Hormone-free Interval Research Articles

Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study

To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in Japanese patients with endometriosis. A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 162 Japanese women diagnosed with endometriosis. Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 15 mg and DRSP 3 mg daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a one-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period. Changes in visual analog scale scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period. E4/DRSP showed changes in average visual analog scale scores for the most severe pelvic pain (-33.2 mm) from baseline to the end of the six-cycle treatment. The between-group difference was significant (-8.5 mm, two-sided 95% confidence interval: -16.1 to -0.9 mm), showing superiority to placebo (p=0.028). Responder rates, ≥30% and ≥50% reduction in visual analog scale scores from baseline, were larger in the E4/DRSP group than in the placebo group: 53.2% versus 29.6% (p=0.004) and 36.4% versus 12.3% (p<0.001). Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. E4/DRSP reduced the size of endometriomas and improved quality of life, based on quality of life-related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups. E4/DRSP effectively treats endometriosis-associated pain and improves gynecological findings. E4/DRSP may be a safe, new option for endometriosis treatment with a potentially reduced risk of thromboembolic events.

PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study

BackgroundEndogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology.MethodsThis analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7–14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit.ResultsThe study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 – 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 – 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 – 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 – 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval.ConclusionSystemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.

The Cycle study: a prospective study on cholesterol levels during the menstrual cycle

Abstract Background Previous studies showed fluctuating lipid levels during the menstrual cycle in healthy women with normal cholesterol (nChol). Cycle-related variations in lipid levels in women with familial hypercholesterolemia (FH) have not been studied, while these might have important consequences for lipid management. Purpose To investigate menstrual cycle-related fluctuations in lipid levels in women with FH compared to those with nChol. Methods In the Netherlands and Norway, 20 women with clinical/genetic FH and 63 healthy women with nChol were included - details are presented in the figures. Participants had to have a regular cycle between 21-35 days, while pregnant women, and those using hormone-based contraceptives without hormone free interval (HFI) were excluded. Lipid levels were measured in the follicular (visit 1), ovulation (visit 2), and luteal (visit 3) phases. In women using oral contraceptives (OC) measurements were taken during day 12-14 of the pill period (visit 1) and during day 5-7 of the HFI (visit 2). Results Mean (sd) age of the included subjects was 33 (9) years, BMI 23.9 (4) kg/m2, and cycle duration 28 (2) days. These characteristics were similar in FH and nChol. Women with nChol showed slight, although statistically significant, cycle-related variations in cholesterol levels (mean maximum variation total Chol 0.53, LDL-Chol 0.39 and HDL-Chol 0.22 mmol/L; figure 1). FH women who did not receive statin therapy for various reasons showed largest mean variations (total Chol 0.80, LDL-Chol 0.59 and HDL-Chol 0.23 mmol/L), with the highest lipid levels during the ovulation phase. The women with OC had an increase in total- and LDL-cholesterol (groups combined: mean difference 0.55 and 0.51 mmol/L, respectively) between the two visits (n=9) (figure 2). Conclusions In women with untreated FH and normal cholesterol with a regular menstrual cycle, total- and HDL-cholesterol were highest at ovulation. These menstrual fluctuations were absent in women with FH who used statins. Women with OC showed an increase in total- and LDL-cholesterol from the contraceptive pill period to the HFI. Even though in most women the absolute variation in lipid levels during the menstrual cycle and OC are modest, the moment of measurement can be of clinical value in particular in women with untreated high lipid levels. In these women, it is recommended to measure lipid levels at a fixed time of the menstrual cycle.Figure 1Figure 2

A new progestin-only pill (POP): the impact of drospirenone-only pill 4 mg 24 + 4 on coagulation markers and bleeding patterns

