Effect of oral contraceptives containing 20 and 35 μg ethinyl estradiol on urinary prostacyclin and thromboxane levels in smokers and non-smokers

Objective: Several observational epidemiological studies have shown an increased risk of myocardial infarction (MI) in oral contraceptive (OC) users who smoke cigarettes. Nearly a quarter of all OC users are smokers. The etiology of MI in OC users has been shown to be thrombotic, and the thrombogenic effect of OCs appears to be due to the estrogen component of the formulation. There are epidemiologic data that indicate that decreasing the estrogen dosage in OCs decreases the risk of thrombosis. Smoking may enhance thrombosis in OC users by decreasing prostacyclin levels. The objective of the present study was to investigate the interaction between smoking and OC use with respect to thrombogenesis by studying the effects of OCs and smoking on urinary levels of prostacyclin PGI and thromboxane A₂ TX in smokers and non-smokers.Study Design: A total of 60 healthy women, aged 19–32 years, who were not taking any hormonal treatment for at least 3 months prior to initiating the study were divided into three equal groups: A) OC users who smoked (N = 20), B) OC users who did not smoke (N = 20), and a control group of 10 smokers and 10 non-smokers. To be eligible to participate in the study, all smokers had to smoke at least one pack of cigarettes per day. Each OC treatment group was randomized to receive either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE₂) (0.035 mg) (N = 10) or NET acetate (1 mg)/EE₂ (0.02 mg) (N = 10) daily for 3 months. Overnight urine collections and fasting blood samples were obtained at baseline and at 3 months prior to taking the last OC. Serum levels of NET and EE₂, as well as urinary levels of cotinine and the stable metabolites of prostacyclin and thromboxane A₂ (6-keto-prostaglandin F_1α and thromboxane B₂, respectively), were measured by specific immunoassays.Results: Study subjects showed compliance with respect to smoking and OC use as determined by the levels of serum NET, EE₂, and cotinine. Comparing mean levels of PGI metabolites in the two groups of OC smokers, those taking 35 μg EE₂ showed a significant decrease in PGI. Comparing the ratio of PGI/TX in all smokers, only the smokers on the 35 μg formulation showed a significant decrease in the ratio, while there was no change in the 20 μg group. No significant changes in the ratio PGI/TX during the same time interval in smoking and non-smoking controls and OC non-smokers were observed.Conclusions: Women smokers taking 20 μg EE₂ OC had no thrombophilic changes of PGI and TXA₂ metabolites. Women smokers taking 35μg EE₂ oral contraceptive had thrombophilic changes in PGI/TXA metabolite ratio. Women smokers who use oral contraceptives may have less thrombotic risk taking formulations with 20μg EE₂ than 35μg EE₂.     

Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol

Objective?To compare the effects on ovarian activity of two oral contraceptives containing nomegestrol acetate (NOMAC)/17β-oestradiol (E2) or drospirenone (DRSP)/ethinylestradiol (EE).

Methods?In this open-label, randomised, six-cycle study, 32 subjects using NOMAC/E2 (2.5–1.5?mg; 24/4-day regimen) were compared to 16 subjects using DRSP/EE (3 mg–30?μg; 21/7-day regimen). Measurements included serum oestradiol, progesterone, follicle stimulating hormone (FSH) and luteinising hormone (LH), and ultrasonography of follicular diameter.

Results?No ovulations occurred during treatment. Progesterone was fully suppressed, with mean maximum values?<2 nmol/l in both groups over all cycles. For NOMAC/E2, mean maximum follicular diameter decreased from 19.3?mm before treatment to between 6.9 and 8.2?mm during treatment, with no subject having a follicular diameter ≥15?mm. For DRSP/EE, a decrease from 19.6 to between 7.4 and 10.8?mm was observed, with two subjects (12.5%) having a maximum follicle diameter ≥15?mm. These findings were consistent with observed FSH reductions; full suppression of LH surges was observed in both groups. Post-treatment return of ovulation in both groups occurred on average 21 days after the last active tablet intake.

