Myoinositol With Metformin vs Metformin Monotherapy in PCOS

In This Article

Abstract and Introduction

Abstract

Objective: Insulin resistance and hyperinsulinemia plays an important role in pathogenesis of polycystic ovary syndrome (PCOS). Metformin, Myoinositol and D-chiro-inositol acts as insulin sensitizers and exerts a beneficial effects in PCOS. The objective is to compare the effect of metformin monotherapy versus a combination of metformin with Myoinositol and D-chiro-inositol in PCOS.

Design: This study is a randomized controlled trial conducted over a period of 6 months. All overweight and obese women with PCOS with the age group between 18 and 35 were included and randomized into two groups, 27 in the metformin monotherapy arm and 26 in the myoinositol combination arm.

Patients and Measurements: The variables assessed were duration of menstrual cycle, anthropometric parameters, modified Ferriman Gallwey score, global acne score, Fasting insulin, HOMA-IR, fasting lipid profile, serum testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, anti-Mullerian hormone, and pelvic ultrasound to assess ovarian volume, PCOS Questionnaire score. Changes in the parameters from baseline at the end of 6 months of treatment were assessed and compared between the groups.

Results: Menstrual cycle regularity improved in both groups with significantly greater improvement in the group receiving myoinositol-based therapy (p < .001). Pregnancy rate was equal in both the arms. There was a significant improvement in PCOSQ score in myoinositol-based therapy group (p < .001). However, there was no statistically significant difference in other hormonal, metabolic parameters between two groups in spite of symptomatic benefits.

Conclusions: The addition of myoinositol to metformin exerts additional benefits in improving menstrual cycle regularity, and quality of life in women with PCOS.

Introduction

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age group of women.^[1,2] It is characterized by menstrual irregularities with oligo-anovulation, clinical and/or biochemical evidence of hyperandrogenism and polycystic ovarian morphology on imaging. Insulin resistance and hyperinsulinemia plays an important role in pathogenesis of PCOS^[3–5] and insulin sensitizers may improve the long-term outcome.^[1] Metformin is an insulin sensitizer ameliorates the chronic inflammatory state of PCOS; improve ovulation, metabolic parameters and infertility.^[1]

Myoinositol (MI) and D-chiro-inositol (DCI) act as second messengers for insulin signalling and exerts a beneficial effect in PCOS as an insulin sensitizers.^[3] Ovarian MI:DCI ratio drops to 0.2:1 in women with PCOS and restoring the levels into 40:1 may improve the ovarian function,^[6] which can be achieved by a combination of oral MI- and DCI-based therapy.^[6] Inositol is currently considered as experimental therapy in PCOS.^[1] Due to the different mechanisms of action in addition to the ovary-specific effects of MI, metformin and MI-based therapy may have a synergistic effect. Moreover, the dose of metformin requirement for the beneficial effect can be reduced when used in combination with MI.

There are very limited studies globally comparing MI and metformin-based therapies with equivocal results.^[7–10] In addition there are no clear consensuses and guidelines regarding the use of MI in PCOS, however in off-label, MI-based therapies are being increasingly used in clinical practice in women with PCOS.^[1] The drug is quite expensive as compared with metformin and whether it provides an additional benefit is not clearly known. There are only two randomized controlled trials in literature which studied the benefit of adding MI to metformin of which, only one studied anti-Mullerian hormone (AMH).^[7–10] The present well-designed randomized controlled trial is the first such study from the South Indian population which compare the effect of metformin monotherapy versus a combination of metformin with MI + DCI, in clinical, hormonal and metabolic parameters of reproductive age obese/overweight women with PCOS.