Purpose Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control. The aim of this study was to evaluate the impact of a new POP [4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval] on some coagulation markers (both procoagulant and fibrinolytic) and to describe its impact on bleeding patterns. Materials and methods This is a prospective trial, based on serum evaluation of following coagulation markers and tests: Factor (F) X, F VIII, F V, INR, aPTT, Protein S and antithrombin III. A ‘bleeding diary’ was used to categorise women as having (1) unscheduled bleeding, (2) scheduled bleeding and (3) amenorrhoea. Thirty patients were followed for six 28-day intake cycles, with a follow-up at the end of the 3rd and 6th cycles. Results There was a significant decrease of F X (p = 0.03) (-5.7% at cycle 6). No significant changes have been observed for F VII, F V and INR. A significant increase in aPTT (p = 0.01 at 3 cycles), Protein S (p = 0.0006 at 3 cycles) and antithrombin III (p < 0.0001 at 3 cycles) was recorded. This non-deteriorating coagulation impact was associated with a significant and progressive reduction of days of scheduled and unscheduled bleeding in users between cycles 4 and 6 (from 1.3 ± 0.2 days at cycle 4 to 0.8 ± 0.1 days at cycle 6 and from 2.6 ± 0.4 days at cycle 4 to 0.6 ± 0.2 days at cycle 6, respectively, p < 0.0001). Conclusions DRSP 24 + 4 use was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Preservation of the reproductive health of military women: global experience and realities of Ukraine

A review of world literature and Ukrainian researches on the most common requests to gynecologists among military women, on the structure of pathology and treatment methods was made. Special attention is paid to the hormonal contraception, namely combined oral contraceptives (COCs) in the usual and continuous regime (avoiding the hormone-free interval) and the levonorgestrel-releasing intrauterine systems (LNG-IUDs).Cases of global practice of using COCs in extended regimen were considered, which showed that 47.2% of 1156 women chose a prolonged regimen of COCs, the main reason for this was the desire to avoid symptoms associated with menstruation. We consider this option very positive for military women, because some studies show that military women who took COCs in a continuous regimen were almost twice as favorable to their reception as those who used them in a regular mode.The positive aspects of the LNG-IUDs use in military women are presented, as a factor in the prevention of abnormal uterine bleeding, reducing the risk of iron deficiency in case of possible blood loss, and reducing the intensity of dysmenorrhea as a negative factor in the military conditions.Ways to increase compliance between a gynecologist and a military woman are also considered, using the example of global studies, which prove that insufficient awareness of patients about the possible ways and positive effects of using COCs in extended regimen reduced patients’ commitment to choosing new regimens.Conclusions. In today’s realities, the gynecological service in our country faces a number of new problems that require a strategic approach and solution. World practice and national studies prove that stress-induced hormonal disorders in military women, such as abnormal uterine bleeding, menstrual cycle disorders, dysmenorrhea, are negative factors in combat conditions, require the attention and resolution by doctors. One of the options for solving this problem can be the appointment of COCs according to the usual and extended scheme or appointment of LNG-IUDs.

Changes in Visual Long-Term Potentiation Show Preserved Cyclicity in Human Females Taking Combined Oral Contraceptives

Introduction: The combined oral contraceptive (COC) pill is often employed to address physical and neurological symptoms in menstrual cycle-related disorders by suppressing shifts in endogenous gonadal hormone fluctuations. Symptom persistence, especially in the lead up to the hormone-free interval (HFI), suggests an underlying neurobiological mechanism of preserved cycling. Our study utilised a non-invasive method of visually inducing long-term potentiation (LTP) to index changes in neural plasticity in the absence of hormonal fluctuations. Methods: Visually induced LTP was recorded using electroencephalography in 24 healthy female COC users across three sessions: days 3 and 21 during active hormone pills, and day 24 during the HFI. The Daily Record of the Severity of Problems (DRSP) questionnaire tracked premenstrual symptoms. Dynamic causal modelling (DCM) was used to elucidate the neural connectivity and receptor activity changes associated with LTP across different days of COC. Results: Visually induced LTP was greater on day 21 than day 3 (p = 0.011) and was localised to the P2 visually evoked potential. There was no effect of the HFI (day 24) on LTP. DCM of differences between days 3 and 21 showed changes to inhibitory interneuronal gating of LTP in cortical layer VI. The DRSP only showed a significant increase in symptoms in the HFI, meaning the LTP result appeared more sensitive to cyclicity. Conclusions: This study provides objective evidence of preserved cyclicity in COC users through enhanced LTP on day 21 compared to day 3 of a 28-day COC regimen, indicating that relatively higher excitation in the brain despite peripheral gonadal suppression may underlie and exacerbate menstrual cycle-related disorders.