Conclusions?NOMAC/E2 achieves consistent ovulation inhibition, with suppressive effects on the ovaries at least similar to those of DRSP/EE.     

Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen,in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen

ABSTRACT

Objectives The primary objective was to assess the efficacy, cycle control and tolerability of a monophasic combined oral contraceptive (COC) containing nomegestrol acetate (NOMAC) and 17β-oestradiol (E2). Effects on acne were evaluated as a secondary objective. Results were compared to those of a COC containing drospirenone (DRSP) and ethinylestradiol (EE).

Methods Women (aged 18–50 years) were randomised to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n = 1591) or DRSP/EE (3 mg/30 μg) in a 21/7-day regimen (n = 535) for 13 cycles.

Results Estimated Pearl Indices for NOMAC/E2 and DRSP/EE were 0.38 and 0.81 in women aged ≤ 35 years and 0.31 and 0.66 for all women (18–50 years), respectively. Scheduled withdrawal bleedings were shorter and lighter among users of NOMAC/E2 and were sometimes absent altogether. Intracyclic bleeding/spotting was infrequent in both groups, and decreased over time. Type and frequency of adverse events were similar to those typically reported for COCs.

Conclusions These data show that NOMAC/E2 provides high contraceptive efficacy with acceptable cycle control as well as an overall adverse event profile similar to that of DRSP/EE.     

Clinical trial of a monophasic estroprogestin oral formulation containing 20 μg ethinyl estradiol and 75 μg gestodene

The attempt to decrease the hormonal components of combined estrogen/progestin-containing oral formulations has led to use of low-dose formulations. The monophasic formulation containing ethinyl estradiol 20 μg (EE20) plus gestodene 75 μg (GSD75) was studied in an open ,non-comparative ,multicenter ,clinical trial investigating its efficacy ,safety ,effects on body weight ,blood pressure and sexual function. To evaluate the impact on sexual function ,the Golombok Rust Questionnaire on Sexual Satisfaction (GRISS) was used. The study population comprised 216 women treated for 1 year. The EE20/GSD75 formulation did not show any significant effect on blood pressure ,hematological parameters ,body weight or sexual function. The treatment was well tolerated with a high compliance rate by the patients, with a low rate of estrogen-dependent symptoms. Moreover ,there was no overall effect on sexual function ,with no disturbance of sexual behavior or activity. In conclusion ,our data show that the EE20/GSD75 has a very good tolerability profile ,without any significant side-effects.     

A comparison of the cycle control and tolerability of two ultra low-dose oral contraceptives containing 20 μg ethinylestradiol and either 150 μg desogestrel or 75 μg gestodene

Objective To compare the cycle control and tolerability of two oral contraceptives containing 20 μg ethinylestradiol and either 150 μg desogestrel or 75 μg gestodene.

Methods A randomized, multicenter study was conducted in which 1016 healthy adult women received the desogestrel (n = 509) or the gestodene (n = 507) preparation for six treatment cycles.

Results No significant differences in bleeding patterns were detected between the two treatments. The incidence and duration of irregular bleeding decreased markedly, and to a similar extent, during each treatment. The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4% in the desogestrel group and from 19.7 to 8.6% in the gestodene group. Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days, respectively. There was a consistently low incidence of amenorrhea (1.0–2.8%). There were no significant differences between treatments for the incidence, intensity or emergence of dysmenorrhea. During both treatments, the incidence of premenstrual syndrome and complaints such as breast tenderness, nausea and headache dropped markedly.

Conclusion Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent, good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar, excellent tolerability profiles.     

Efficacy on climacteric symptoms of a continuous combined regimen of 1 mg 17β-estradiol and trimegestone versus two regimens containing 1 or 2 mg 17β-estradiol and norethisterone acetate

Objectives.?To compare the efficacy of a continuous combined regimen of 1?mg 17β-estradiol (17β-E₂) and 0.125?mg trimegestone (TMG) with two continuous combined 17β-E₂/norethisterone acetate (NETA) combinations in the relief of climacteric symptoms in postmenopausal women.

