Hormone-free Interval Research Articles

Migraine Management During Menstruation and Menopause.

Migraine is most prevalent in women during their reproductive years. An understanding of the effects of menstruation and menopause on migraine can enable neurologists to provide targeted and appropriate medical and hormonal strategies, enabling their patients to achieve better control of migraine and reduced disability. This article reviews the effects of hormonal events on migraine and summarizes the evidence-based options available for management. Estrogen "withdrawal" during the late luteal phase of the natural menstrual cycle and the hormone-free interval of combined hormonal contraceptives has long been implicated in the pathophysiology of menstrual migraine. However, more recent research suggests that other independent mechanisms may be relevant. Prostaglandin inhibitors used for management of dysmenorrhea are effective for associated menstrual migraine, suggesting a common pathophysiology. The interplay between serotonin and estrogen also deserves further research. Menstrual and perimenopausal migraine can be managed effectively using a variety of strategies, the choice of which depends on the efficacy of acute treatment, predictability and regularity of menstruation, use of contraception, and presence of menstrual disorders or perimenopausal vasomotor symptoms.

Hormone withdrawal-associated symptoms with ethinylestradiol 20 μg/drospirenone 3 mg (24/4 regimen) versus ethinylestradiol 20 μg/desogestrel 150 μg (21/7 regimen).

ObjectiveTo assess whether the combined oral contraceptive (COC) ethinylestradiol (EE) 20 μg/drospirenone 3 mg taken in a 24/4-day regimen (ie, 4-day hormone-free interval) is more effective than an EE 20 μg/desogestrel (DSG) 150 μg COC taken in a 21/7-day regimen (ie, 7-day hormone-free interval) in reducing hormone withdrawal-associated symptoms (HWAS).MethodsThis double-blind, randomized study (NLM identifier: NCT01076582) was conducted at 34 centers in 12 countries. Otherwise healthy women who experienced ≥2 HWAS of headache, pelvic pain, and/or bloating when using their current COCs in a 21/7-day regimen were recruited. Subjects rated the severity of their HWAS daily on a seven-point Likert scale during a baseline cycle and during four 28-day cycles with EE/drospirenone 24/4 (n=290) or EE/DSG 21/7 (n=304). The primary variable was the mean change from baseline to cycle 4 in the composite HWAS score (sum of scores for all three symptoms) during cycle days 22–28.ResultsIn the EE/drospirenone 24/4 group, the mean (standard deviation) composite HWAS score during cycle days 22–28 was reduced from 42.2 (24.8) at baseline to 12.8 (13.4) at cycle 4 (change from baseline: −30.3 [22.9]). In the EE/DSG 21/7 group, the corresponding value was reduced from 41.9 (25.8) to 14.3 (13.2) (change from baseline: −27.7 [24.8]), not significantly different versus EE/drospirenone 24/4. Bleeding pattern, treatment response, rescue medication use, compliance, quality of life, and tolerability were similar between treatments.ConclusionBoth EE/drospirenone 24/4 and EE/DSG 21/7 reduced the composite HWAS score from baseline to cycle 4 in otherwise healthy women. The differences between treatments were too small to be statistically significant.

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.

The effect of pycnogenol on patients with dysmenorrhea using low-dose oral contraceptives.

ObjectiveMenstrual symptoms such as dysmenorrhea usually occur during the hormone-free interval in oral contraceptive users. Progestin withdrawal activates NF-κB transcription factor, which upregulates both vascular endothelial growth factor (VEGF) and Cox-2 expression in the endometrium. The use of natural NF-κB inhibitors such as pycnogenol may block this response, improving dysmenorrhea.Patients and methodsTwenty-four patients with severe dysmenorrhea were allocated to one of two treatment groups. In Group A (n=13), women were treated with an oral contraceptive containing 15 μg of ethinyl estradiol and 60 mg of gestodene (Adoless®) in a 24/4 regimen for three consecutive cycles. Women in Group B (n=11) used the same contraceptive regimen together with 100 mg of pycnogenol (Flebon®) continuously for 3 months. Pain scores were graded using a visual analog scale (VAS) before and during the hormone-free interval at the end of the third treatment cycle.ResultsBefore treatment, VAS pain scores for dysmenorrhea were 8 and 9 in Groups A and B, respectively. However, by the end of the third treatment cycle, pain scores had decreased significantly (P<0.05) both in groups A and B. The final pain scores were 6 in Group A and 2 in Group B, a difference that was statistically significant (P<0.0001). In Group B, 27% of the patients became pain-free, while in Group A, none of the women reported complete disappearance of this symptom. The number of bleeding days was also lower in Group B.DiscussionPycnogenol effectively decreased pain scores and the number of bleeding days when administered concomitantly with a low-dose 24/4 oral contraceptive containing gestodene.

