Table 1. List of studies focused on the treatment of hyperhomocysteinemia in PCOS women.

MI: myoinositol; Hcy: homocysteine; Hhcy: hyperhomocysteinemia; IR: insulin resistance; NIR: noninsulin resistance; EE+CA: ethinyl estradiol + cyproterone acetate; hsCRP: high sensitivity C- reactive protein; PCOS, polycystic ovarian syndrome

No.	Author name	Year of publication	Total sample size	Objective and type of study	Results	Conclusion of the study
1.	Randeva et al. [36]	2002	21 young obese PCOS women (12- exercisers, 9-nonexercisers)	Effect of six-month exercise program on total plasma Hcy levels in young overweight or obese PCOS women	They observed a statistically significant decrease in plasma Hcy levels(p<0.001) in the exercise group compared to baseline.	The study concluded that regular exercise lowers plasma Hcy levels significantly in young obese or overweight PCOS women
2.	Kilicdag et al. [37]	2005	(60 PCOS women) Group 1-20 Group 2-20 Group 3-20	A randomized trial done to assess the effects of administration of B group Vitamins and folic acid on serum Hcy levels in metformin taking PCOS women.	21.17% and 8.33% reduction in Hcy levels were observed in women supplemented with B group vitamins or folic acid+ metformin, respectively. A 26.5% increase in Hcy level was observed in women taking only metformin in three months.	B group vitamins or folic acid supplementation counteracted the metformin's Hcy elevation.
3.	Gul et al. [38]	2008	30 PCOS women	A prospective study evaluated the effect of oral contraceptive ethinyl estradiol-cyproterone acetate (EE-CA) on serum Hcy level in PCOS women.	EE-CA therapy for three months showed a statistically significant reduction in Hcy levels(p=0.01).	The study proposed that further studies are required to know the clinical benefit of this (EE-CA) therapy even though the decrease in Hcy level was statistically significant.
4.	Kazerooni et al. [39]	2008	70 Hhcy PCOS women (32-IR, 38-NIR)	A prospective clinical trial was done to investigate folic acid's effect in Hhcy PCOS women with IR and NIR after three-month therapy.	After treatment, serum Hcy levels were significantly decreased in both groups. (p<0.001-IR, p<0.001- NIR)	It was concluded that after folic acid therapy for three months, serum Hcy levels in Hhcy PCOS women significantly reduced with more reduction in NIR PCOS women.
5.	Kaya et al. [40]	2009	52 PCOS women Group 1- 26 Group 2- 26 52 controls (age & BMI matched)	A prospective randomized study performed to test the hypothesis Hhcy in PCOS women improved with statins.	Twelve weeks of treatment with atorvastatin (group 1) & simvastatin (group 2) significantly decreased Hcy levels(p<0.01) in PCOS women with more decrease observed in the atorvastatin group.	The study proposed that statin therapy helps in the reduction of serum Hcy levels in PCOS women.
6.	Makedos et al. [41]	2010	83 PCOS women (divided into five groups for five different regimes)	A prospective matched study done to assess the effects of five different hormonal regimes on serum Hcy and serum hsCRP levels in PCOS women.	All five treatment regimens 1. Conjugated estrogens+ cyproterone acetate, 2. 17β-estradiol + cyproterone acetate, 3. Ethinyl estradiol+ cyproterone acetate (high dose), 4. Ethinyl estradiol+ cyproterone acetate (low dose), 5. Ethinyl estradiol+ desogetrel, demonstrated significant reduction of Hcy levels(p< 0.001) when measured after four, seven, 12 months	Even though all five regimens favored the reduction of Hcy levels, it concluded that 17β-estradiol + cyproterone acetate regime had the most favorable effect in PCOS women in terms of both Hcy and hsCRP levels reduction.
7.	Bahmani et al. [42]	2014	69 PCOS women (18-40 years age) (Divided into three equal groups) Group 1- folate 1 mg/day Group 2- folate 5 mg/day, Group 3-placebo	A randomized, double-blinded placebo-controlled clinical trial conducted to assess the effects of folate therapy for eight weeks on inflammatory factors and biomarkers of oxidative stress in PCOS women.	The study resulted in a statistically significant decrease in Hcy levels in women treated with 5mg/day folate (p<0.05) compared with other treatment groups.	Therefore, 5mg/day folate Supplementation had favorable effects on inflammatory and oxidative stress biomarkers in PCOS women.
8.	Salehpour et al. [43]	2016	50 PCOS women	This pilot study was done to evaluate the effects of myoinositol (MI) on the cardiovascular and metabolic profile of PCOS women over 30 years of age.	After three months of therapy with MI 2 g + 200 μg of folic acid, a statistically significant reduction of serum Hcy levels(p<0.008) was observed along with significant improvement in other metabolic and cardiovascular parameters of PCOS women.	Even though a statistically significant reduction in Hcy levels and improved other parameters were observed after treatment with MI+ folic acid, they suggested further studies on a larger population to apply therapy clinically.
9.	Stracquadanio et al. [44]	2018	100 PCOS women	The study aimed to compare clinical, metabolic, endocrine parameters in two treatment groups of PCOS women after six months of continuous therapy. Group A- MI+ gymnemic acid + L methyl folate Group B- MI + folic acid only.	Metabolic assessment in the results showed a significant decrease in Hcy levels and total cholesterol levels in group A.	Study concluded that the combination therapy (MI+ gymnemic acid + L methyl folate) could be a good option for obese PCOS women with marked IR and Hhcy.