Study design.?This was a randomized, double-blind, multicenter study conducted in 13 countries over a 2-year period. Healthy postmenopausal women with an intact uterus were treated with 1?mg 17β-E₂/0.125?mg TMG, 2?mg 17β-E₂/1?mg NETA or 1?mg 17β-E₂/0.5?mg NETA for up to 26 cycles, each of 28 days.

Results.?The 1?mg 17β-E₂/0.125?mg TMG combination was effective in significantly reducing the mean daily number and severity of hot flushes and in reducing the number of night sweats from cycle 1 onward. No overall significant differences between this regimen and the comparators were detected. Other efficacy variables, including the Kupperman index, psychofunctional disorders and quality-of-life sub-scales, experienced a similar improvement from baseline with all treatments.

Conclusion.?Continuous combined 1?mg 17β-E₂/0.125?mg TMG provides relief of menopausal symptoms that is non-inferior to both 17β-E₂/NETA combinations. Furthermore, trimegestone appeared to provide a better improvement of depressive mood than 0.5?mg NETA when combined with 1?mg 17β-estradiol.     

A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 μg ethinylestradiol and either 2 mg chlormadinone acetate or 150 μg desogestrel

Objectives To determine the effect of two low-dose monophasic oral contraceptives containing either 2 mg chlormadinone acetate or 150 μg desogestrel on blood clotting and fibrinolysis.

Methods In vivo markers of intravascular coagulatory and fibrinolytic activity were measured in 45 volunteers randomly assigned to a 6-month treatment with one of the two study preparations.

Results During oral contraceptive use, the procoagulatory activity increased (increased prothrombin fragment 1+2), the anticoagulatory capacity changed (increased protein C activity, decreased activated protein C sensitivity, decreased protein S activity and decreased antithrombin III activity) and the fibrinolytic system was activated (increased concentrations of plasmin-antiplasmin complexes and d-dimer as well as total fibrin degradation products). There were no relevant differences between the two medication groups.

Conclusion Our results demonstrate that both oral contraceptive preparations have comparable effects on the hemostatic system. There was a shift towards a new equilibrium of hemostatic activities, both coagulatory and fibrinolytic, at a higher turnover rate. Changes did not exceed the range of normal variation and were comparable to the published effects of other low-dose oral contraceptives. There was no evidence of a differential risk of deep vein thrombosis between the two preparations.     

Effects of an extended flexible regimen of an oral contraceptive pill containing 20 μg ethinylestradiol and 3 mg drospirenone on menstrual-related symptoms: a randomised controlled trial

Objectives: The aim of the study was to assess the efficacy for menstrual-related symptoms of an extended flexible regimen of an oral contraceptive pill containing 20?μg ethinylestradiol and 3?mg drospirenone in comparison with a 24/4 d cyclical regimen of the same formulation.

Methods: This randomised, non-inferiority, open-label, multicentre study was conducted in women aged 18–39 years. Their menstrual-related symptoms were assessed using the Penn Daily Symptom Rating (DSR17). Participants were randomised to use an extended flexible regimen of 20?μg ethinylestradiol and 3?mg drospirenone (EE/DRSP_e.flex), comprising 168 consecutive days with a 4-d hormone-free interval (HFI, allowing for management of unexpected bleeding) or a conventional 24/4 cyclical regimen of the same pill (EE/DRSP_24/4). The primary measure of efficacy was the percentage change in DSR17 total score from baseline to cycle 6. The secondary measures of efficacy were the percentage changes in DSR17 total score from baseline after each 28-d interval throughout the entire study and in the scores for individual DSR17 symptoms.

