Oral Contraceptive Regimen Research Articles

Impact of Continuous Estroprogestin Treatment on Circulating Microparticle Levels in Deep Endometriosis Patients.

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.

Effects of oral contraceptive pill on female health

Oral contraceptives, also known as birth control tablets/pills, are medicines that stop pregnancy. About 75% of married women who use contraception in the research location (Purba Medinipur district) reported they prefer the combined hormonal pill with oestrogen and progesterone. Thirty women were chosen at random to participate in the study. Of the 50% who routinely used contraceptive pills and 50% never used them or occasionally did so. Her male partner likely uses a condom when necessary. The hormone progesterone is responsible for preventing conception, whereas the oestrogen component regulates menstrual blood loss. An questionnaire survey is used in one-on-one interviews. Statistics used in the study were descriptive. To examine the data, an unpaired ‘t’ test was employed. In order to provide effective contraception using oral contraceptives, this study investigates the adverse effects of oral contraceptive pills. It highlights the significance of better care coordination among occupational therapist. According to this study, one of the most common oral contraceptive regimens decreases women's quality of life while not affecting depressive symptoms. However, ovarian and menstrual issues and increased bone mineral density are very noticeable in women in their forties and significantly impact their behaviour. Younger women are more receptive to oral contraceptives' positive benefits on acne. It has been shown that birth control pill side effects can include complications including cystic acne, anxiety or irritability, sore breasts, weight gain, or some trouble conceiving after discontinuing the pill. The study makes predictions about the menstrual flow type, dysmenorrhea, blood pressure, waist-hip ratio, and pattern of contraceptive use. Consuming oral contraceptives is linked to some symptoms, including breast soreness, weight gain, missing periods, vaginal discharge, alterations in vision with contact lenses, and irregular or spotty bleeding.

Bleeding Patterns with Use of an Oral Contraceptive Containing Estetrol and Drospirenone: Pooled Analysis of Phase-3 Clinical Trials

To evaluate bleeding patterns with use of a 24/4-day novel combined oral contraceptive regimen containing estetrol, a natural estrogen, and drospirenone.

Prescription de contraception æstro-progestative en schéma continu/étendu/flexible : étude de pratique professionnelle dans la région Centre Val de Loire

ObjectivesTo date, oral contraceptives remain the most frequently prescribed contraceptive method. New combined oral contraceptive (COC) regimens (continued, extended or flexible) were developed to try and space out or avoid withdrawal bleedings in order to meet women's expectations and improve their quality of life. However, there is no recommendation published regarding the management of the prescription. The purpose of our study was to describe provider's prescription habits when it comes to new COC regimens. MethodsThis is a descriptive observational study. A questionnaire was sent to gynecologists, general practitioners and midwives employed or in training in the Centre Valde Loire region. Prescription habits and knowledge about new oral contraceptive regimens were evaluated. Results83% of health professionals frequently prescribed new COC regimens. Most frequent indications were endometriosis, severe menstruation-associated symptoms, patient's desire for amenorrhea or patient's request. The extended regimen (hormone-free interval not every month) was the most frequently used. Provider's knowledge about indications and benefits of those new regimens were satisfactory. However, scientific societies guidelines were poorly acquired. ConclusionsNew COC regimens are frequently proposed by health care professionals with large variability in terms of prescription model. Along with reinforcement of COC prescription guidelines for healthcare professionals, further researches are needed to better understand differences in tolerability and acceptability in terms of quality of life of the several potential regimens.

Event-Related Potentials in Women on the Pill: Neural Correlates of Positive and Erotic Stimulus Processing in Oral Contraceptive Users.

