An interventional study of Metformin and Progesterone in Polycystic Ovary Syndrome and Hyperandrogenism, sponsored by University of Virginia. Completed at 1 site in United States. Open to female participants aged 10 Years to 17 Years. Per ClinicalTrials.gov, last updated 2021-01-08.
Sponsored by University of Virginia · Not applicable, Interventional, and Basic science
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.
A better understanding of the factors that make adolescent girls more or less susceptible to the adverse neuroendocrine effects of elevated androgens will hopefully lead to improved prevention and treatment strategies for PCOS. In this study, we propose to explore the role of hyperinsulinemia on neuroendocrine function in hyperandrogenic adolescent girls by assessing the effect of the insulin sensitizer Metformin on hypothalamic progesterone sensitivity. Other differences between the progesterone sensitive and progesterone insensitive subgroups, including racial and ethnic differences between the two populations and a trend towards older gynecologic age in the progesterone insensitive population, are being pursued through other ongoing studies (IRB-HSR# 8588 and 12160).
Exclusion Criteria:
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)
Drug: Metformin · Drug: Progesterone · Drug: estrace
500-2000 mg PO BID (X12 weeks)
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)
oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2
Also known as: Estrogen
Change in Progesterone Sensitivity Index Before and After Metformin Treatment.
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.
Time frame: 12 weeks following start of metformin treatment
| Milestone | Metformin, Progesterone , Estrace |
|---|---|
| Started | 25 |
| Completed | 12 |
| Not completed | 13 |
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.
| % change in LH pulses/day 7 P4 level | Metformin, Progesterone , Estrace |
|---|---|
| Before Metformin | -4.12 ± 2.39 |
| After Metformin | -4.29 ± 7.66 |
Collected over From start of study procedures until 30 days post study drug.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin, Progesterone , Estrace | 0/25 (0%) | 0/25 (0%) | 12/25 (48%) |
| Event | Metformin, Progesterone , Estrace |
|---|---|
| UTIInfections and infestations | 3/25 |
| nauseaGeneral disorders | 2/25 |
| diarrheaGastrointestinal disorders | 2/25 |
| Vision switched from near to farsightedEye disorders | 1/25 |
| SVTCardiac disorders | 1/25 |
| InfectionInfections and infestations | 1/25 |
| headacheGeneral disorders | 1/25 |
| faintingGeneral disorders | 1/25 |
| Acute GastroenteritisGastrointestinal disorders | 1/25 |
| heartburnGeneral disorders | 1/25 |
25 subjects enrolled and 12 completed the study. Only 10 subjects were included in the formal analysis.
| Age, Categorical(Participants) | Metformin, Progesterone , Estrace |
|---|---|
| <=18 years | 10 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age, Continuous(years) | Metformin, Progesterone , Estrace |
|---|---|
| Mean | 15.3 ± 1.2 |
| Sex: Female, Male(Participants) | Metformin, Progesterone , Estrace |
|---|---|
| Female | 10 |
| Male | 0 |
| Race (NIH/OMB)(Participants) | Metformin, Progesterone , Estrace |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 8 |
| More than one race | 2 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Metformin, Progesterone , Estrace |
|---|---|
| United States | 10 |
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University of Virginia