Combination Therapy with Metformin and Inositol Improves Menstrual Regularity and Hirsutism in PCOS: Study

PCOS is a complex syndrome characterized by dysfunction in the hormonal axis, associated with insulin resistance and disrupted metabolism. Though these abnormalities can lead to many symptoms such as irregular menstruation, acne, hirsutism, etc, it is not what defines or commonly determines the syndrome. The metabolic features of PCOS are treated with metformin, an insulin sensitizer. Of late, natural compounds, such as inositols, which have mediators for insulin signaling, are considered a potential therapeutic avenue.

A search of all relevant trials in the PubMed, Embase, and Cochrane databases was undertaken to search for randomized controlled trials that compare combination therapy of metformin plus inositol with metformin monotherapy in women diagnosed with PCOS. A total of six RCTs were included in the analysis, involving a total of 388 participants. The follow-up period in the reviewed studies ranged between 3 to 6 months. Calculations of RRs and MDs were done using a random-effect model with 95% CIs. A p-value of < 0.05 was required for statistical significance.

The meta-analysis yields several major findings that reflect the advantages of combination treatment compared with metformin monotherapy:

• In the combination therapy, the risk ratio was significantly higher than 1, RR: 1.56 (95% CI 1.01 to 2.41, p = 0.04), meaning that women treated with both drugs were 56% more likely to have regular cycles compared to women treated with metformin.

• Using the modified Ferriman-Gallwey score, there was a significant reduction in hirsutism on combination therapy. The MD is −0.97 (95% CI −1.53 to −0.40, p < 0.01), and it implies that with combination therapy, excess body hair levels are lower compared with monotherapy.

• Combination treatment brought about highly significant reduction of the LHR/FSHR ratio; SD, −0.13 (95% CI −0.24 to −0.03, p = 0.01), which suggests that there is a better hormonal balance in women with PCOS.

• Improvement of acne was not significantly different between the two groups, (p = 0.58).

• The BMI changes were not statistically significant (p = 0.13).

• It was found that there is no significant change in the fasting blood glucose level (p = 0.07).

• The HOMA-IR showed no statistically significant changes (p = 0.25).

In this meta-analysis results showed that combination therapy with inositol and metformin was regularity of menstrual cycles, reduced hirsutism, and decreased LH/FSH ratio compared to metformin monotherapy. These results suggest a possible beneficial effect on reproductive health, but lack of significant improvement in the metabolic markers indicates the need for further study to fully assess the effects of inositol in PCOS management. For now, the combination of metformin and inositol seems to have an advantage in countering some of the hormonal and reproductive challenges of PCOS.

Reference:

Kelly, F. A., de Oliveira Macena Lôbo, A., Cardoso, J. H. C. O., & de Moraes, F. C. A. (2024). Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Endocrine. https://doi.org/10.1007/s12020-024-04052-3