Background/Aims: Exposure toward positive emotional cues with – and without – reproductive significance plays a crucial role in daily life and regarding well-being as well as mental health. While possible adverse effects of oral contraceptive (OC) use on female mental and sexual health are widely discussed, neural processing of positive emotional stimuli has not been systematically investigated in association with OC use. Considering reported effects on mood, well-being and sexual function, and proposed associations with depression, it was hypothesized that OC users showed reduced neural reactivity toward positive and erotic emotional stimuli during early as well as later stages of emotional processing and also rated these stimuli as less pleasant and less arousing compared to naturally cycling (NC) women.Method: Sixty-two female subjects (29 NC and 33 OC) were assessed at three time points across the natural menstrual cycle and corresponding time points of the OC regimen. Early (early posterior negativity, EPN) and late (late positive potential, LPP) event-related potentials in reaction to positive, erotic and neutral stimuli were collected during an Emotional Picture Stroop Paradigm (EPSP). At each appointment, subjects provided saliva samples for analysis of gonadal steroid concentration. Valence and arousal ratings were collected at the last appointment.Results: Oral contraceptive users had significantly lower endogenous estradiol and progesterone concentrations compared to NC women. No significant group differences in either subjective stimulus evaluations or neural reactivity toward positive and erotic emotional stimuli were observed. For the OC group, LPP amplitudes in reaction to erotic vs. neutral pictures differed significantly between measurement times across the OC regimen.Discussion: In this study, no evidence regarding alterations of neural reactivity toward positive and erotic stimuli in OC users compared to NC was found. Possible confounding factors and lines for future research are elaborated and discussed.

Assessment of Quality of Life, Sexual Quality of Life, and Pain Symptoms in Deep Infiltrating Endometriosis Patients With or Without Associated Adenomyosis and the Influence of a Flexible Extended Combined Oral Contraceptive Regimen: Results of a Prospective, Observational Study

The quality of life of women with deep infiltrating endometriosis (DIE) is impaired and may improve with combined oral contraceptives (COCs). To compare the overall and sexual quality of life of patients diagnosed with DIE with or without associated adenomyosis (AD) with that of healthy controls and determine the influence of a COC containing 2 mg dienogest/30 μg ethinyl estradiol on these aspects. We enrolled 42 women diagnosed with DIE; 31 diagnosed with DIE + AD by transvaginal ultrasound, and 39 non-AD/DIE controls. All patients were interviewed regarding pain symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), heavy menstrual bleeding using the Pictorial Blood Loss Assessment Chart, quality of life using the Short Form-36 questionnaire (SF-36), and sexual quality of life using the Sexual Quality of Life-Female questionnaire (SQOL-F) and the Brief Profile of Female Sexual Function (B-PFSF) before starting COCs and after 12 months of treatment. There was significant improvement in overall and sexual quality of life after treatment in DIE and DIE + AD patients. Non-AD/DIE controls showed significantly higher scores in the B-PFSF, the SQOL-F and the SF-36 questionnaires (P < .05) at baseline versus the other groups. DIE + AD patients showed poorer quality of sexual life and greater intensity in pain symptoms compared with DIE patients. After 12 months of treatment, there was a significant improvement in overall and sexual quality of life in the DIE and DIE + AD groups, with improvement in sexual quality of life being slightly greater in DIE + AD patients compared with DIE patients. Pain symptoms also decreased in both groups. Patients with DIE + AD showed greater impairment in overall and sexual quality of life compared with patients with isolated DIE which seems to improve with a COC containing 2 mg dienogest/30 μg ethinyl estradiol. Strengths include the long-term follow up, assessment of the impact of two associated conditions, and administration of the same COC in all patients. Limitations include the relatively small sample size, and the fact that we did not assess the effectiveness of a flexible extended COC regimen containing 2 mg dienogest/30 μg ethinyl estradiol since the groups were different at baseline. Patients diagnosed with DIE with or without AD have a decreased quality of life which may improve with a COC containing 2 mg dienogest/30 μg ethinyl estradiol. Further research is needed to confirm our results.

Abstract P173: The Impact Of Cigarette Smoking-oral Contraceptive Combination On Cardiac Remodeling In Premenopausal Female Mice