Results: The primary analysis demonstrated that EE/DRSP_e.flex was not inferior to EE/DRSP_24/4 (Mean DSR17 score 9.1; 95% confidence interval (CI)???2.5, 20.6; p?=?0.123). Analysis at intervals throughout the entire evaluation period showed greater reduction in DSR17 total score for EE/DRSP_e.flex than for the 24/4 regimen (p?p?Conclusion: The extended flexible regimen was not inferior to the 24/4 cyclical regimen in terms of the primary endpoint. It significantly improved symptoms in the interval analysis, and the effects on specific DSR17 symptoms, compared with the cyclical regimen.     

Blood pressure stability in a normotensive population during intake of a monophasic oral contraceptive containing 20 μg ethinylestradiol and 75 g gestodene

Objectives Evaluation of the impact of a monophasic gestodene-based oral contraceptive on blood pressure in a population that was normotensive at baseline. Methods Data on blood pressure were retrospectively analyzed from four large prospective clinical phase III trials with an oral contraceptive containing 20 μg ethinylestradiol and 75 μg gestodene. A total of 1342 young fertile women were evaluated after 12 treatment cycles. Results The mean systolic and diastolic blood pressure did not change during treatment. Approximately 89% of women were normotensive at baseline and 93% at the end of the treatment period. Only a few women (≤ 1%) were hypertensive at baseline; an increase in this prevalence was not found after 12 cycles of oral contraceptive use. The number of women who experienced a blood pressure increase was almost identical to the number who experienced a decrease. Approximately 90% of women had either a negligible blood pressure change of maximal ± 10 mmHg or a decrease. Conclusions The findings of this retrospective analysis confirm that monophasic gestodene has a negligible effect on blood pressure in users who were normotensive before treatment began.     

Effects on body weight and body composition of a low-dose oral estroprogestin containing ethinyl estradiol 20 μg plus levonorgestrel 100 μg

Weight gain is a common problem reported by users of estroprogestins (EPs) and is a frequent reason for EP discontinuation, even if this problem is not confirmed in several clinical studies. We studied the impact of a EP containing ethinyl estradiol (EE) 20 μg plus levonorgestrel (LNG) 100 μg on body weight (BW) and body composition in 47 treated women and 31 women as controls. Also, we studied the effect of this association on metabolic parameters (glycemia, lipid profile). EE20/LNG100 had no significant impact on body weight, body composition (fat mass, fat-free mass, total body water, intracellular water, extracellular water) or metabolic profile in comparison with no treatment. Thus, the use of EE20/LNG100 showed no impact on metabolic parameters, body weight and body composition. This could be important not only for the safety profile of this combination, but also in increasing patient compliance.     

The influence of women’s fear, attitudes and beliefs of childbirth on mode and experience of birth

Background

Knowledge, attitudes and practices of community members and healthcare providers in rural northern Ghana regarding clean delivery are not well understood. This study explores hand washing/use of gloves during delivery, delivering on a clean surface, sterile cord cutting, appropriate cord tying, proper cord care following delivery, and infant bathing and cleanliness.

Methods

In-depth interviews and focus group discussions were audiotaped, transcribed, and analyzed using NVivo 9.0.

Results

253 respondents participated, including women with newborn infants, grandmothers, household and compound heads, community leaders, traditional birth attendants, and formally trained health care providers. There is widespread understanding of the need for clean delivery to reduce the risk of infection to both mothers and their babies during and shortly after delivery. Despite this understanding, the use of gloves during delivery and hand washing during and after delivery were mentioned infrequently. The need for a clean delivery surface was raised repeatedly, including explicit discussion of avoiding delivering in the dirt. Many activities to do with cord care involved non-sterile materials and practices: 1) Cord cutting was done with a variety of tools, and the most commonly used were razor blades or scissors; 2) Cord tying utilized a variety of materials, including string, rope, thread, twigs, and clamps; and 3) Cord care often involved applying traditional salves to the cord - including shea butter, ground shea nuts, local herbs, local oil, or ??red earth sand.?? Keeping babies and their surroundings clean was mentioned repeatedly as an important way to keep babies from falling ill.

