Inositol Supplementation to Treat PCOS (INSUPP-PCOS)

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.

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.