Introduction: Tobacco smoke is a major risk factor for coronary artery diseases (CAD) and chronic tobacco smoking (CS) increase the risk of CAD by 2 to 4 folds. CS effect on cardiac homeostasis has never been evaluated in premenopausal females taking oral contraceptive (OC). This study investigates CS effect on cardiac remodeling in female mice in the presence or absence of Ethinyl Estradiol (EE). Methods: Blood pressure and echocardiography were recorded for female C57BL/6J mice on EE, EE-CS, vehicle, and vehicle-CS at baseline and after 8-weeks of exposure. Cardiac inflammatory cytokines and oxidative stress markers were evaluated by real time PCR and western blots. Interstitial collagen deposition was assessed by Masson Trichrome staining. Results: Eight weeks of EE-CS treated mice showed no effect on BP but significant adverse structural and functional cardiac effects, represented by increased systolic (0.981 ± 0.035 N=11 (p&lt;0.0332)) and diastolic (1.450 ± 0.037 N=11 (p&lt;0.0002)) areas when compared to the vehicle and EE groups, along with increased systolic (1.981 ± 0.109 N=11 (p&lt;0.033)) and diastolic ( 3.911 ± 0.159 N=11 (p&lt;0.033)) volumes when compared to all groups. Functional changes were accompanied with a decreased fractional shortening (9.194 ± 1.006 N=11 (p&lt;0.033)) when compared to vehicle and EE groups with no changes in ejection fraction parameter. Moreover EE-CS treatment significantly increased NOX-4 expression (2.297 ± 0.643 N=5 (p&lt;0.033)) when compared to EE treatment alone, along with an increased pro-inflammatory profile including IL-1β (0.750 ±0.171N=5 (p&lt;0.033)) and IL-4 (4.110 ± 0.623 N= 5 (p&lt;0.002)) when compared to all groups, and IL-6 (3.045±0.910 N=5 (p&lt;0.002)) and IL-13 (2.686 ± 0.648 N=5 (p&lt;0.033)) when compared to vehicle-CS group. Morphologically, EE-CS exhibited a significant increase in interstitial fibrosis (1.186± 0.020 N=5, 3.2285 ± 0.683 N=5, (p&lt;0.033)) when compared to the vehicle-CS group. Conclusion: This study provides clear evidence that CS-exposed premenopausal female mice on OC regimen exhibited significant adverse cardiac events that could be classified under cardiac dysfunction with preserved ejection fraction. Additional experiments are warranted to further elaborate on these findings.

VP62.02: Evaluation of sonographic changes after one year of combined oral contraceptive continuous regimens in endometriosis patients

VP62.02: Evaluation of sonographic changes after one year of combined oral contraceptive continuous regimens in endometriosis patients

Cross-sectional evaluation of the impact of information on flexible extended regimens of oral contraceptives in the choices made by women seeking contraceptive counselling: the FLEXO study

Objective: Oral combined hormonal contraceptives (CHCs) are available that limit the number of menses when used in a flexible extended regimen. Our aim was to investigate the decision-making processes of women presented with a flexible extended CHC option.Methods: The FLEXO study is an epidemiological, cross-sectional, multicentre study conducted under typical clinical practice conditions to determine women’s acceptance of a flexible continuous CHC regimen versus a cyclical 21/7 day regimen, after receiving standardised information during contraceptive counselling.Results: A total of 1350 women were invited to participate, of whom 1156 were enrolled. Of these, 47.2% chose the flexible extended CHC regimen. Their main reason for choosing this regimen was to reduce the number of menses (25.7%), followed by the desire to avoid symptoms related to menstruation (21.6%). The reasons given for rejecting this regimen were the desire to have monthly menstrual cycles (24.9%) and the fear of becoming pregnant and not being aware of it due to the absence of menstruation (18.1%).Conclusion: Many women chose the extended flexible regimen when they received information about this option. Women primarily chose this pattern to relieve or eliminate discomfort related to menstruation.

Use of Oral Contraceptives to Manipulate Menstruation in Young, Physically Active Women.

Menstruation and menstrual symptoms are commonly cited barriers to physical activity in women. The delay or avoidance of menstruation through extended oral-contraceptive (OC) regimens may mitigate these barriers, yet information on menstrual-manipulation practices in young physically active women is sparse. The objective of this study was to investigate prevalence of, and reasons for, menstrual manipulation with OCs in recreationally and competitively active women. One hundred ninety-one recreationally active (self-reported moderate to vigorous physical activity 150-300min/wk) women (age 23 ± 5y), 160 subelite recreationally active (self-reported moderate to vigorous physical activity >300min/wk) women (age 23 ± 5y), and 108 competitive (state-, national- or international-level) female athletes (age 23 ± 4y) completed a self-administered questionnaire assessing OC-regimen habits and reasons for manipulation of menstruation. The majority (74%) of OC users reported having deliberately manipulated menstruation at least once during the previous year, with 29% reporting having done so at least 4 times. Prevalence of menstrual manipulation (at least once in the previous year) was not different between competitive athletes, subelite recreationally active women, and recreationally active women (77% vs 74% vs 72%; P > .05). The most cited reasons for manipulating menstruation were special events or holidays (rated by 75% as important/very important), convenience (54%), and sport competition (54%). Menstrual manipulation through extended OC regimens is common practice in recreationally and competitively active young women, for a range of reasons relating to convenience that are not limited to physical activity. This strategy may help reduce hormone-related barriers to exercise participation, thereby positively affecting participation and performance.