Conclusions

This study suggests a widespread understanding in rural northern Ghana of the need for clean delivery. Nonetheless, many recommended clean delivery practices are ignored. Overarching themes emerging from this study included the increasing use of facility-based delivery, the disconnect between healthcare providers and the community, and the critical role grandmothers play in ensuring clean delivery practices. Future interventions to address clean delivery and prevention of neonatal infections include educating healthcare providers about harmful traditional practices so they are specifically addressed, strengthening facilities, and incorporating influential community members such as grandmothers to ensure success.     

Accuracy of 30‐Day Recall for Components of Sexual Function and the Moderating Effects of Gender and Mood

IntroductionDespite the ubiquity of 1‐month recall periods for measures of sexual function, there is limited evidence for how well recalled responses correspond to individuals' actual daily experiences.AimTo characterize the correspondence between daily sexual experiences and 1‐month recall of those experiences.MethodsFollowing a baseline assessment of sexual functioning, health, and demographic characteristics, 202 adults from the general population (101 women, 101 men) were recruited to complete daily assessments of their sexual function online for 30 days and a single recall measure of sexual function at day 30.Main Outcome MeasuresAt the baseline and 30‐day follow‐ups, participants answered items asking about sexual satisfaction, sexual activities, interest, interfering factors, orgasm, sexual functioning, and use of therapeutic aids during the previous 30 days. Participants also completed a measure of positive and negative affect at follow‐up. The main outcome measures were agreement between the daily and 1‐month recall versions of the sexual function items.ResultsAccuracy of recall varied depending on the item and on the gender and mood of the respondent. Recall was better (low bias and higher correlations) for sexual activities, vaginal discomfort, erectile function, and more frequently used therapeutic aids. Recall was poorer for interest, affectionate behaviors (e.g., kissing), and orgasm‐related items. Men more than women overestimated frequency of interest and masturbation. Concurrent mood was related to over‐ or underreporting for six items addressing the frequency of masturbation and vaginal intercourse, erectile function, and orgasm.ConclusionsA 1‐month recall period seems acceptable for many aspects of sexual function in this population, but recall for some items was poor. Researchers should be aware that concurrent mood can have a powerful biasing effect on reports of sexual function. Weinfurt KP, Lin L, Dombeck CB, Broderick JE, Snyder DC, Williams MS, Fawzy MR, and Flynn KE. Accuracy of 30‐day recall for components of sexual function and the moderating effects of gender and mood. J Sex Med 2014;11:678–696.     

The effects of two progestogen-only pills containing either desogestrel (75 μg/day) or levonorgestrel (30 μg/day) on carbohydrate metabolism and adrenal and thyroid function

Objective To compare the effects of two progestogen-only pills, containing either desogestrel or levonorgestrel, on carbohydrate metabolism, and adrenal and thyroid function. Methods In a double-blind, randomized, multicenter study in Finland, 84 healthy female volunteers received either desogestrel 75 μg/day or levonorgestrel 30 μg/day for seven treatment periods of 28 days. The following laboratory parameters were measured at screening, and at treatment periods 3 and 7: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin (HbA₁C)), adrenal function (total cortisol, cortisol binding globulin (CBG), dehydroepiandrosterone sulfate (DHEAS)), thyroid function (thyroid stimulating hormone, free thyroxine). Results Overall, the effect on carbohydrate metabolism was minimal with both study medications. There was a trend for higher glucose and insulin values for the levonorgestrel group at both treatment periods 3 and 7. None of the changes were thought to be clinically relevant. Both preparations had similar small effects on HbA₁C values, indicating that carbohydrate metabolism was not affected. No effects were found on thyroid function parameters or DHEAS in either treatment group; however, total cortisol and CBG were slightly higher with desogestrel than with levonorgestrel. These changes were not considered to be clinically relevant. Both treatments were well tolerated. Conclusions The effects of both progestogen-only pills on carbohydrate metabolism were minimal and considered to be clinically insignificant. With regard to adrenal and thyroid function, the effects of desogestrel were not significantly different from those of levonorgestrel.     

