Polycystic Ovary Syndrome, Anovulation, Hyperandrogenism, Insulin Resistance, Glucose Intolerance, Metabolic Complication
Conditions
Keywords
Polycystic Ovary Syndrome, Anovulation, Hyperandrogenism, Insulin Resistance, Glucose Intolerance, Metabolic Complication
Brief summary
To determine if Inositol, a dietary supplement, will improve ovarian and adrenal androgen excess in women with Polycystic Ovarian Syndrome(PCOS).
Detailed description
This trial will test prospectively the effects of inositol supplementation in a dose ranging double blind randomized controlled trial, according to CONSORT guidelines. This will be a four armed study of three doses of inositol vs. placebo over a three month period with the reduction in hyperandrogenism (based on serum testosterone levels) as the primary outcome and key secondary outcomes of the change in sex hormone binding globulin(SHBG) and the related free androgen index, fasting insulin levels and area under the curve glucose levels from an oral glucose challenge test (OGTT). The hypothesis is that women with PCOS who receive inositol supplementation will have a dose related reduction in hyperandrogenism. Further, we propose that the primary mechanism of inositol will be a significant improvement in hyperandrogenism (both ovarian and adrenal) vs. placebo, as documented by a lower free androgen index \[decreased total testosterone and increased sex hormone blinding globulin (SHBG)\], lower sebum measures and lower antral follicle counts of the ovary and anti-Mullerian hormone, all of which will correlate with the decrease in hyperandrogenism.
Interventions
OTHERPlacebo
Placebo
DRUGInositol
1gm/bid, 2gm/bid or 3gm/bid of Inositol powder
Sponsors
Milton S. Hershey Medical Center
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Placebo Group; Active Treatment with Inositol 1gm/bid; Active Treatment with Inositol 2gm/bid; Active Treatment with Inositol 3gm/ bid
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Women with chronic anovulation or oligomenorrhea defined as spontaneous intermenstrual periods of greater than or equal to 45 days or a total of less than or equal to 8 menses per year. * Women with Hyperandrogenism defined as a total testosterone greater than 50 ng/dL or a free androgen index greater than 10. * Women with Polycystic Ovaries on Ultrasound defined as either 12 or more follicles measuring 2-9 mm in diameter or increased ovarian volume greater than 10 cm.
Exclusion criteria
* Women with Hyperprolactinemia defined as 2 prolactin levels at least one week apart greater than 30 ng/mL. * Women with known 21-hydroxylase deficiency or other enzyme deficiency leading to the congenital adrenal hyperplasia. * Women with elevated FSH levels greater than 10 mIU/mL. * Women with uncorrected thyroid disease as per ASRM guidelines for nonpregnant subjects (TSH less than 0.45 mIU/mL or greater than 4.5 MIU/mL). * Women with a suspected adrenal or ovarian tumor secreting androgens * Women with Cushing's syndrome * Women on confounding medications which affect ovarian function including metformin, hormonal contraceptives or other medications for type 2 diabetes * Women with medical conditions that are contraindications to OTC inositol or previous allergic reactions to the supplement or to the placebo maltodextrin or inulin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Testosterone | 3 months (baseline, 1 month and 3 month visits) | Total testosterone levels measured at baseline, 1 month, and 3 month visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SHBG | 3 months (baseline, 1 month and 3 month visits) | Sex hormone-binding globulin (SHBG) levels measured at baseline, 1 month, and 3 month visits. |
| Free Androgen Index (FAI) | 3 months (baseline, 1 month and 3 month visits) | Free Androgen Index calculated at baseline, 1 month, and 3 month visits. FAI is calculated as (testosterone/SHBG)\*100 (after converting testosterone to the same units as SHBG) |
| Area Under the Curve (AUC) of Glucose | 3 months (baseline and 3 month visits) | AUC of a 2-hour 75g glucose tolerance test, which measures glucose at 0, 30, 60, 90, and 120 minutes. AUC was calculated at baseline and 3 month visit. |
| Fasting Insulin | 3 months (baseline and 3 month visits) | Fasting insulin levels measured at baseline and 3 month visit. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRichard S. Legro, M.D.
Penn State College of Medicine, Hershey Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.8 years STANDARD_DEVIATION 5.9 |
| BMI status <30 kg/m2 | 8 Participants |
| BMI status >=30 kg/m2 | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 | 0 / 24 | 0 / 25 |
| other Total, other adverse events | 16 / 26 | 18 / 24 | 14 / 24 | 13 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 | 0 / 24 | 0 / 25 |
Outcome results
None listed