Clinical trial · Interventional
Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls (JCM025)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Many, but not all, girls with high levels of the male hormone testosterone go on to develop polycystic ovary syndrome (PCOS) as adults. Women with PCOS often have irregular menstrual periods, excess facial and body hair, and weight gain. PCOS is also a leading cause of difficulty becoming pregnant. The investigators do not understand why some girls with high hormones develop PCOS and others do not. In a previous study by our group, some girls with high levels of male hormones had abnormalities in the secretion of another hormone, called luteinizing hormone (LH), that are often seen in women with PCOS. However, another group had normal LH secretion. The girls with the abnormal LH secretion had higher levels of another hormone, called insulin, than the girls with normal LH secretion. The investigators will test whether metformin, an insulin-sensitizing agent, changes the effects of high male hormone levels in adolescent girls, specifically by looking at their LH secretion response following metformin treatment.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Hyperandrogenism | — | UNRESOLVED | — |
| Polycystic Ovary Syndrome | — | UNRESOLVED | — |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| estrace | Drug | — | UNRESOLVED |
| Metformin | Drug | Metformin | ALIAS |
| Progesterone | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Metformin, progesterone , estrace
- description
- 12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)
- interventionNames
- Drug: Metformin
- Drug: Progesterone
- Drug: estrace
Primary outcomes (1)
- measure
- Change in Progesterone Sensitivity Index Before and After Metformin Treatment.
- timeFrame
- 12 weeks following start of metformin treatment
- description
- The progesterone (P4) sensitivity index is defined as the percent change in 11-hour LH pulse frequency before and after P4 and estradiol administration for 7 days, divided by the day 7 mean serum P4 concentration. We compared the P4 sensitivity index after metformin administration to the baseline P4 sensitivity index, using Wilcoxon signed-rank test.
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 10 Years
- Maximum age
- 17 Years
Show eligibility criteria text
Inclusion Criteria: * Girls ages 10 to 17 * Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage) * Creatinine clearance \> 90 ml/min as calculated by the Cockcroft-Gault equation * Hemoglobin \> 12 mg/dL or Hematocrit \> 36% * Normal screening labs (with exception of the expected hormonal abnormalities inherent in hyperandrogenemia) * Sexually active subjects must agree to abstain or use double barrier contraception during the study * Subjects must agree not to take any other medications during the course of the study without approval by the study investigators. Exclusion Criteria: * Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia) * Creatinine clearance less than 90 ml/min as calculated by Cockcroft-Gault equation * Hemoglobin \<12 mg/dL or hematocrit \< 36% * Abnormal liver function tests, including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin, Albumin, and Alkaline Phosphatase * Weight \< 34 kg * History of renal dysfunction, liver dysfunction, congestive heart failure, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer * Pregnant or breast feeding * On medications known to affect the reproductive axis within 3 months of the study (including oral contraceptive pills, metformin, and spironolactone) * Are currently participating in another study or have been in one in the last 30 days. * Subjects using restricted medication (see restrictions below) are excluded unless the subject's primary care provider approves stopping the medication.
References
Publications (1)
- DERIVEDLundgren JA, Kim SH, Burt Solorzano CM, McCartney CR, Marshall JC. Progesterone Suppression of Luteinizing Hormone Pulse Frequency in Adolescent Girls With Hyperandrogenism: Effects of Metformin. J Clin Endocrinol Metab. 2018 Jan 1;103(1):263-270. doi: 10.1210/jc.2017-02068. PMID 29095983