Metformin increases pressure pain threshold in lean women with polycystic ovary syndrome

Figures & data

Table 1 Clinical characteristics of lean women with polycystic ovary syndrome and controls at the beginning of the study

Parameter	Total n=45 mean ± SD	PCOS with metformin group (1) n=15 mean ± SD	PCOS without treatment group (2) n=12 mean ± SD	Control group (3) n=18 mean ± SD	P-value
Age (years)	23.3±2.81	23.27±3.24	23.83±2.89	22.89±2.47	P=0.45
Weight (kg)	60±4.5	60.33±3.5	59.83±2.86	60.33±6.08	P=0.38
Height (cm)	167.7±3.78	168.8±1.75	168.8±1.75	166±5.25	P=0.39
BMI (kg/m^2)	21.44±1.47	21.19±1.27	21.1±1.01	21.87±1.8	P=0.63
FT3 (pmol/L)	4.54±0.49	4.41±0.49	4.52±0.42	4.67±0.62	P=0.32
TSH (IU/mL)	1.8±0.59	1.99±0.62	1.51±0.33	1.83±0.64	P=0.45
FT4 (pmol/L)	13.62±2.09	13.01±2.2	13.61±1.4	14.13±2.32	P=0.29
Prolactin (μIU/mL)	248.4±87.14	243.9±87.18	271.5±81.2	236.7±92.7	P=0.22
Estradiol (pmol/L)	276.2±113.7	270.8±113.7	289.8±96.7	271.6±169.1	P=0.11
LH (mIU/mL)	8.85±3.36	11.46±2.74	10.51±1.98	5.57±1.03	P1,2 =0.48, P1,3 <0.001, P2,3 <0.001
FSH (mIU/mL)	6.16±1.14	6.87±1.08	5.99±0.62	5.69±1.2	P1,2 =0.09, P1,3 =0.008, P2,3 =0.72
Testosteron (nmol/L)	1.96±0.76	2.51±0.34	2.51±0.28	1.14±0.42	P1,2 =0.1, P1,3 <0.001, P2,3 <0.001
SHBG (nmol/L)	41.57±8.07	37.59±6.33	39.78±4.43	46.06±9.23	P1,2 =0.72, P1,3 =0.006, P2,3 =0.07
FAI	5.06±2.32	6.97±1.47	6.32±0.45	2.64±1.23	P1,2 =0.33, P1,3 <0.001, P2,3 <0.001
Cortisol-0800 hours (μm/dL)	20.5±7.63	21.5±6.82	20.5±5.82	19.7±5.82	P=0.25
Cortisol-1700 hours (μm/dL)	10.3±4.78	11.3±4.48	10.2±4.67	9.5±4.33	P=0.19
Glucose 0′ (mmol/L)	5.1±0.95	4.8±0.6	5.0±0.86	5.4±1.15	P=0.17
Glucose 60′ (mmol/L)	5.7±1.4	5.5±1.44	5.6±1.34	5.8±1.38	P=0.18
Glucose 120′ (mmol/L)	5.41±1.14	5.1±0.92	5.2±0.94	5.0±1.34	P=0.38
Insulin 0′ (μU/mL)	11.6±5.43	14.4±5.49	14.84±2.45	8.9±3.84	P1,2 =0.54, P1,3 =0.003, P2,3 =0.003
Insulin 60′ (μU/mL)	62.5±34.83	83.8±32.26	85.6±20.21	42.6±24.12	P1,2 =0.43, P1,3 <0.001, P2,3 <0.001
Insulin 120′ (μU/mL)	55.9±35.5	78.2±35.48	76.34±31.3	35.1±19.62	P1,2 =0.32, P1,3 <0.001, P2,3 <0.001
β-Endorphins (pg/mL)	12.01±4.95	16.22±2.04	14.84±2.45	6.61±1.97	P1,2 =0.22, P1,3 <0.001, P2,3 <0.001
PPT deltoid muscle (kg/cm^2)	7.82±2.55	9.56±1	9.91±1.4	4.96±0.55	P1,2 =0.63, P1,3 <0.001, P2,3 <0.001
PPT trapezius muscle (kg/cm^2)	6.79±1.89	7.96±0.98	8.4±0.94	4.74±0.6	P1,2 =0.38, P1,3 <0.001, P2,3 <0.001

Notes: Data are presented as mean ± SD. Analysis was carried out using ANOVA test. Significance level <0.05.

Abbreviations: BMI, body mass index; FT3, triiodothyronine; TSH, thyroid-stimulating hormone; FT4, thyroxin; SHBG, sex hormone-binding globulin; FAI, free androgen index; LH, luteinizing hormone; FSH, follicle-stimulating hormone; PPT, pressure pain threshold; PCOS, polycystic ovary syndrome.

