Antonella Napolitano

Combined oral contraceptive containing drospirenone does not modify 24-h ambulatory blood pressure but increases heart rate in healthy young women: prospective study

BACKGROUND Hypertension is a primary cardiovascular risk factor. Oral contraceptives (OCs) may increase blood pressure and cardiovascular events. We evaluated whether an OC containing ethynylestradiol (EE) in association with the spironolactone-derived progestin drospirenone (DRSP) influences 24-h ambulatory blood pressure of normotensive women. STUDY DESIGN Twenty-four-hour blood pressure was measured every 30 min by an ambulatory blood pressure device in 18 normotensive healthy women prior to and after 6 months of use of an OC containing 30 mcg EE and 3 mg DRSP. RESULTS OC induced no modification in 24-h, nighttime and daytime blood pressure. Heart rate increased about 4 beats/min in the 24-h (p<.05) and daytime (p<.02) measurements. CONCLUSIONS In normotensive women, an OC containing 30 mcg EE plus 3 mg DRSP does not modify blood pressure, and significantly increases 24-h and daytime heart rate. These data suggest a neutral effect on hypertension-associated cardiovascular risk and point out an unreported effect on heart rate of which cause and effect require further evaluation.

Pelvic Pain and Quality of Life of Women With Endometriosis During Quadriphasic Estradiol Valerate/Dienogest Oral Contraceptive. A Patient-Preference Prospective 24-Week Pilot Study

Objective: The progestin dienogest (DNG) given alone effectively reduces pelvic pain of women with endometriosis. It is not clear whether the same occurs when DNG is associated with estradiol (E2). Design: Patient preference prospective observational study. Setting: Outpatient centre of university hospital. Patients: 40 patients with endometriosis and menstrual pain. Interventions: 24-week treatment with a quadriphasic association of E2 valerate (E2V) and DNG or a nonsteroidal anti-inflammatory drug (NSAID) to be used only in case of pain (ketoprofene 200-mg tablets). Main Outcome Measures: Menstrual pain and, when present, intermenstrual pain, and dyspareunia were investigated by means of a 10-cm visual analogue scale (VAS). Quality of life was investigated by the short form 36 (SF-36) of the health-related quality of life questionnaire. Results: Final study group consists of 34 patients, 19 in the E2V/DNG group and 15 in the NSAID group. After 24 weeks, no significant modification of menstrual pain, intermenstrual pain, dyspareunia, or SF-36 score was observed in the NSAID group. Treatment with E2V/DNG reduced the VAS score of menstrual pain by 61% (P < .0001). In the subgroups of women with intermenstrual pain or dyspareunia, E2V/DNG reduced these complaints by 65% (P = .013) and 52% (P = .016), respectively. The reduction in menstrual (P = .0001) and intermenstrual pain (p = 0.03) was significantly greater during E2V/DNG than NSAID. Quality of life improved during E2V/DNG (P = .0002), both in physical (P = .0003) and mental domains (P = .0065). Only a few minor adverse effects were described during E2V/DNG, and none caused withdrawal from treatment. Conclusion: In patients with endometriosis and pelvic pain, the 24-week administration of the quadriphasic association of E2V/DNG decreases pelvic pain and improves quality of life.

Modification of 24-h ambulatory blood pressure and heart rate during contraception with the vaginal ring: a prospective study

BACKGROUND Hypertension is recognized as a major risk factor for coronary, cerebral and renal vascular disease. Hormonal methods of contraception may increase the risk for cardiovascular events. We evaluated whether the combined hormonal contraceptive vaginal ring that releases 15-mcg ethinylestradiol and 120 mcg of etonogestrel each day influences 24-h ambulatory blood pressure. STUDY DESIGN At baseline, ambulatory blood pressure was automatically monitored every 30 min for 41 h in 18 normotensive healthy women during their follicular phase (Days 3-6). Each subject was immediately treated with the vaginal ring for six cycles. Monitoring of ambulatory blood pressure was repeated in the last days of the sixth cycle of treatment. RESULTS During the vaginal ring, a significant increase was observed for 24-h diastolic (2.75±5.13 mmHg; p=.03) and mean (2.69±5.35 mmHg; p=.048) blood pressure and for daytime diastolic (3.04±6.36 mmHg; p=.05) blood pressure. No variation was found in nighttime blood pressure. Heart rate increased in the 24-h period (3.39±5.85 beats/min; p=.025) and in the daytime (3.38±6.25 beats/min; p=.034) measurements. CONCLUSIONS In normotensive women, the vaginal ring slightly increases 24-h blood pressure and heart rate. The underlying mechanisms and the clinical impact of these slight modifications require further evaluation.