A multicenter,randomized comparative trial of the clinical effects on cycle control of two 21-day regimens of oral contraceptives containing 20 μg EE

Purpose: This multicenter, randomized, open-label comparative study was designed to evaluate the effects on cycle control of the only two oral contraceptives (OCs) containing 20 μg ethinyl estradiol (EE) that are available in North America.Methods: Women of childbearing age who desired OCs for birth control were eligible to enroll in this study. Sixty-two subjects were randomly assigned to receive Alesse™ (levonorgestrel 0.1 mg and EE 20 μg) or Loestrin Fe 1/20® (norethindrone acetate 1.0 mg and EE 20 μg).Results: At the time of the interim analysis data cut-off 32 subjects had completed 3 cycles of Alesse and 30 had completed 3 cycles of Loestrin Fe 1/20. The groups were similar with regard to age, weight, height, race, and prior OC usage. A total of 22% of the subjects in the levonorgestrel group and 27% of those subjects in the norethindrone group had never used OCs. The remainder had not used OCs for at least 3 months before entering the trial. During the third cycle of use, the percentage of normal cycles was significantly greater in the levonorgestrel group (P < .05). Moreover, the rate of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone group (62.9%) was more than double that in the levonoregestrel group (29.0%). Cumulatively, from cycles 1 to 3, there was a higher incidence of absence of withdrawal bleeding with norethindrone when compared with levonorgestrel (27.7% vs 5.3%).Conclusion: The results of this study demonstrate that good cycle control can be achieved with an OC containing 20 μg EE. The superior cycle control of Alesse compared with Loestrin Fe 1/20 is consistent with that found in comparative studies of the cycle control of levonorgestrel, norethindrone, and norethindrone acetate containing OCs that had a higher dose of EE.     

Conventional vs. extended-cycle oral contraceptives on the quality of sexual life: comparison between two regimens containing 3 mg drospirenone and 20 µg ethinyl estradiol

IntroductionWomen may use new oral contraceptives (OC) having flexible extended-cycle regimens with a reduced hormone-free interval.AimTo study the changes of the quality of sexual life in users of the traditional 21/7 or extended-cycle 24/4 OC regimens both containing 3 mg drospirenone and 20 µg ethinyl estradiol.MethodsOne hundred fifteen women (age range 18–37 years) were enrolled. Fifty-four women were randomly placed on traditional OC standard regimen, administered for 21 days, followed by a 7-day hormone-free interval (group A); and 61 women were placed on extended-cycle OC regimen covering 24 days of the cycle with a 4-day hormone-free interval (group B).The Short Form-36 (SF-36) validate questionnaire to assess quality of life (QoL) and the Short Personal Experience Questionnaire (SPEQ) to measure the changes of sexual behavior were administered before starting OC intake and at the 3rd and 6th cycle follow-ups.Main Outcome MeasureThe SF-36 and the SPEQ questionnaires.ResultsGroup A women reported QoL improvement during the 6th cycle on all the scales (P < 0.05). Group B women reported QoL improvement during the 3rd and 6th cycle (P < 0.05). Satisfaction with sexual activity, arousal, orgasm, and desire increased during the 3rd cycle in women on the group B (P < 0.05). Group A women did not report any change in all SPEQ items. At the 6th cycle, group B women reported better sexual experience than baseline in all SPEQ items (P < 0.05). All subjects who were affected by dyspareunia before OC intake reported decreased genital pain associated with intercourse at the 3rd and 6th cycle of both OC regimens (P < 0.05).ConclusionWomen could use OCs in a subjective flexible modality. The extended-cycle OC might produce positive effects on the quality of sexual life, enforcing the concept of tailoring an OC to a woman. Caruso S, Iraci Sareri M, Agnello C, Romano M, Lo Presti L, Malandrino C, and Cianci A. Conventional versus extended-cycle oral contraceptives on the quality of sexual life: comparison between two regimens containing 3 mg drospirenone and 20 µg ethinyl estradiol.