Individualizing Selection of Hormonal Contraception

Multiple hormonal contraception methods are available to prevent unintended pregnancies. The initial selection of a hormonal method includes consideration of contraception cost, frequency of use, failure rates, timing to return to fertility after discontinuation, and medical contraindications. The Centers for Disease Control and Prevention U.S. Medical Eligibility Criteria for Contraceptive Use provides an extensive, standard reference for reviewing contraindications for contraceptive use. Following the initial selection of the hormonal contraceptive, anticipating and managing adverse effects improves adherence and consequently, prevention of unintended pregnancy. Approaches to improve tolerability include reducing the hormone free interval, adjusting the estrogen and progestin doses, and switching to a different route of administration.

Correcting oral contraceptive pharmacokinetic alterations due to obesity: a randomized controlled trial

ObjectiveTo determine if increasing the hormone dose or eliminating the hormone-free interval improves key pharmacokinetic (PK) alterations caused by obesity during oral contraceptive (OC) use. Study designObese [body mass index (BMI)≥30 kg/m2], ovulatory, otherwise healthy, women received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) dosed cyclically (21 days active pills with 7-day placebo week) for two cycles and then were randomized for two additional cycles to the following: continuous cycling (CC, a dose neutral arm using the same OC with no hormone-free interval) or increased dose (ID, a dose escalation arm using an OC containing 30 mcg EE/150 mcg LNG cyclically). During Cycles 2, 3 and 4, outpatient visits were performed to assess maximum serum concentration (Cmax), area under the curve (AUC0–∞) and time to steady state as well as pharmacodynamics. These key PK parameters were calculated and compared within groups between baseline and treatment cycles. ResultsA total of 31 women enrolled and completed the study (CC group, n=16; ID group, n=15). Demographics were similar between groups [mean BMI: CC, 38 kg/m2 (S.D. 5.1); ID, 41 kg/m2 (S.D. 7.6)]. At baseline, the key LNG PK parameters were no different between groups; average time to reach steady state was 12 days in both groups; Cmax were CC: 3.82±1.28 ng/mL and ID: 3.13±0.87 ng/mL; and AUC0–∞ were CC: 267±115 h ng/mL and ID: 199±75 h ng/mL. Following randomization, the CC group maintained steady-state serum levels whereas the ID group had a significantly higher Cmax (p<.001) but again required 12 days to achieve steady state. However, AUC was not significantly different between CC (412±255 h ng/mL) and ID (283±130 h ng/mL). Forty-five percent (14/31) of the study population had evidence of an active follicle-like structure prior to randomization and afterwards this decreased to 9% (3/31). ConclusionBoth increasing the OC dose and continuous dosing appear to counteract the impact of obesity on key OC PK parameters. ImplicationsObesity adversely affects the pharmacokinetics of very low dose OC pills. Although the impact of these changes on OC efficacy is still under debate, PK parameters can be normalized in obese users by continuous dosing or increasing to a low-dose pill.

