Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic Ovary Syndrome (PCOS), Anovulation, Elevated Testosterone
Brief summary
The purpose of this study is to determine if the combination therapy of lifestyle intervention and use of Metformin together will improve ovulation induction and hyperandrogenemia in women with polycystic ovary syndrome, by gathering data from adult and adolescent females.
Detailed description
PCOS is characterized by excess circulating androgen levels and chronic anovulation. PCOS is also characterized by insulin resistance and hyperinsulinemia. Several recent studies in a variety of non-hospital based populations have provided evidence that the incidence of hyperandrogenic chronic anovulation is in the range of 4-6% of the female population. Improvements in insulin sensitivity in women with PCOS, either through lifestyle changes or through pharmaceutical intervention, have consistently resulted in a marked improvement in the reproductive and metabolic abnormalities in PCOS. The primary objective in the adult female population is to determine that combination therapy will improve ovulatory frequency. Secondary objective is to improve circulating hyperandrogenemia and insulin sensitivity then single agent therapy. The primary objective of the adolescent population is to determine that the combination therapy will improve hyperandrogenemia. Secondary objective is to improve ovulatory frequency and insulin sensitivity than just the use of a single agent therapy.
Interventions
DRUGMetformin
Medication was initiated in a step-up fashion every five days, from one tablet per day to four (500 mg per tablet).
DRUGPlacebo
Placebo
BEHAVIORALLifestyle Intervention
A combined intervention of diet and exercise was employed with the goal of achieving an average weight loss of at least 7% of initial body weight over six months with a prescription of 150 min/week of exercise combined with a low-calorie diet.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Spontaneous intermenstrual periods of greater than or equal to 45 days or a total of 8 or less periods per year * Elevated testosterone levels * General good health * Off of current medications which may confound response to study medications
Exclusion criteria
* Pregnancy * Lactose Intolerance * Medical Contraindications * Elevated Prolactin, 17hydroxyprogesterone, or Follicle stimulating hormone blood tests * Diabetes, liver, heart, kidney or uncorrected thyroid disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Testosterone After 6 Months of Treatment | baseline and 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ovulation Rate | 6 months | Count of ovulations per subject during the treatment period. |
| Change in Insulin Sensitivity Index After 6 Months of Treatment | baseline and 6 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin Metformin 2000mg/d (2 500mg tablets taken twice a day) initiated in a step-up fashion | 55 |
| Placebo Placebo (2 tablets twice a day) initiated in a step-up fashion | 59 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Lost to Follow-up | 15 | 19 |
| Overall Study | Pregnancy | 0 | 4 |
| Overall Study | Withdrawal by Subject | 12 | 20 |
Baseline characteristics
| Characteristic | Placebo | Metformin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 55 Participants | 114 Participants |
| Age, Continuous | 28.8 years STANDARD_DEVIATION 4.6 | 29 years STANDARD_DEVIATION 4.5 | 28.9 years STANDARD_DEVIATION 4.6 |
| Region of Enrollment United States | 59 participants | 55 participants | 114 participants |
| Sex: Female, Male Female | 59 Participants | 55 Participants | 114 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 55 | 33 / 59 |
| serious Total, serious adverse events | 0 / 55 | 0 / 59 |
Outcome results
Primary
Change in Testosterone After 6 Months of Treatment
Time frame: baseline and 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Metformin | Change in Testosterone After 6 Months of Treatment | -2.1 ng/dL |
| Placebo | Change in Testosterone After 6 Months of Treatment | -6.4 ng/dL |
p-value: 0.5495% CI: [-9.9, 18.4]Mixed Models Analysis
Secondary
Change in Insulin Sensitivity Index After 6 Months of Treatment
Time frame: baseline and 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Metformin | Change in Insulin Sensitivity Index After 6 Months of Treatment | 1.9 index |
| Placebo | Change in Insulin Sensitivity Index After 6 Months of Treatment | -2.7 index |
p-value: 0.0595% CI: [0.1, 9]Mixed Models Analysis
Secondary
Ovulation Rate
Count of ovulations per subject during the treatment period.
Time frame: 6 months
Population: A total of 76 patients with daily urine collections.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metformin | Ovulation Rate | 2 ovulations | 4 Participants |
| Metformin | Ovulation Rate | 4 ovulations | 4 Participants |
| Metformin | Ovulation Rate | 1 ovulation | 6 Participants |
| Metformin | Ovulation Rate | 5 ovulations | 1 Participants |
| Metformin | Ovulation Rate | 3 ovulations | 7 Participants |
| Metformin | Ovulation Rate | 6+ ovulations | 5 Participants |
| Metformin | Ovulation Rate | 0 ovulations | 10 Participants |
| Placebo | Ovulation Rate | 6+ ovulations | 3 Participants |
| Placebo | Ovulation Rate | 0 ovulations | 19 Participants |
| Placebo | Ovulation Rate | 1 ovulation | 5 Participants |
| Placebo | Ovulation Rate | 2 ovulations | 7 Participants |
| Placebo | Ovulation Rate | 3 ovulations | 3 Participants |
| Placebo | Ovulation Rate | 4 ovulations | 2 Participants |
| Placebo | Ovulation Rate | 5 ovulations | 0 Participants |
Comparison: This statistical analysis models the probability of ovulation.p-value: 0.0795% CI: [0.9, 6.6]Zero-altered negative binomial model
Comparison: This statistical analysis models the count of ovulations provided a woman actually ovulated.p-value: 0.5195% CI: [0.7, 1.9]Zero-altered negative binomial model