Prospective measurement of blood pressure and heart rate over 24 h in women using combined oral contraceptives with estradiol.

OBJECTIVE Combined oral contraceptives (COCs) containing ethinyl-estradiol are known to increase blood pressure (BP). We evaluated whether COCs containing estradiol (E2) influence 24-h ambulatory BP and heart rate (HR) in normotensive and normal-weight women. STUDY DESIGN Twenty-four-hour BP and HR were measured every 30 min with an ambulatory BP device in 18 normotensive healthy non-smoking women prior to (Days 3-6 of menstrual cycle) and after 6 months of use (Days 20-24 of cycle 6) of a COC containing either a quadriphasic combination of E2 valerate plus dienogest (n=11) or a monophasic association of micronized E2 plus nomegestrol acetate (n=7). RESULTS Mean age and body mass index of the final sample were 32.50±7.49 years and 22.87±4.08, respectively. E2-based COCs induced no modification of 24-h systolic BP (+1.65±8.34 mmHg; p=.41), diastolic BP (+0.04±7.36 mmHg; p=.98), mean BP (+0.64±6.42 mmHg; p=.68) or HR (-0.72±5.86 beats/min; p=.61). Differences were not observed even when daytime or nighttime values were separately considered. Though this was not a comparative study, we did not find differences between the effects of the two formulations (24-h mean BP; p=.699). CONCLUSIONS These data suggest a neutral effect of estradiol-based COCs on independent risk factors for cardiovascular diseases such as BP or HR. IMPLICATIONS BP and HR of normotensive women are not increased by E2-based COCs.

Metabolic impact of combined hormonal contraceptives containing estradiol

ABSTRACT Introduction: Is the replacement of ethinyl-estradiol (EE) with estradiol (E2) in combined hormonal contraceptives (CHCs) associated with fewer metabolic effects, leading to a further improvement on safety of hormonal contraceptives? Areas covered: This is a narrative review paper including all available data on the metabolic impact of CHCs containing E2 published in English up to December 2015. Modification of a metabolic variable of interest during the first months of treatment was considered as an outcome. Expert opinion: E2 was extensively used in oral contraceptives associated to nomegestrol acetate (NOMAc) in a monophasic 24 + 4 or its ester E2 valerate to dienogest (DNG) in a quadriphasic 26 + 2 regimen. The impact on the lipid metabolism and the hemostatic system of these preparations seems milder than that caused by EE-based ones, associated with no change of blood pressure. The impact on bone metabolism was instead similar to EE. Data available in the literature are mainly derived from studies having secondary minor metabolic outcomes as the primary end-point, and so currently not completely applicable on the real variables of interest (arterial or venous cardiovascular events, bone fractures). The preliminar parenteral use of E2 seems promising, both transdermal and vaginal, in particular after the introduction of a specific progestin with a high anti-ovulatory activity, like nestorone.

Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea

Abstract Objective: To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on metabolism and health-related quality of life were also evaluated. Design: Prospective observational cohort study. Setting: Tertiary gynecologic center for pelvic pain. Patients: Subjects with primary dysmenorrhea requiring an oral contraceptive, who spontaneously selected either E2/NOMAC (n = 20) or EE/CMA (n = 20). Main outcome measures: Visual Analogue Scale (VAS) score for dysmenorrhea, Short Form-36 questionnaire for health-related quality of life, lipoproteins and days of menstrual bleeding (withdrawal bleeding during oral contraceptive). Results: Mean age and body mass index (BMI) were similar between the two groups. The final analysis was performed on 34 women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance with treatment was significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p = 0.02). Both treatments significantly (p < 0.0001) reduced VAS of primary dysmenorrhea, similarly (E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p = 0.973). Only E2/NOMAC significantly increased SF-36 score (p = 0.001), both in physical (p = 0.001) and mental domains (p = 0.004). The mean number of days of menstrual bleeding was significantly reduced in E2/NOMAC group (from 4.86 ± 1.20 d to 2.64 ± 1.59 d, p = 0.0005 versus baseline, p = 0.007 versus EE/CMA group). BMI did not vary in either group. E2/NOMAC did not change lipoproteins and apoproteins while EE/CMA increased total cholesterol (p = 0.0114), HDL-cholesterol (p = 0.0008), triglycerides (p = 0.002), apoprotein-A1 (Apo-A1; p = 0.0006) and apopoprotein-B (Apo-B; p = 0.008), decreasing LDL/HDL ratio (p = 0.024). Conclusions: Both oral contraceptives reduced similarly primary dysmenorrhea, with E2/NOMAC also reducing withdrawal bleedings and being neutral on lipid metabolism.

Body composition and resting metabolic rate of perimenopausal women using continuous progestogen contraception

Objective The effect on body composition and in particular on fat mass (FM) of 12 months’ use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause. Methods An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months. Results FM did not change in the control group (− 0.5 ± 1.6%) but significantly increased in the LNG-IUS group (+ 1.1 ± 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8 ± 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG or the LNG-IUS showed a non-significant increase in body weight, body mass index and waist circumference. RMR did not significantly vary in the control group (− 3.8 ± 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG-IUS (115.5 ± 531.8 kJ/ 24 h) and DSG groups (305.9 ± 556.9 kJ/24 h). Conclusions The results of this preliminary study seem to indicate that in perimenopausal women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may favour FM accumulation.

From Menopause to Aging: Endocrine and Neuroendocrine Biological Changes

Aging is strongly related to the female hormonal status; indeed it is well known how relevant the impact of the hormonal deficiency in the postmenopause is on the general health of the woman. Aging and in particular the menopause transition are associated with the occurrence of the typical symptoms related to estrogen deficiency such as vasomotor, genitourinary, and musculoskeletal symptoms [1–3]. In this period women become markedly vulnerable to cardiovascular diseases and neurodegenerative disorders that, at this moment of women’s life, occur more frequently than in men [4]. With the increase of life expectancy, in 2025 it is expected that there will be more than 1.1 billion in postmenopausal women and most of them will suffer from eating disorders and menopausal-related symptoms (Fig. 2.1).

Association between pelvic organ prolapse and climacteric symptoms in postmenopausal women

OBJECTIVE To evaluate whether climacteric symptoms are related to pelvic organ prolapse (POP) in postmenopausal women. STUDY DESIGN A cross-sectional investigation was performed on 1382 postmenopausal women attending an outpatient service for menopause at a university hospital. MAIN OUTCOME MEASURES Data regarding climacteric symptoms, as captured by the Greene Climacteric Scale, and objective POP were retrieved from an electronic database. Additional data retrieved were age, anthropometric measures, personal and reproductive history, use of medication or drugs, coffee, smoking, state of anxiety (STAI scale score) and depression (Zung scale score). RESULTS The score of Greene Climacteric Scale was higher (p=0.02) in women with (n=538) than in those without (n=844) POP (29.6±13.6 vs. 27.8±13.; p=0.02). In multiple logistic regression models, the score was independently related to POP as a whole (OR 1.012; 95%CI 1.003,1.022; p=0.009), and to bladder prolapse (OR 1.011; 95%CI 1.007,1.07; p=0.02) or to uterus prolapse (OR 1.003; 95%CI 0.99,1.016; p=0.63) or rectum prolapse (rectocele) (OR 1.004; 95%CI 0.988,1.02; p=0.62). CONCLUSIONS In postmenopausal women, a higher burden of climacteric symptoms, is associated with POP. Underlying mechanisms were not assessed and deserve further investigation.