Quality of sexual life of women using the contraceptive vaginal ring in extended cycles: Preliminary report

Objective To evaluate the quality of the sexual life of healthy women who are using a contraceptive vaginal ring (CVR) in extended cycles.Methods Fifty-two women (18 to 32 years old) seeking hormonal contraception were enrolled in this prospective study. Women were to use a CVR releasing daily 15 μg of ethinylestradiol (EE) and 120 μg of etonogestrel (ENG) for 63 days, followed by a four-day hormone-free interval, for two such extended cycles. At baseline and at the first (day 63–73) and second (day 126–134) follow-ups the Female Sexual Function Index (FSFI) and the Short Form-36 (SF-36) questionnaires were administered to investigate, respectively, sexual behaviour and the quality of life (QoL). The Female Sexual Distress Scale (FSDS) was used to verify whether sexual dysfunction caused significant personal distress to the woman.Results The FSFI and FSDS scores obtained at the first and second follow-up appointments detected an improvement with respect to the baseline score (p < 0.05). QoL measures of body pain, general health and emotional role improved at the first follow-up visit (p < 0.05); at the second one, all variables showed improvement (p < 0.05).Conclusion According to these preliminary data the CVR in extended cycles could improve the sexual function and the QoL of women.Chinese 摘 要 目的 评估在扩展周期中使用阴道避孕环健康女性的性生活质量。方法 寻求激素避孕的52名女性（18-32岁）参加了这项前瞻性研究。妇女使用阴道避孕环每天释放15μg炔雌醇和120μg依托孕烯,共63天，随后4天是无激素间歇期，持续2个这样的周期。在基础状态及第一（63-73天）和第二（126-134天）周期，用女性性功能指数（FSFI）和简化SF-36表问卷，分别对性行为和生活质量(QoL)进行调查。使用女性性障碍量表(FSDS)来证明性功能障碍是否已经引起了明显的个人困扰。结果 与基础评分相比，第一次和第二次随访时FSFI和FSDS评分明显提高（p＜0.05）。QoL评分 的身体疼痛，一般健康和情绪评分在第一次随访时明显提高；第二次随访时各项评分均明显提高。结论 根据这些初步数据，扩展周期的阴道避孕环可能会改善性功能和提高妇女的生活质量。

Return to Ovulatory Capacity With Three Combined Oral Contraceptive Regimens

INTRODUCTION: This study was designed to evaluate the effect of the combined oral contraceptive regimen LeCette (150 micrograms desogestrel and 20 micrograms ethinyl estradiol for 21 days followed by 10 micrograms of ethinyl estradiol for 7 days) and two different 28-day combined oral contraceptives on ovulation inhibition and return to ovulatory capacity. METHODS: In this phase 1, randomized, open-label comparative study, healthy, nonsmoking women aged 18–35 years with regular menstrual cycles were randomized to receive one of three combined oral contraceptives for three consecutive 28-day cycles. The three combined oral contraceptives evaluated were 21 days desogestrel and ethinyl estradiol followed by 7 days of ethinyl estradiol (desogestrel and ethinyl estradiol+ethinyl estradiol); 24 days of 3 mg drospirenone and 20 micrograms ethinyl estradiol followed by 4 placebo days (drospirenone and ethinyl estradiol and placebo); and 21 days of 100 micrograms levonorgestrel and 20 micrograms ethinyl estradiol followed by 7 placebo days (levonorgestrel and ethinyl estradiol+placebo). The proportion of women who returned to ovulatory capacity after combined oral contraceptive discontinuation was a secondary endpoint. Ovulatory capacity was defined as serum progesterone concentrations of at least 15.9 nmol/L on posttreatment cycle days 18, 19, or 20. RESULTS: A total of 206 women were randomized, 146 were evaluated for safety, and 142 were evaluated for efficacy. Greater ovarian suppression and ovulation inhibition were observed with desogestrel and ethinyl estradiol+ethinyl estradiol and drospirenone and ethinyl estradiol+placebo compared with levonorgestrel and ethinyl estradiol+placebo during the study. Return to ovulatory capacity occurred in approximately 76% desogestrel and ethinyl estradiol+ethinyl estradiol, 75% drospirenone and ethinyl estradiol+placebo, and 58% levonorgestrel and ethinyl estradiol+placebo of women. Adverse events were comparable among groups and consistent with those observed with other combined oral contraceptives. CONCLUSION: Regimens with altered or eliminated hormone-free intervals provided greater ovarian suppression with little delay in return to ovulatory capacity.

