothesis, that the hormonal environment in PCOS affects centers of appetite and mood.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 12

Inclusion Criteria

Generally healthy
Meeting Androgen Excess Society (AES) diagnostic criteria of PCOS: Menstrual Dysfunction or PCO ovaries on ultrasound AND clinical or biochemical hyperandrogenism
Normal liver and kidney function
No chronic illnesses except for stable, treated hypothyroidism

Exclusion Criteria

Use of metformin and/or spironolactone within the last 6 months
Currently on either oral hormonal contraception or other forms of hormonal contraception such as Depo-Provera, NuvaRing
Current or past pregnancy
Currently sexually active
Psychiatric disorder based on self/parental report
Type 2 diabetes (blood glucose > 200mg/dl on OGTT)
Anemia (Hct < 35)
Impaired kidney function (Baseline creatinine > 1.0 mg)
Abnormal liver transaminases > 2 x the upper limit of normal range
Potassium elevated outside the reference range (in non-hemolyzed blood sample)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Overall Study	Metformin and Spironolactone	Treatment with Metformin and Spironolactone

Primary Outcome Measures

Name	Time	Method
Oral Glucose Tolerance Test	Change Measures: Baseline & 6 Months	Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.
Total Testosterone	Change Measures: Baseline & 6 Months	Total Testosterone measured in ng/dL
Free Testosterone	Change Measures: Baseline & 6 Months	Free Testosterone measured in ng/dL
Dehydroepiandrosterone Sulfate (DHEAS)	Change Measures: Baseline & 6 Months	DHEAS measured in mcg/dL
Body Mass Index (BMI)	Change Measures: Baseline & 6 Months	Body Mass Index measured in kg/m2