Alteration of cardiovascular risk parameters in women with polycystic ovary syndrome who were prescribed to ethinyl estradiol–cyproterone acetate

Purpose  

We aimed to evaluate the alteration of cardiovascular and metabolic risk parameters of polycystic ovary syndrome (PCOS) patients after a 6-month treatment with an oral contraceptive (OC) containing cyproterone acetate (CPA).     

Increased plasma viscosity in young women with polycystic ovary syndrome using an oral contraceptive containing 35 μg ethinyl estradiol and 2 mg cyproterone acetate

Objectives.?To investigate the influence of 6 months of treatment with an oral contraceptive (OC) containing 35?μg ethinyl estradiol and 2 mg cyproterone acetate on plasma viscosity (PV) in young women with polycystic ovary syndrome (PCOS).

Design.?Patients with PCOS were assessed for PV before and after 6 months of treatment with an OC containing 35?μg ethinyl estradiol and 2 mg cyproterone acetate. PV was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C.

Settings.?Subjects were recruited from the Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology at the University Hospital of Patras, Greece.

Patients.?The study included 66 young women with PCOS.

Main outcome measures.?PV.

Results.?In PCOS women as a whole, PV at baseline was 1.249?±?0.049 mm²/s (n?=?66). After 6 months of treatment with an OC containing 35?μg ethinyl estradiol and 2 mg cyproterone acetate, PV was increased to 1.268 ± 0.065 mm²/s (p?=?0.038). The difference between PV before and after 6 months of treatment with an OC containing 35?μg ethinyl estradiol and 2 mg cyproterone acetate (Δviscosity) was 0.01864 ± 0.071452 mm²/s. ΔViscosity was related to Δfibrinogen (r?=?0.270, p?=?0.046), to Δhematocrit (r?=?0.514, p?=?0.09) and to Δtriglycerides (r?=?0.292, p?=?0.021).

Conclusion.?Young women with PCOS presented an increased PV under OC treatment with 35?μg ethinyl estradiol and 2 mg cyproterone acetate.     

The effect of ethinyl estradiol–cyproterone acetate treatment on homocysteine levels in women with polycystic ovary syndrome

Objective Women with polycystic ovary syndrome (PCOS) have multiple risk factors for cardiovascular disease. The cardiovascular risk marker homocysteine (Hcy) is elevated in women with PCOS. This prospective study investigated the effect of oral contraceptives containing ethinyl estradiol–cyproterone acetate (EE–CA) on serum Hcy levels in women with PCOS. Study design A total of 30 women with PCOS were enrolled in this prospective study. The diagnosis of PCOS was made according to the criteria of the Rotterdam PCOS consensus workshop group. All women took oral contraceptives containing EE/CA (35 μg/2 mg) for 3 months. Serum samples for Hcy, lipid profile and hormones were obtained during the early follicular phase (days 3–5) of the spontaneous or progestin-induced bleeding at baseline, and after the third treatment cycle. Results Three months of EE–CA therapy significantly decreased the Hcy levels from 55.97 ± 16.04 to 54.03 ± 16.15 (P = 0.01). A significant correlation was observed between the Hcy and total and free testosterone levels (r = 0.44, P = 0.015 and r = 0.46, P = 0.001 respectively). Conclusions Although the decrease in Hcy levels with EE–CA therapy was statistically significant, further studies are necessary to determine the clinical benefit of this treatment.     

Effect of ethinyl estradiol–cyproterone acetate treatment on asymmetric dimethyl-arginine levels in women with polycystic ovary syndrome

Purpose

Our study was undertaken to evaluate the levels of asymmetric dimethyl-arginine (ADMA) in a group of patients affected with polycystic ovary syndrome (PCOS)—under ethinyl estradiol–cyproterone acetate treatment or not—as compared with a group of healthy controls.

Methods

Fifty-eight women with PCOS and 45 patients as control group were included in the study. The 58 women with PCOS were separated into two groups: Group A (n = 29) were treated with an oral contraceptive pill containing 0.035 mg of ethinyl estradiol (EE) and 2 mg of cyproterone acetate (CA) (Diane-35) for 6 months. Group B (n = 29) did not take any drug. Group C (n = 45) was healthy women as control group. Serum levels of ADMA, lipid and glucose metabolism parameters, hormone profile were measured on the sixth month of treatment.

Results

ADMA levels were similar in women with PCOS and controls, whereas ADMA levels significantly decreased after a period of 6 months treatment with EE + CA in women with PCOS. ADMA levels and insulin resistance were decreased with treatment. However, patients with PCOS had significantly higher total cholesterol and Low-density lipoprotein cholesterol (LDL-C) compared to controls, treatment with EE + CA did not provide any improvement on lipid parameters.

Conclusion

Serum ADMA levels and insulin resistance were lower in PCOS group treated with EE + CA than control group.     