Cortisol reactivity and emotional memory after psychosocial stress in oral contraceptive users.

Oral contraceptive (OC) users typically show a blunted or no cortisol response to psychosocial stress. Although most OC regimens include both an inactive (dummy) and active pill phase, studies have not systematically investigated cortisol responses during these pill phases. Further, high levels of cortisol following a stressor diminish retrieval of emotional material, but the effects of stress on memory among OC users are poorly understood. We examined the effects of a psychosocial stressor, the Trier Social Stress Test, vs. a control condition on cortisol responsivity and emotional memory retrieval in women tested either during their active (n = 18) or inactive pill phase (n = 21). In secondary analyses, we quantitatively compared OC users with normally cycling women and showed a significant lack of cortisol response during both active and inactive pill phase. Emotional recall did not differ between active and inactive pill phases. Stress differentially diminished recall of negative words compared with positive or neutral words, but cortisol levels were unrelated to memory performance. These findings indicate that OC users have distinct cortisol and memory responses to stress that are similar between the active and inactive pill phases. © 2016 Wiley Periodicals, Inc.

An observational study of adherence to combined oral contraceptive regimens

Objective: To analyze adherence to an oral contraceptive (OC) regimen and correlate results to participants’ socio-demographic and behavioral characteristics.Methods: Women were prospectively enrolled and followed for 6 months. At enrollment, subjects were given a card for recording daily pill intake; its completion was checked at 6 months when women completed a self-administered questionnaire.Results: Out of 755 eligible subjects, 704 agreed to participate; 402 women completed 6 months of recording of use of an OC and properly filled the questionnaire. Good adherence was reported by 64% of participants; 20.9% missed one pill and 14.9% missed more than one pill. Mean number of missed pills per subject was 0.59 and mean number of pills delayed for less than 24 h was 1.18. Best adherence to a COC regimen was associated with evening time intake (p = 0.0019). No statistically significant associations of adherence with socio-demographic characteristics were found. Age was only marginally associated with having missed at least one pill.Conclusion: In the present study, a lower number of missed pills were observed than previously reported, but the proportion of missed pills was similar. No association with specific subject characteristics that could serve as markers of increased risk of nonadherence was found.

Creativity and individuality in matters of hormonal contraception

The relevance of the discussion about therapeutic and preventive effects of combined oral contraceptives is caused to the fact that their impact is quite often the primary motivation for the appointment and intake the drugs. “Therapeutic portrait” of the hormonal contraceptive is mainly determined by component of progestin. Knowledge and ability to use the variety of pharmacological effects, metabolic characteristics of progestins and application regimens of combined oral contraceptives allows to achieve the maximum benefit from the appointment of the drug and increases the number of adherents of hormonal contraception among patients and doctors. The authors reveal the possibility of a creative approach to the appointment of combined oral contraceptives on the example of the combination of 30 mcg of ethinyl estradiol and 2 mg of dienogest, which unites the positive properties of 19-nor progestins and progesterone derivatives. A feature of dienogest is high selectivity for the progesterone receptors, absence of estrogenic, anti-estrogenic and androgenic properties, metabolic neutrality, slight suppression of gonadotropin secretion, pronounced anti-proliferative effect on the endometrium. This allows to recommend the preparation containing 2 mg of dienogest and 30 mcg of ethinyl estradiol for contraception of conditionally healthy women during the whole reproductive period, without fear to cause hormonal or metabolic disorders, weight gain, decrease of libido. Non-contraceptive benefits of this combination make it preferable for women who suffer from dysmenorrhea, endometriosis, acne, chronic abnormal uterine bleedings. The decision to choose one or another of drugs is taken individually in each case, taking in attention the severity of clinical manifestations, concomitant somatic and gynecological pathology, previous experience and expectations of patients. However, great importance in the formation of adherence to therapy, particularly in respect of long-term use of schemes, has a price of hormonal contraceptive. The absence of any significant differences in the profiles of the solubility and bioavailability of the generic zhastinda (Alvogen) and original drug allows to reckon them as bioequivalent and makes dienogest in combination with ethinyl estradiol the most available drug for the consumer.

