Nestler, J. E., Jakubowicz, D. J., Reamer, P., Gunn, R. D., & Allan, G. (1999). Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. The New England Journal of Medicine, 340(17), 1314-1320. https://doi.org/10.1056/NEJM199904293401703
Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314-1320. doi:10.1056/NEJM199904293401703
Nestler, John E., et al. "Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome." The New England Journal of Medicine, vol. 340, no. 17, 1999, pp. 1314-1320.
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Hospital Clínico Universitario de Caracas00vpxhq27
Virginia Commonwealth University Medical Center057xmsr27
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RRM Academy Synopsis
More women with PCOS ovulated on D-chiro-inositol than on placebo
A 1999 trial gave 44 obese women with polycystic ovary syndrome (PCOS, now also called PMOS) D-chiro-inositol or a placebo. About 9 out of 10 women on the drug ovulated, versus about 3 out of 10 on placebo.
Key Findings
Nineteen of 22 women given D-chiro-inositol ovulated (86 percent), compared with 6 of 22 given placebo (27 percent) (P<0.001). Ovulation was presumed from weekly blood progesterone tests.
Free testosterone fell in the D-chiro-inositol group, and the change differed from placebo (P=0.006). Sex hormone-binding globulin rose, and that change also differed from placebo (P=0.003).
The insulin response to a glucose drink fell in the D-chiro-inositol group (P=0.007), but the fall did not differ significantly from the placebo change (P=0.07).
Diastolic blood pressure fell 4 mm Hg and systolic fell 4 mm Hg, compared with placebo (P<0.001 and P=0.05). Triglycerides fell more than in the placebo group (P=0.002).
Body-mass index did not change in either group, and the authors noted no side effects in either group.
Interpretation
The trial was a small, randomized, double-blind (neither women nor staff knew the assignment), placebo-controlled study run in one hospital in Caracas. It enrolled obese women aged 18 to 40 with PCOS and followed them six to eight weeks. Ovulation was presumed from progesterone blood tests. Women were advised to avoid intercourse or use a barrier method, and the trial did not measure pregnancy. The authors did not assess the cause of the insulin change directly, and it did not differ significantly from placebo. The drug maker co-funded the study, and one author consulted for that company.
RRM Context
Restorative reproductive medicine treats missing ovulation as a sign of a cause. Insulin resistance is one known driver in PCOS, and this trial targeted it. The authors compare the hormone changes with earlier drugs that improve insulin action. Evaluation in restorative care includes both partners, since male factor plays a part in many couples.
Our editorial summary of this paper, not the article's abstract.
Abstract
Background
Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity.
Methods
We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of D-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation.
Results
In the 22 women given D-chiro-inositol, the mean (+/-SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417+/-11,572 to 5158+/-6714 microU per milliliter per minute (81+/-69 to 31+/-40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1+/-0.8 to 0.5+/-0.5 ng per deciliter (38+/-7 to 17+/-3 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women's diastolic and systolic blood pressure decreased by 4 mm Hg (P<0.001 and P=0.05, respectively, for the comparisons with the changes in the placebo group), and their plasma triglyceride concentrations decreased from 184+/-88 to 110+/-61 mg per deciliter (2.1+/-0.2 to 1.2+/-0.1 mmol per liter) (P=0.002 for the comparison with the change in the placebo group). None of these variables changed appreciably in the placebo group. Nineteen of the 22 women who received D-chiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P<0.001).
Conclusions
D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.