Table 2 ICC, 95% CI, and SEM of PPT values at each measurement point at the beginning of the study and after 6 months observation

Parameter	ICC	95% CI	SEM (kg/cm^2)
PPT-deltoid muscle (beginning of the study)	0.990	0.983–0.994	0.254
PPT-trapezius muscle (beginning of the study)	0.998	0.997–0.999	0.186
PPT-deltoid muscle (after 6 months)	0.990	0.983–0.994	0.188
PPT-trapezius muscle (after 6 months)	0.997	0.999–0.998	0.213

Abbreviations: ICC, intraclass correlation coefficient; CI, confidence interval; SEM, standard error of measurement; PPT, pressure pain threshold.

Figure 1 Estimated marginal means of PPT values measured on deltoid and trapezius muscle at the beginning of the study and after 6 months of observation in all studied groups. Analysis was carried out using ANOVA test with repeated measures. Significance level <0.05.

Abbreviations: PPT, pressure pain threshold; PCOS, polycystic ovary syndrome.

Figure 2 Estimated marginal means of plasma β-endorphins levels at the beginning of the study and after 6 months of observation in all studied groups.

Note: Analysis was carried out using ANOVA test with repeated measures. Significance level <0.05.
Abbreviation: PCOS, polycystic ovary syndrome.

Table 3 Clinical characteristics of lean women from the PCOS with metformin group (1) at the beginning of the study and after 6 months metformin therapy

Parameter	PCOS with metformin group n=15 (beginning of the study)	PCOS with metformin group n=15 (after 6 months metformin therapy)	Mean difference in parameters between 6 months and baseline in PCOS with metformin group	P-value
Weight (kg)	60.33±3.5	59.67±3.46	−0.67±1.54	0.12
BMI (kg/m^2)	21.19±1.27	20.95±1.23	−0.24±0.54	0.11
FT3 (pmol/L)	4.41±0.49	4.51±0.76	0.1±0.52	0.46
TSH (IU/mL)	1.99±0.62	1.98±0.57	−0.01±0.03	0.12
FT4 (pmol/L)	13.01±2.2	13.2±1.7	0.09±0.67	0.63
Prolactin (μIU/mL)	243.9±87.18	239.67±85.17	−4.27±23.62	0.49
Cortisol-0800 hours (μm/dL)	21.5±6.82	19.8±5.08	−1.7±2.65	0.45
Cortisol-1700 hours (μm/dL)	11.3±4.48	10.9±4.34	−0.4±2.12	0.33
Estradiol (pmol/L)	270.8±113.7	270.33±98.42	−0.47±31.3	0.96
LH (mIU/mL)	11.46±2.74	5.55±1.51	−5.91±1.95	<0.001
FSH (mIU/mL)	6.87±1.08	6.79±1.04	−0.08±0.96	0.39
Testosterone (nmol/L)	2.51±0.34	1.8±0.29	−0.71±0.37	<0.001
SHBG (nmol/L)	37.59±6.33	46.7±4.75	9.13±6.51	<0.001
FAI	6.97±1.47	3.91±0.73	−3.06±1.65	<0.001
Glucose 0′ (mmol/L)	4.8±0.6	4.67±0.34	−0.13±0.28	0.47
Glucose 60′ (mmol/L)	5.5±1.44	5.2±0.1.23	−0.3±0.63	0.54
Glucose 120′ (mmol/L)	5.1±0.92	5.0±0.87	−0.1±0.43	0.67
Insulin 0′ (μU/mL)	14.4±5.49	10.2±3.45	−4.4±2.12	<0.001
Insulin 60′ (μU/mL)	83.8±32.26	50.2±28.97	−33.6±14.89	<0.001
Insulin 120′ (μU/mL)	78.2±35.48	43.87±21.23	−34.33±10.3	<0.001
β-Endorphins (pg/mL)	16.22±2.04	15.46±1.82	−0.76±1.93	0.15
PPT deltoid muscle (kg/cm^2)	9.56±1	14.37±0.94	4.81±0.88	<0.001
PPT trapezius muscle (kg/cm^2)	7.96±0.98	13.67±0.76	5.71±1.16	<0.001

Notes: Data are presented as mean ± SD. Analysis was carried out using t-test for dependent samples. Significance level <0.05.

Abbreviations: PCOS, polycystic ovary syndrome; BMI, body mass index; FT3, triiodothyronine; TSH, thyroid-stimulating hormone; FT4, thyroxin; SHBG, sex hormone-binding globulin; FAI, free androgen index; LH, luteinizing hormone; FSH, follicle-stimulating hormone; PPT, pressure pain threshold.