Sex Hormones and Calcitonin Gene-Related Peptide in Women With Migraine: A Cross-sectional, Matched Cohort Study.

Sex hormones may modulate calcitonin gene-related peptide (CGRP) release in the trigeminovascular system. We studied CGRP concentrations in plasma and tear fluid in female participants with episodic migraine (EM) and a regular menstrual cycle (RMC), female participants with EM and combined oral contraception (COC), and female participants with EM in the postmenopause. For control, we analyzed 3 corresponding groups of age-matched female participants without EM. Participants with an RMC had 2 visits: during menstruation on menstrual cycle day 2 ± 2 and in the periovulatory period on day 13 ± 2. Participants with COC were examined at day 4 ± 2 of the hormone-free interval (HFI) and between days 7 and 14 of hormone intake (HI). Postmenopausal participants were assessed once at a random time point. Plasma and tear fluid samples were collected at each visit for determination of CGRP levels with an ELISA. A total of 180 female participants (n = 30 per group) completed the study. Participants with migraine and an RMC showed statistically significantly higher CGRP concentrations in plasma and tear fluid during menstruation compared with female participants without migraine (plasma: 5.95 pg/mL [IQR 4.37-10.44] vs 4.61 pg/mL [IQR 2.83-6.92], p = 0.020 [Mann-Whitney U test]; tear fluid: 1.20 ng/mL [IQR 0.36-2.52] vs 0.4 ng/mL [IQR 0.14-1.22], p = 0.005 [Mann-Whitney U test]). In contrast, female participants with COC and in the postmenopause had similar CGRP levels in the migraine and the control groups. In migraine participants with an RMC, tear fluid but not plasma CGRP concentrations during menstruation were statistically significantly higher compared with migraine participants under COC (p = 0.015 vs HFI and p = 0.029 vs HI, Mann-Whitney U test). Different sex hormone profiles may influence CGRP concentrations in people, with current or past capacity to menstruate, with migraine. Measurement of CGRP in tear fluid was feasible and warrants further investigation.

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.

OPTITMIZATION OF MANAGEMENT TACTICS FOR PATIENTS WITH HEADACHE CAUSED BY ESTROGEN WITHDRAWAL

Abstract. The clinical case of a patient who applied for an appointment regarding the selection of a method of contraception after a medical abortion was studied. Anamnetically, the patient had symptoms caused by the withdrawal of estrogens when taking combined oral contraceptives (COCs) and also with a physiological decrease in the level of estrogens during the menstrual cycle without the use of combined oral contraceptives. After consulting a neurologist, a migraine-like disorder was diagnosed as a "Headache caused by the withdrawal of estrogens", and a gynecologist's consultation was recommended to choose a method of contraception that does not give this complication. The study of this clinical case demonstrated the possibility of optimizing the management tactics of patients with headache caused by the withdrawal of estroneens by using the drug claira for contraception. This drug has a dynamic dosing regimen, which provides for a gradual decrease in the estrogenic component in combination with a gradual increase in the dosage of progestin and a subsequent short hormone-free interval (BGI), lasting only two days. An additional advantage is that a short BGI helps to maintain a stable level of estradiol and inhibits the development of follicles. This drug, having high contraceptive reliability, has also demonstrated high effectiveness in the occurrence of headaches caused by estrogen deficiency. Keywords. Headache, estrogen deficiency, clair, combined oral contraceptives.

