Table 4.
Studies with clinical improvements due to drug treatment.
| Drug | Duration | Reference SNPs | Genes | Effect | Cohort origin or ethnicity/PCOS criteria | No. PCOS patients | Ref. | ||
|---|---|---|---|---|---|---|---|---|---|
| Metformin 500 mg 3 times a day plus diet | 6 months | rs1801278 | IRS1 | Lower fasting glucose 17α-OHP and AS was detected (p<0.05). | NS/Rotterdam criteria | 60 | (109) | ||
| Metformin 1000 - 2700 mg/d plus a low calorie diet | 6 months | rs12208357 rs34130495 rs34059508 rs72552763 |
SLC22A1 | Body weight drop menstrual cyclicity improvements, increased SHBG levels and FAI, glucose and insulin levels reduction (p<0.05). | Italy Caucasian/Rotterdam criteria | 150 | (95) | ||
| Metformin 500 mg 3 times a day | 6 months | rs316019 | SLC22A2 | Insulin levels were reduced (p < 0.001) and G/I ratio was increased (p= 0.001). | Taiwan Asian/NS | 87 | (110) | ||
| CC 50 mg/d and dose raising in 50 mg/d each cycle only up to 150 mg/d | NS | rs6166 | FSHR | Higher FSH level (p=0.003) and lower BMI range (p=0.039) induced ovulation on any dose. | 92% Caucasian, 3% Asian, 4% Black/Rotterdam criteria | 193 | (97) | ||
| CC 100 mg/d | 1 cycle | EM *1/*1 *1/*2 *2/*2 *1/*10 |
EM *1/*49 *1/*52 *2/*10 *1/*5 |
IM *10/*10 *10/*41 *10/*49 *5/*10 |
CYP2D6 | Absence of ovulation after the first cycle treatment correlated with lower (E)-clomiphene (active metabolite to induce ovulation) concentration (p=0.036). | Korean Asian/NS | 42 (19 PCOS) |
(107) |
| a) Metformin 1000 mg twice a day b) Metformin with OCP (150 µg DSG + 30 µg EE) |
12 months | rs12208357 rs72552763 |
SLC22A1 | Combined medication was associated with weight reduction (p < 0.001) and increased triglycerides (p < 0.01). | Caucasian/Rotterdam criteria | 40 | (96) | ||
| rs2289669 rs2252281 |
SLC47A1 | ||||||||
| rs12943590 | SLC47A2 | ||||||||
| rs11212617 | ATM | ||||||||
| rs1169288 rs2464196 |
HNF1A | ||||||||
| a) OCP (20 µg EE + 75 µg GSD) b) OCP plus 100 mg/d spironolactone in hirsute women |
6 months | rs2414096 | CYP19 | There was an increase in lipids profile and SHBG. Reduction of testosterone levels FAI, DHEAS, AS, hirsutism score and a mild decline in systolic blood pressure, LH levels and fasting glucose was reported (p < 0.05). | 95% were Caucasian 5% mixed descent/Rotterdam criteria | 162 51 (treated of them 32 showed hirsutism) |
(102) | ||
| a) OCP (20 μg EE + 75 μg of GSD) b) OCP plus 100 mg/d spironolactone hirsute women |
6 months | rs3763676 | HSD17B5 | Reduction in systolic blood pressure glucose, DHEAS, AS, hirsutism score, testosterone levels, FAI and LH levels and an increase in lipids and SHBG was indicated (p<0.05). | 95% Caucasian, 5% African European descent/Rotterdam criteria | 49 | (101) | ||
| a) Metformin 500mg with increments until 1000mg twice a day b) CC 50mg/d (50 mg increment each cycle until 150 mg in poor responders) c) Metformin and CC |
30 weeks or before pregnancy | rs741765 | STK11 | Ovulation rate per cycle or per patient in the metformin group was lower than in the other 2 treatments (p < 0.001). The mean number of ovulations per subject was higher with combined treatment (p < 0.001). |
NS/Rotterdam criteria | 312 | (108) | ||
| rs2234693 | ESR1 | ||||||||
| rs1934963 rs1799853 rs3892097 |
CYP2C9 | ||||||||
| D19S884 | FBN3 | ||||||||
17α-OHP, 17a-hydroxyprogesterone; AS, androstenedione; G/I, glucose/insulin; SHBG, sex hormone binding globulin; FAI, free androgen index; EM, extensive metabolizers; IM, intermediate metabolizers; DSG, desogestrel; EE, ethinyl estradiol; GSD, gestodene; DHEAS, dehydroepiandrosterone sulfate; LH, luteinizing hormone; CC, clomiphene citrate; OCP, oral contraceptive pills; NS, not stated.