Oral Contraceptive Containing Chlormadinone Acetate and Ethinylestradiol Reduces Plasma Concentrations of Matrix Metalloproteinase‐2 in Women with Polycystic Ovary Syndrome

Abstract

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 lg ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.Matrix metalloproteinases (MMPs) are a large endogenous family of proteolytic enzymes that degrade extracellular collagen and participate in vascular remodelling. In addition, the equilibrium between MMPs and their endogenous tissue inhibitors (TIMPs) is crucial for regulating the degradation of extracellular matrix, and its remodelling. MMPs play significant roles in many physiological conditions and are involved in several pathological states, including atherosclerosis.Endothelial dysfunction and increased concentrations of biochemical markers of cardiovascular diseases have been observed in women with polycystic ovary syndrome (PCOS) [1][2][3][4][5][6][7][8]. Several MMPs [9-11], especially MMP-2 and MMP-9 [12][13][14][15], are involved in cardiovascular diseases including atherosclerosis, coronary artery disease and stroke [16][17][18]. Few studies to date, however, have investigated whether the levels of circulating MMPs and TIMPs are altered in women with PCOS [19][20][21][22], although we recently reported that women with PCOS have imbalances in circulating MMPs and that these alterations were associated with excess circulating androgen in these women [22].The first-line pharmacological therapy used in PCOS patients who do not want to conceive is an oral contraceptive (OC) because it effectively r...

Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome

“…The effect of 2 mg CMA and 30 μg EE on FAI in PCOS patients was verified in five studies [ 67 , 73 , 75 , 80 , 81 ], and a significant decrease in FAI ranged from 9.4% to 0.92%, with an average decrease of 8.5% ( p = 0.043). Collectively, these studies indicate that CMA does not counteract the liver’s EE effect on the secretion of SHBG, assure a remarkable decrease in the FAI, and demonstrate that it is an adequate option for the treatment of hyperandrogenemic PCOS patients.…”

“…The influence of COCs containing 30 μg EE and 2 mg CMA on HDL-C concentrations in PCOS patients was examined in three studies only [ 75 , 80 , 81 ]. HDL-C increased from 51.1 mg/dl to 61.4 mg/dl, average of 10.3 mg/dl ( p = 0.108).…”

“…Considering all formulations, fourteen studies reported on the influence of COCs on the systolic blood pressure (SBP) of PCOS patients [ 52 , 59 , 72 , 74 , 75 , 77 , 80 , 81 , 99 – 103 , 105 ]. Four studies reporting on 35 μg EE with 2 mg CPA use demonstrated a nonsignificant increase in the SBP, from 114.2 mmHg to 116.19 mmHg, average increase of 2 mmHg ( p = 0.144) [ 52 , 59 , 77 , 103 ] of women with PCOS.…”

“…Only the Battaglia study demonstrated a significant rise in the SBP [ 72 ]. SBP diminished from 113.9 mmHg to 112.2 mmHg, average decrease of 1.7 mmHg ( p = 0.108) with the use of a COC preparation containing 30 μg EE and 2 mg CMA [ 75 , 80 , 81 ]. Only one single study showed a nonsignificant increase in SBP in PCOS patients that used this preparation [ 80 ].…”

“…SBP diminished from 113.9 mmHg to 112.2 mmHg, average decrease of 1.7 mmHg ( p = 0.108) with the use of a COC preparation containing 30 μg EE and 2 mg CMA [ 75 , 80 , 81 ]. Only one single study showed a nonsignificant increase in SBP in PCOS patients that used this preparation [ 80 ]. Oral contraceptives containing 30 μg EE and 75–150 μg DSG was reported to increase SBP from 107.3 mmHg to 108.2 mmHg, difference of 0.9 mmHg ( p = 0.179) [ 74 , 105 ].…”