Comparison of two drospirenone-containing oral contraceptives for their effect on the ovary, menstrual cycle, acne, and side-effect profile: 20 µg ethinylestradiol/3 mg drospirenone (24/4) versus 30 µg ethinylestradiol/3 mg drospirenone (21/7)

Background/Aim: Serious side effects, depending on the length of the hormone-free interval and the estrogen dose, cause the discontinuation of combined oral contraceptives (COCs). Therefore, it is important to identify COCs with minimal side effects which provide effective contraception. This study aimed to compare the effects of two different drospirenone-containing oral contraceptives (COCs) on ovarian suppression, cycle control, premenstrual symptoms, pain, acne, and the incidence of side-effects. Methods: This prospective randomized controlled study was conducted with eighty women aged between 17-40 years. Patients were randomized to either 3mg drospirenone/30mcg ethinylestradiol (21/7 tablets) (Group 1) or 3mg drospirenone/20mcg ethinylestradiol (24/4 tablets) (Group 2) COCs. On Day-3 of the pre-treatment cycle, menstrual cycle patterns, serum hormone and lipid levels, menstrual complaints were recorded, followed by an evaluation of Day-21 progesterone levels, sonographic evaluation of endometrial thickness and the ovaries. Same assessment was repeated after pill use and the findings of the two cycles were compared. Results: Both COC formulations suppressed serum hormone levels, decreased endometrial thickness and reduced incidence of dysmenorrhea-dyspareunia, and acne while serum HDL-cholesterol level was increased. Progesterone, FSH and endometrial thickness were lower, and serum cholesterol level was higher in Group 2 (P=0.007, P=0.044, P

Unintended pregnancy in users of nomegestrol acetate and 17β-oestradiol (NOMAC-E2) compared with levonorgestrel-containing combined oral contraceptives: final results from the PRO-E2 study

Objective To assess and compare the risk of unintended pregnancy in NOMAC-E2 users with levonorgestrel-containing COC (COCLNG) users in clinical practice. Study design In this observational study, new users 1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (contraceptive failures per 100 women-years [WY]), crude hazard ratios (HRcrude) and adjusted hazard ratios (HRadj). Results Overall, 44,559 and 46,754 users were recruited to the NOMAC-E2 and COCLNG user cohorts, respectively. There were 64 unintended pregnancies in NOMAC-E2 users (0.15 per 100 WY; 95% CI, 0.11–0.19) and 200 in COCLNG users (0.41 per 100 WY; 95% CI, 0.35–0.47). The unintended pregnancy risk was statistically significantly lower in the NOMAC-E2 cohort (p<.0001) compared to the COCLNG user cohort. The HRadj of NOMAC-E2 vs COCLNG was 0.45 (95% CI, 0.34–0.60; adjusted for age, body mass index, gravidity, COC user status, education level). Conclusions NOMAC-E2 demonstrated superior contraceptive effectiveness compared to COCLNG, likely due to the comparatively short hormone-free interval and possibly reinforced by the long half-life of NOMAC.

Managing the side effects of contraception

Side effects are the most common reason for the discontinuation of contraceptive methods. Dr Katie Boog summarises the available evidence on how to manage them Although often transient, side effects are the most common reason for individuals to discontinue contraception. The evidence to prove causality is limited, as is evidence-based guidance on how to manage these side effects. This article summarises the available evidence. For individuals who have new or worsening acne on progestogen-only contraception (POC), switching to combined hormonal contraception (CHC) is likely to improve their skin. Continuous or extended CHC use may be beneficial for individuals with premenstrual mood change, and for those who experience headaches in the hormone-free interval. Unpredictable bleeding patterns on POC are common. Injectable users can try reducing the interval between injections to 10 weeks. Implant, injectable or intrauterine system users can be offered a 3-month trial of a combined oral contraceptive pill (COC). CHC and POP users with unpredictable bleeding may benefit from switching to an alternative preparation.

Managing the side effects of contraception

Although often transient, side effects are the most common reason for individuals to discontinue contraception. The evidence to prove causality is limited, as is evidence-based guidance on how to manage these side effects. This article summarises the available evidence. For individuals who have new or worsening acne on progestogen-only contraception (POC), switching to combined hormonal contraception (CHC) is likely to improve their skin. Continuous or extended CHC use may be beneficial for individuals with premenstrual mood change, and for those who experience headaches in the hormone-free interval. Unpredictable bleeding patterns on POC are common. Injectable users can try reducing the interval between injections to 10 weeks. Implant, injectable or Intrauterine system users can be offered a 3-month trial of a combined oral contraceptive pill (COC). CHC and POP users with unpredictable bleeding may benefit from switching to an alternative preparation.

Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study

Many studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.

Real clinical practice and contraception for young women with children

The review presents the psychosocial characteristics of young women in todays millennial generation and survey data regarding their hormonal contraceptive requirements. The results of randomized clinical trials and real-life studies of the use of the combined oral contraceptive (COC) Qlaira containing estradiol valerate and dienogest (E2V/DNG) in a dynamic dosing regimen were analyzed, in which the reliability of the contraceptive effect of the drug was identified and confirmed, the restoration of fertility was population level after drug withdrawal, its minimal effect on metabolism and a reduced risk of cardiovascular complications (venous and arterial thrombosis) when using Qlaira COC in comparison with other COCs. The absence of a negative effect of COC E2V/DNG on body weight, sexual function and vaginal microbiocenosis in most women has been proven. The data on satisfactory characteristics of menstrual bleeding (lighter and shorter) in users of Qlaira COC and a decrease in symptoms associated with a hormone-free interval, which often occur when taking other COCs in the 21/7 regimen, are presented. The favorable efficacy and safety profile of COC E2V/DNG in real conditions, the advantages of estrogen bioidentical to the endogenous, in the composition of the drug, the dosage regimen 26/2, the positive effect on the lifestyle, determine the significant satisfaction of young women, including young women with children, and the ability to use the drug for a long time until menopause.

Migraine start, course and features over the cycle of combined hormonal contraceptive users with menstrual migraine \u2013 temporal relation to bleeding and hormone withdrawal: a prospective diary-based study

BackgroundMany studies have described the features of menstrually-related migraines (MRM) in the natural cycle and the efficacy of prevention. MRM in combined hormonal contraceptive (CHC) users has scarcely been researched. Estrogen and progestin withdrawal in CHC users are both more abrupt and from higher hormone levels compared with the natural cycle. An advantage for prevention of MRM in CHC users is that the hormone withdrawal is predictable. It is unknown, whether the attacks during the hormone-free interval are associated with the hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention.MethodsFor this prospective diary-based trial we collected migraine and bleeding data from CHC users with MRM in at least two of three cycles. We analyzed frequency of migraines over the whole CHC cycle. During the hormone-free phase the relation between onset of migraine and onset of bleeding was studied. We compared pain intensity and identified prolonged-migraine attacks during hormone use and the hormone-free phase.ResultsDuring the hormone-free interval the number of migraine days and the pain score/migraine day were significantly higher in comparison with the mean during hormone use. The prevalence of migraine attacks was fourfold on hormone-free days 3–6. Migraine typically started on days 1–4. Migraine in relation to bleeding mostly occurred on days − 1 to + 4. In 78% of the cycles the first migraine day occurred during bleeding days 1 ± 2 and 48% started on days − 1 and day 1. The predictability of the first bleeding day was very high.ConclusionThe day of hormone-withdrawal migraine and the first bleeding day are highly predictable in CHC users. Migraine onset is mostly day − 1 and 1 of the bleeding and on days 1–4 of the hormone-free interval. Migraine attacks of CHC users in the hormone-free interval are severe and long lasting. Further trials are necessary to investigate if this knowledge can be used to optimise prevention.

Drospirenone 4 mg-only pill (DOP) in 24+4 regimen: a new option for oral contraception

ABSTRACT Introduction The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties. Areas covered This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns. Expert Opinion The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea).

Contraception modes: increasing women’s commitment to modern combined oral contraceptives with the shortest possible hormone-free interval

