Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

Children's Mercy Hospital Kansas City

Status and phase

Completed

Phase 3

Phase 2

Conditions

PCOS

Treatments

Drug: Metformin and Spironolactone

Study type

Interventional

Funder types

Other

Identifiers

NCT03981861

16010020

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

Female

Ages

13 to 21 years old

Volunteers

No Healthy Volunteers

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)