Table 1. Baseline characteristics.
Variables	Metformin monotherapy group (Mean ± SD)	Metformin + Myoinositol with D-chiro-inositol group (Mean ± SD)	p Value
Clinical variables
Age (years)	24.35 ± 5.1	24.61 ± 5.5	.406
Weight (kg)	77 ± 13.8	79.67 ± 12.9	.345
BMI (kg/m²)	31.52 ± 4.4	33.6 ± 4.0	.744
Waist circumference (cm)	102.48 ± 9.5	109.1 ± 9.9	.703
Modified Ferriman Gallwey score (mFG)	4.24 ± 1.8	3.57 ± 1.1	.86
Global acne score (GAS)	8.9 ± 4.8	7.24 ± 4.2	.19
Metabolic variables
Fasting plasma glucose (mmol/L)	5.54 ± 0.98	5.53 ± 0.98	.371
2 h postprandial glucose(mmol/L)	7.68 ± 1.58	8.44 ± 2.15	.26
Fasting insulin (pmol/L)	149.10 ± 112.5	132.64 ± 80.56	.36
HOMA-IR	5.2 ± 2.68	5.2 ± 4.73	.78
Hormonal variables
LH (mIU/mL)	15.24 ± 11.33	12.48 ± 8.29	.055
FSH (mIU/mL)	6.83 ± 3.24	9.92 ± 15.14	.145
LH:FSH ratio	2.21 ± 1.17	2.57 ± 3.61	.315
Total testosterone (nmol/L)	2.15 ± 2.23	2.05 ± 1.28	.668
SHBG (nmol/L)	22.19 ± 12.57	22.89 ± 9.14	.869
FAI	13.40 ± 13.15	15.45 ± 23.82	.801
AMH (pmo/L)	41.21 ± 31.29	37.57 ± 24.21	.339
Ovarian volumes by ultrasound
Right ovary (mL)	15.67 ± 6.26	13.79 ± 5.64	.665
Left ovary (mL)	15.37 ± 5.23	13.62 ± 5.55	.64

Abbreviations: AMH, anti-Mullerian hormone; BMI, body mass index; FAI, free androgen index; FSH, follicle stimulating hormone; LH, luteinizing hormone; SHBG, sex hormone binding globulin.

Table 2. Comparison of clinical, metabolic and biochemical outcome measures between the two groups at 6 months.
Variables	Metformin monotherapy	Metformin + Myoinositol with D-chiro-inositol	p Value
Weight (kg)	73.14 ± 13.57	77.90 ± 13.46	.16
BMI	29.70 ± 4.52	32.66 ± 3.96	.237
Waist circumference (cm)	97.38 ± 10.37	103.67 ± 10.15	.87
mFG score	3.5 ± 1.12	2.62 ± 1.20	.945
Global acne score (GAS)	4.90 ± 2.14	4.81 ± 1.94	.068
PCOSQ score	88.1 ± 15.9	108.1 ± 12.2	<.001
Fasting insulin (pmol/L)	93.68 ± 55.35	90.97 ± 44.51	.33
HOMA-IR	3.19 ± 1.46	2.95 ± 1.91	.163
LH	8.40	12.07 ± 8	.13
LH:FSH ratio	0.48	1.78 ± 0.66	.067
Total testosterone (nmol/L)	0.71	1.52 ± 0.87	.85
SHBG (nmol/L)	26.14 ± 12.44	31.03 ± 22.86	.87
FAI	6.95	6.09 ± 4.17	.606
AMH (pmol/L)	14.5	36.86 (18.57–47.92)	.39
Right ovarian volume	11.45 ± 4.68	10.71 ± 3.42	.504
Left ovarian volume	10.91 ± 4.39	9.73 ± 3.59	.99

Abbreviations: AMH, anti-Mullerian hormone; BMI, body mass index; FAI, free androgen index; FSH, follicle stimulating hormone; LH, luteinizing hormone; SHBG, sex hormone binding globulin.

Table 3. Comparison of change in PCOSQ before and after 6 months treatment in the two groups.
	MF	MI + MF
Before treatment	34.8 ± 7.9	36.3 ± 8.3
After 6 months of treatment	88.1 ± 15.9	108.1 ± 12.2
Mean difference	−15.45	−63.13
Wilcoxon signed-rank test	p < .001	p < .001
Mann–Whitney (6 m b/w groups)	p < .001