By definition, contraception is the prevention of pregnancy and infection from diseases by mechanical, chemical and other contraceptives and methods. According to World Health Organization (WHO) statistics, up to 40% of women of reproductive age still believe that their needs for family planning services are not met during counseling. When recommending contraception, it is important to consider: the characteristics of the potential consumer, the underlying risk of the disease, possible undesirable drug reactions of various drugs, the cost, availability and preferences of the woman herself. Women are often forced to abandon the use of a contraceptive method in connection with adverse events, for example, when using combined oral contraceptives (COCs), they may feel worse (headaches, mood lability, weight gain, swelling, decreased libido) in a hormone-free interval, especially with the reception mode 21/7. Lack of contraception can lead to an increased risk of an unwanted pregnancy. According to statistics in the Russian Federation in 2018, the absolute number of abortions amounted to 567 183, which, according to the UN classification, corresponds to the average level (level of abortion rate per 1000 women of childbearing age). According to clinical practice, there is a relationship between deterioration of well-being and the duration of the hormone-free interval. At the moment, in our country there is the only COC, which has a hormone-free interval of 2 days, containing bioidentical estrogen estradiol valerate and dienogest. According to the Cochrane Library, COCs with a short hormone-free interval are most effective in relation to the clinical manifestations of the estrogen withdrawal syndrome. WHO calls on clinicians to raise womens awareness of modern methods of contraception.

Needs, expectations and doubt users of hormonal contraceptives

Description. The review is presented by modern publications, reflecting the importance of high-quality patient counseling when choosing a method of contraception and the factors that influence it. The choice of combined oral contraceptive (COC) is determined by the need for reliable and safe contraception, expectations for an improved quality of life, and doubts about the frequency of side effects and effects on reproductive and somatic health. Modern COCs containing natural hormone (estradiol valerate), a new gestagen (dienogest) with a dynamic regime and a shortened hormone-free interval (2 days) satisfy the COC requirements of most women from menarche to menopause when contraception is required. An improvement in the profile of menstrual bleeding (a decrease in blood loss in 88% of users) and sexual functioning (increased libido, arousal, and maintaining the cyclical nature of sexual behavior) has been shown. Estradiol valerate does not affect metabolism, has a low risk of thromboembolic events (the adjusted risk of venous thromboembolism compared to other COCs is 0.4) and a low frequency of failure due to side effects (1.7%). This tool is characterized by high efficiency (adjusted Pearl index 0.42) and user satisfaction (78.180.2%).&#x0D; Conclusion. COCs with estradiol valerate/dinogest in 26/2 mode, fully satisfying the requirements of women for contraception, contributes to high adherence to it, that is, consistent and correct use, which contributes to the long-term use of the selected COC and ensures the quality of life of women for many years.

Bleeding Pattern and Management of Unexpected Bleeding/Spotting with an Extended Regimen of a Combination of Ethinylestradiol 20 mcg and Drospirenone 3 mg.

ObjectiveTo compare the bleeding pattern in women using ethinylestradiol 20 mcg/drospirenone 3 mg (EE 20 mcg/DRSP 3 mg) in a 24/4-day cyclic regimen with an extended regimen. Unexpected bleeding/spotting in the extended regimen group was managed by allowing a 4-day hormone-free interval (HFI).MethodsThis was a randomized, prospective, open-label, multicenter study. Participants (N = 348) were randomized to receive EE 20 mcg/DRSP 3 mg in either an extended regimen (EE/DRSPes group) or a 24/4-day cyclic regimen (EE/DRSP24/4 group) and followed for 168 days. In the EE/DRSPes group, a 4-day HFI was allowed whenever unexpected bleeding/spotting persisted for ≥7 consecutive days. The participants assessed their bleeding daily as “no bleeding,” “spotting,” or “light,” “moderate,” or “heavy” bleeding according to a predefined scale.ResultsEE/DRSPes group experienced fewer days of bleeding than those using a 24/4 cyclic regimen (P < 0.001). After 168 days, 57.5% of women in the EE/DRSPes group achieved complete amenorrhea (i.e., neither bleeding nor spotting) and 73.9% achieved “no bleeding” (i.e., no bleeding with or without spotting) during the final 28-day interval of the study period. Women in the extended group who instituted the 4-day HFI experienced a 94.1% rate of successful management of unexpected bleeding/spotting.ConclusionThe use of EE 20 mcg/DRSP 3 mg in an extended regimen resulted in high rates of amenorrhea and “no bleeding”. Unexpected bleeding/spotting in the EE/DRSPes group could be managed effectively with a 4-day HFI.Clinical Trial RegistrationInternational Standard Randomised Controlled Trial Number (ISRCTN57661673): http://www.controlled-trials.com/isrctn/pf/57661673.