Hemostatic effects of two desogestrel-containing combined oral contraceptive regimens: a multinational, multicenter, randomized, open-label study

Purpose of investigation: To compare the effects of desogestrel (DSG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 21 days followed by either seven days of EE ten mcg (21/7-active) or no treatment (DSG/EE+no Tx) on hemostatic markers. Materials and Methods: This was a randomized, multicenter, open-label study that enrolled healthy premenopausal women. Non-inferiority of 21/7-active to DSG/EE+no Tx was determined if the upper limit of the two-sided 95% CI of the mean treatment difference in prothrombin fragment 1+2 (F1+2) over 24 weeks between groups was Results: 246 subjects (n=125, 21/7-active; n=121, DSG/EE+no Tx) comprised the primary analysis. Mean F1+2 levels increased in both 21/7-active and DSG/EE+no Tx regimens (least square [LS] mean changes +45 pmol/L and +56.8 pmol/L, respectively). LS mean treatment difference was -11.8 pmol/L (95% CI: -54.8, 31.2). Conclusion: The effect of adding EE ten mcg to the seven-day hormone-free interval of DSG/EE on F1+2 levels was non-inferior to traditional DSG/EE.

Cardiovascular risks associated with the use of drospirenone-containing combined oral contraceptives

ObjectivesThe “Long-term Active Surveillance Study for Oral Contraceptives” investigated the risks of long-term use of a 21-day regimen of drospirenone and ethinylestradiol (DRSP) compared to established oral contraceptives (OCs) in a routine clinical setting. Study designProspective, controlled, non-interventional cohort study conducted in seven European countries with three main exposure groups: new users of DRSP, levonorgestrel-containing OCs (LNG), and OCs containing other progestogens (Other OCs). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular cardiovascular events. Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models. ResultsA total of 1,113 study centers enrolled 59,510 women. Overall 28%, 26% and 45% of these women used DRSP, LNG and Other OCs, respectively. Study participants were followed for up to ten years (mean value, 5.4years), which generated 318,784 woman-years (WY) of observation. Low loss to follow-up and drop-out rates of 2.9% and 16.8% were achieved. DRSP, LNG, and Other OCs showed similar incidence rates of venous thromboembolism. Corresponding hazard ratios (HRs) were close to unity. For arterial thromboembolic events (ATE) and initiation of antihypertensive treatment statistically significant lower risks were found for DRSP compared to LNG and Other OCs. ConclusionDRSP use was associated with similar general health risks and a low risk of ATE compared to OCs containing other progestogens. Implication statementThe 21-day regimen of drospirenone-containing combined oral contraceptives is associated with similar risk of VTE compared to other combined oral contraceptives as well as potentially with a lower risk of ATE.

Short-Term Treatment of Bothersome Bleeding for Etonogestrel Implant Users Using a 14-Day Oral Contraceptive Pill Regimen