Urinary 6-sulfatoxymelatonin excretion in hyperandrogenic women with polycystic ovary syndrome: the effect of ethinyl estradiol–cyproterone acetate treatment

The role of melatonin in human reproduction is still unknown. Data obtained in patients with hypogonadism and precocious puberty suggest that melatonin and the reproductive hormones are interrelated.The aim of this study was to determine melatonin production in hyperandrogenic women. We studied 12 women with polycystic ovary syndrome (PCOS) and 10 women with idiopathic hirsutism (IH). Patients were treated with cyproterone acetate–ethinyl estradiol (Diane 35) for 4 months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dehydroepiandrosterone sulfate (DHEAS) and 24-h urine collections for the determination of 6-sulfatoxymelatonin (αMT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. The results were compared with those obtained in 15 control women. At baseline, women with PCOS had significantly higher LH and testosterone levels than those with IH and controls. Their αMT6s values (52.6?±?20.3?µg/24?h) were significantly higher than the values in women with IH (34.3?±?7.1) and controls (30.5?±?6.5) (p?<?0.001). Diane 35 treatment significantly decreased LH, FSH, testosterone and αMT6s values in PCOS (28.0?±?13.9?µg/24?h) (p?<?0.0001). These results indicate that women with PCOS have increased melatonin production. The normalization of αMT6s and testosterone values during Diane 35 treatment suggests that sex steroids modulate melatonin secretion in these patients either directly or through the suppression of gonadotropin.     

Do polycystic-appearing ovaries affect the risk of cardiovascular disease among women with polycystic ovary syndrome?

OBJECTIVE: To determine if polycystic-appearing ovaries (PAO) are associated with differences in risk factors for cardiovascular disease among women with polycystic ovary syndrome (PCOS). DESIGN: Case-control sub-study. SETTING: Division of Reproductive Endocrinology, Magee-Womens Hospital. PATIENT(S): Women with PCOS (n = 63) and non-PCOS controls (n = 56). INTERVENTION: Transvaginal ultrasonography and single sample venipuncture. MAIN OUTCOME MEASURE(S): Ultrasound ovarian appearance, fasting insulin, lipoproteins, androgens, LH/FSH ratio, anthropomorphic measurements, and blood pressure. RESULT(S): Women with PCOS had higher androgen and fasting insulin levels, a more adverse lipid profile, greater waist-hip and LH/FSH ratios, and a larger ovarian volume than controls. Thirty-three percent of the cases with PCOS, but only 5% of controls, showed PAO on ultrasound study (P<.01). PCOS cases with and without PAO had comparable levels of fasting insulin, lipids, and blood pressures. PCOS cases with PAO had a higher LH/FSH ratio (P=.028), increased levels of serum androstenedione (P=.029) and testosterone (P=.055), and greater ovarian volume (P=.024) compared to non-PAO patients. CONCLUSION: Women with PCOS have greater cardiovascular risk than controls. Within PCOS cases, however, the ultrasound appearance of polycystic ovaries does not appear to further intensify the cardiovascular disease risk profile of these women.     

Effects of two combined oral contraceptives containing ethinyl estradiol 30 μg combined with either gestodene or drospirenone on hemostatic parameters,lipid profiles and blood pressure

Objective  The aim of this study is to compare the effect of ethinyl estradiol 0.03 mg/gestodene 0.075 mg (EE/GSD) with ethinylestradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) administered according to conventional 21/7 regimen on body mass index (BMI), blood pressure (BP), lipid metabolism and hemostatic parameters. Method  In this study, 160 healthy women were randomized to EE/GSD mg or EE/DRSP for 12 months. Mean differences in BMI, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) levels and BP compared to baseline were assessed. Results  One hundred and forty-five (89%) of the women completed all 12 treatment cycles. The subjects randomly assigned into two treatment groups. Group EE/GSD (n = 71) and group EE/DRSP (n = 72). In group B, BMI values were significantly lower than baseline at the sixth cycle. DRSP/EE had more favorable effects on BP than GSD/EE with the mean systolic and diastolic BPs remaining lower in the DRSP/EE group. The difference between the two preparations was not statistically significant at the end of the study. TC levels remained similar in both groups throughout the study period. In both groups LDL-C levels decreased, triglyceride and HDL-C levels significantly increased from baseline levels. These changes result in increasing HDL-C/LDL-C ratio, demonstrating anti-atherogenic effect. Menstrual cycle patterns and the incidence of adverse events were similar between groups. The duration of withdrawal bleeding decreased during the study for both groups and was similar. Conclusion  The EE/DRSP regimen provides good cycle control with reliable contraceptive efficacy and low incidence of adverse events. Compared with the EE/GSD preparation, the EE/DRSP preparation demonstrated a more favorable effect on BMI and BP with the mean BMI and mean BP remaining lower than baseline mean. The new formulation may be especially beneficial for women susceptible to body weight gain and rise in BP.     

Do women with polycystic ovary syndrome have an increased risk of cardiovascular disease? Review of the evidence

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder found in ~5% of the general population and is characterized by chronic anovulation, hyperandrogenism, and insulin resistance. Women with PCOS are at increased risk for the development of Type II diabetes and may represent a unique group of women at high risk for the development of coronary heart disease (CHD). More adverse CHD risk profiles of women with PCOS have been demonstrated in several studies, yet actual health outcome studies have been inconclusive as to whether this translates into increased rates of cardiovascular disease in PCOS cases when compared to controls. This review focuses on the controversy surrounding the potential relationship between cardiovascular disease outcomes and polycystic ovary syndrome.     