The etonogestrel contraceptive implant is one of the most effective contraceptives available, with a failure rate of 0.05%. Approved for 3 years of use, it has a high 2-year continuation rate (53%–90%). Up to 11.3% of women in clinical trials discontinued use of this implant before 3 years because of bothersome bleeding (prolonged bleeding and frequent episodes). This double-blind randomized, placebo-controlled trial was designed to determine whether 14 days of treatment with a combination of oral contraceptive pills (OCPs) would stop bleeding in users of the implant with bothersome bleeding. The OCP regimen was a low-dose combination of levonorgestrel and ethinyl estradiol. The primary study outcome was the proportion of women in each group who stopped bleeding during treatment and continued to report no bleeding at the end of 14 days of therapy. Prespecified secondary outcomes included number of days until temporary cessation of bleeding, number of days without bleeding during therapy, and number of days to recurrence of bleeding after therapy was discontinued. The investigators hypothesized that the intervention would result in temporary interruption of bleeding in 80% of the treatment group compared with 20% in the control group; using 80% power, a sample size of 26 women (13 in each group) was required. The study was performed according to the intention-to-treat principle. Most subjects (78%) were young white women. Baseline characteristics of groups were similar. Mean age was 21 to 22 years (range, 18–44 years). A total of 66 women were screened between November 2013 and December 2014; 32 of these were randomized to an OCP group or to a placebo group. Users of the etonogestrel implant with bothersome bleeding episodes for at least 7 consecutive days were randomized to receive 14 pills of combined OCPs (150 μg levonorgestrel and 30 μg ethinyl estradiol, n = 16, or an identical-appearing placebo, n = 16). Significantly, more women in the OCP group than in the placebo group were likely to have a temporary interruption of bleeding during the study period (14 of 16 [87.5% ± 16.2%] in the OCP group vs 6 of 16 [37.5% ± 23.7%] in the placebo group); the odds ratio was 11.7, with a 95% confidence interval of 1.9 to 70.2 (P < 0.01). Among women who had a temporary interruption of bleeding during OCP therapy, 85.7% had bleeding recurrence within 10 days after treatment ended. Use of a low-dose combination OCP in etonogestrel implant users who had reported bothersome bleeding before treatment usually stops bleeding within 14 days. However, bleeding resumes in most patients within 10 days of treatment cessation.

Ovulatory effects of three oral contraceptive regimens: a randomized, open-label, descriptive trial

ObjectiveThis study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive (COC) regimen that included only ethinyl estradiol (EE) during the traditional hormone-free interval (HFI) and two commercially available 28-day regimens, a 24/4 and a 21/7 regimen. Study designThe randomized, open-label, parallel-group descriptive study was conducted at two US sites. Healthy, reproductive-aged women (n=146) were randomized to one of three groups for three consecutive 28-day cycles, as follows: treatment 1 (n=39 completed): 21/7-active COC [21days of 150 mcg desogestrel (DSG)/20 mcg EE, followed by 7days of 10 mcg EE (DSG/EE+7days EE)], treatment 2 (n=39 completed): 24days of 3mg drospirenone (DRSP)/20 mcg EE, followed by 4 placebo (PBO)-pill days (DRSP/EE+4days PBO) and treatment 3 (n=42 completed): 21days of 100 mcg levonorgestrel (LNG)/20 mcg EE, followed by 7 PBO-pill days (LNG/EE+7days PBO). The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogland and Skouby (H/S) method. ResultsOvarian activity rate (H/S grade 4 or 5) was low for all three treatments: 0% [95% confidence interval (CI) 0–2.8] for DSG/EE+7days EE, 1% (95% CI 0.2–5.2) for DRSP/EE+4days PBO and 1% (95% CI 0–3.9) for LNG/EE+7days PBO. All three treatments showed similar suppression of serum progesterone, 17β-estradiol, follicle-stimulating hormone and luteinizing hormone levels. ConclusionsThe 21/7-active low-dose COC regimen (DSG/EE+7days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4days PBO) and 21/7 (LNG/EE+7days PBO) regimens. ImplicationsThe 21/7-active low-dose COC regimen (DSG/EE+7days EE) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 (DRSP/EE+4days PBO) and the 21/7 (LNG/EE+7days PBO) comparator regimens.

Migraine et contraception

Migraine is a common pathology in women. Migraine disease is well defined by the International Headache Society and has to be distinguished from others types of headaches. The occurrence of migraine attacks is frequently linked to the menstrual cycle. Many studies have related a connexion with hormonal fluctuations and migraine event. Migraine with aura is currently identified as a stroke risk factor and this risk dramatically increases in case of oestroprogestative pill intake and smoking. The World Health Organization established guidelines about oestroprogestative intake in case of migraine while strictly contraindicating oestroprogestative intake in patients with migraine with aura. This review explains the influence of different contraceptive intake, oral contraceptive regimens, and type of oestrogen in oestroprogestative contraceptive on migraine occurrence.

Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy

ObjectivePharmacokinetics of norethindrone in combination oral contraceptive regimen are well described among HIV+ women treated with ritonavir-boosted protease inhibitor therapies; however, such characterization is lacking in women using progestin-only contraception. Our objective is to characterize pharmacokinetics of norethindrone in HIV+ women using ritonavir-boosted atazanavir treatment during progestin-only contraceptive regimens. Study designAn open-label, prospective, nonrandomized trial to characterize the pharmacokinetics of norethindrone in HIV+ women receiving ritonavir-boosted atazanavir (n=10; treatment group) and other antiretroviral therapy known to not alter norethindrone levels (n=17; control group) was conducted. Following informed consent, women were instructed to take a single daily fixed oral dose of 0.35 mg norethindrone and 300 mg/100 mg atazanavir/ritonavir for 22 days. On day 22, serial blood samples were collected by venous catheter at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h. Whole blood was processed to collect serum and stored at −20°C until later analysis using radioimmunoassay. Pharmacokinetic parameters were estimated using noncompartmental method. ResultsIn the treatment group, compared to the control group, an increase in area under the curve0–24 (16.69 h*ng/mL vs. 25.20 h*ng/mL; p<.05) and maximum serum concentration (2.09 ng/mL vs. 3.19 ng/mL; p<.05), decrease (25%–40%) in apparent volume of distribution and apparent clearance, and unaltered half-life were observed. Conclusion(s)Our findings suggest that progestin-only contraceptives, unlike combination oral contraceptives, benefit from drug–drug interaction and achieve higher levels of exposure. Further studies are needed to establish whether pharmacokinetic interaction leads to favorable clinical outcomes. ImplicationsNorethindrone-based progestin-only contraceptives, unlike combination oral contraceptives, exhibit greater drug exposure when co-administered with ritonavir-boosted atazanavir regimen and thus may not warrant a category 3 designation by the World Health Organization. Prospective studies are needed to confirm whether pharmacokinetic interaction results in favorable clinical outcomes.

Metabolic Profiles in Phase 2 Study of Two 21/7 Oral Contraceptive Regimens (±7 Hormone-Free Days)

INTRODUCTION: Metabolic changes observed in women taking combined oral contraceptives may vary depending on the dose and regimen of the combined oral contraceptive components. METHODS: We compared metabolic profiles (secondary endpoints) in women enrolled in a multinational randomized parallel-group open-label study comparing a 21-day combined oral contraceptive regimen containing 150 micrograms desogestrel and 20 micrograms ethinyl estradiol followed by 7 days of 10 micrograms of ethinyl estradiol (Lecette; Treatment 1) compared with a traditional combined oral contraceptive with 7 no treatment (hormone-free) days (Treatment 2). Healthy women aged 18-40 years with regular menstrual cycles and no contraindications to estrogens progestins or both received one of the two combined oral contraceptive regimens for six consecutive 28-day cycles. Serum total cortisol cortisol-binding globulin thyroid-stimulating hormone and sex hormone-binding globulin were measured at baseline and weeks 11 and 23. RESULTS: Of 293 women randomized 246 comprised the per-protocol population (Treatment 1: n=125; Treatment 2: n=121). Mean baseline metabolic parameters were similar for both groups. Increases in mean total cortisol cortisol-binding globulin and sex hormone-binding globulin evident by week 11 were similar with both combined oral contraceptives through week 23. Overall least square mean changes+/-standard errors for Treatments 1 and 2 were 239.0+/-15.7 and 230.8+/-16.0 nmol/L respectively for total cortisol (P=.71) and 40.8+/-1.6 and 37.2+/-1.6 mg/L for cortisol-binding globulin (P=.11); overall sex hormone-binding globulin rose by 163.4+/-7.3 and 149.1+/-7.5 nmol/L (P=.17). Neither group had clinically relevant changes in thyroid-stimulating hormone. CONCLUSIONS: Observed total cortisol cortisol-binding globulin and sex hormone-binding globulin increases in women taking a 21/7 combined oral contraceptive regimen followed by either 7 days of 10 micrograms ethinyl estradiol or 7 hormone-free days were similar.