Association of serum glypican-4 levels with cardiovascular risk predictors in women with polycystic ovary syndrome – a pilot study

Objective: Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD).

Design: The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS.

Methods: Sixty-two women with PCOS according to the Rotterdam criteria (20–35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated.

Results: The serum Gpc4 level in PCOS women was significantly higher (2.61?±?1.17?ng/ml) than in the control group (1.55?±?0.47?ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group.

Conclusion: The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.     

Is the suppressive effect of cyproterone acetate on serum anti-Müllerian-hormone levels in women with polycystic ovary syndrome stronger than under oral contraceptive pill?

Objective: To compare the suppressive effect of anti-androgen therapy by cyproterone acetate (CPA) and by oral contraceptive pill (OCP) on anti-müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) in order to detect a putative direct anti-androgen effect on AMH excess.

Methods: This is a prospective longitudinal study including 58 women with PCOS between January 2010 and April 2014 at the Lille University Hospital. A total of 47 women with clinical hyperandrogenism were treated by CPA (50?mg/d was administered 20 days out of 28) and 11 women with PCOS but without clinical hyperandrogenism received OCP.

Result(s): Serum AHM levels at baseline were similar in CPA and OCP groups (median [5–95th percentiles]: 60.4?pmol/l [25.1–200.2] versus 58?pmol/l [27.6–100], respectively, p?=?0.39). After 3 months of treatment, serum AMH levels decreased significantly by 28%?±?20% and by 22%?±?27% in CPA and OCP groups, respectively. The decrease under both treatments was similar (p?=?0.48).

Conclusion(s): That any anti-androgen effect could be observed on AMH in our CPA group in addition to the gonadotropin-suppressing effect suggests that either androgens are not involved in AMH regulation or that they act by interfering with gonadotropin effects on granulosa cells.     

Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3mg administered in a 24/4 regimen: a pooled analysis

Objective

To investigate the effects of an ethinylestradiol (EE) 20 μg/drospirenone (drsp) 3 mg combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets/4 inert tablets per cycle) for the treatment of moderate acne vulgaris, based on a pooled analysis of two identically designed US studies.

Study design

Healthy females (n = 893) aged 14-45 years with moderate facial acne were randomised to EE 20 μg/drsp 3 mg COC (n = 451) or placebo (n = 442) for six cycles. Primary outcome measures were mean percent change in acne lesion counts and the investigators’ assessment of acne from baseline to endpoint.

Results

There were significantly greater reductions in the mean percent change from baseline to endpoint in inflammatory, non-inflammatory and total lesion counts in the EE 20 μg/drsp 3 mg 24/4 COC group compared with the placebo group (P < 0.0001). The odds of women in the EE 20 μg/drsp 3 mg 24/4 COC group having ‘clear’ or ‘almost clear’ skin as rated by the investigators at endpoint were around three-fold greater than in the placebo group (odds ratio 3.41; 95% CI: 2.15-5.43; P < 0.0001).

Conclusions

A low-dose COC containing EE 20 μg/drsp 3 mg (24/4) more effectively reduced acne lesions than placebo and demonstrated greater improvement in the investigator global assessment of acne.     

The effects of different therapeutic modalities on cardiovascular risk factors in women with polycystıc ovary syndrome: A randomızed controlled study

Objective

This study was designed to evaluate the effects of 3 mg drospirenone/30 μg ethinyl estradiol (OC) alone or combined with 1700 mg metformin on metabolic risk factors.

Ethinyl estradiol 20 μg/drospirenone 3 mg 24/4 oral contraceptive for the treatment of functional impairment in women with premenstrual dysphoric disorder

Objective

To determine the effects of ethinyl estradiol (EE)/drospirenone in a 24/4 regimen (24 days of active and 4 days of inactive pills) on functional impairment (affecting work, partnership, and social activities) in women with premenstrual dysphoric disorder (PMDD).

Methods

The present study was a secondary analysis of a double-blind, randomized, parallel-design multicenter trial. Women received EE 20 μg/drospirenone 3 mg (n = 232) or placebo (n = 218) and completed the Daily Record of Severity of Problems (DRSP) scale daily.

Results

The decrease in mean scores for all 3 DRSP functional impairment items (work, partnership, and social activities) from baseline to cycle 3 mirrored changes in the total DRSP symptom score; the greatest decreases were observed in cycle 1 with further small reductions through to cycle 3. The proportional mean decreases from baseline to cycle 1 for the 3 functional items ranged from 47% to 48%. For all 3 functional items, the mean reductions from baseline to cycle 1 (but not from cycle 1 to cycles 2 and 3) were significantly greater with EE/drospirenone than with placebo (P < 0.05).

Conclusion

Ethinyl estradiol 20 μg/drospirenone 3 mg in a 24/4 regimen significantly improved functional impairment in women with PMDD. Symptoms improved in parallel.