Phase 3 Study of Desogestrel and Ethinyl Estradiol Combined Oral Contraceptive for Pregnancy Prevention

INTRODUCTION: Substituting low-dose ethinyl estradiol for the typical hormone-free interval in combined oral contraceptives may enhance ovarian suppression and improve tolerability. This phase 3 study evaluated the efficacy and safety of a 28-day combined oral contraceptive regimen including 21 days of desogestrel and ethinyl estradiol followed by 7 days of ethinyl estradiol. METHODS: This was a multicenter, open-label, phase 3, single-arm study that enrolled sexually active women 18–40 years old at risk for pregnancy. Women received up to 1 year, or 13 consecutive 28-day cycles, of 150 micrograms desogestrel and 20 micrograms ethinyl estradiol for 21 days and 10 micrograms ethinyl estradiol alone for 7 days. Patients kept diaries to record compliance, bleeding or spotting, and other contraceptive use. Efficacy was measured using the Pearl Index and life table approach. Safety and tolerability were assessed through reported adverse events. RESULTS: A total of 2,858 women were enrolled and 1,680 completed the study. Forty-six pregnancies in 2,401 women aged 18–35 years occurred after combined oral contraception initiation and up to 7 days after the last desogestrel and ethinyl estradiol or ethinyl estradiol-only tablet was taken. When cycles in which another birth control method was used were excluded, the Pearl Index was 2.68 (95% confidence interval [CI] 1.96–3.57). The life table pregnancy rate was 2.47% (95% CI 1.85%–3.29%) for all users aged 18–35 years. When only cycles during which women considered compliant were included, the Pearl Index was 2.00 (95% CI 1.39–2.80). Adverse events were similar to those seen with other oral contraceptives. CONCLUSIONS: This 28-day desogestrel and ethinyl estradiol combined oral contraceptive, including 7 days of low-dose ethinyl estradiol, was efficacious and well tolerated for pregnancy prevention.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens

ObjectiveThe objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). DesignBlood samples were obtained from 62 women. ResultsWhen COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. ConclusionA more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. ImplicationsThis study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels.

Extended Cycle Combined Oral Contraceptives and Prophylactic Frovatriptan During the Hormone-Free Interval in Women with Menstrual-Related Migraines

Migraine headaches are a significant problem for American women with many of them suffering from headaches around the time of their menstrual cycle. Women taking oral contraceptives in the standard 21/7 cycle regimen often suffer from headaches around the time of the hormone free intervals (HFIs) as well. Extended oral contraceptive regimens have been shown to decrease the frequency, but not eliminate these headaches. This study is a double-blind, randomized, placebo-controlled pilot study of participants with menstrual-related migraines (MRMs) who were initiated on extended combined oral contraceptives and given frovatriptan prophylactically during HFIs. Participants having spontaneous menstrual cycles or taking daily combined oral contraceptives in a 21/7 regimen with MRMs were placed on a contraceptive containing levonorgestrel and ethinyl estradiol. Analyses compared headache scores during pre-study baseline cycles to those in a 168-day extended regimen with placebo versus frovatriptan treatments during HFIs. Daily headache scores decreased (p=0.034) from 1.29 ± 0.10 during pre-study cycles to 1.10 ± 0.14 during extended combined oral contraceptive use. Frovatriptan blocked the increase in headache score over the placebo during HFIs. However, following the withdrawal of frovatriptan, headache scores increased (p>0.01) despite resuming combined oral contraceptive use. Extended combined oral contraceptive regimen reduces MRM severity. Frovatriptan prevents headaches during HFIs, but is associated with new headache symptoms when withdrawn.

Offering extended use of the combined contraceptive pill: a survey of specialist family planning services

BackgroundThe purpose of this study was to determine attitudes to, and provision of, extended regimens for taking the combined oral contraceptive pill (COC) by specialist contraception practitioners from three contrasting specialist contraception services in London.MethodsAn online cross-sectional survey was administered to all doctors and nurses, who counsel, provide, or prescribe the oral contraceptive pill at each clinic.ResultsA total of 105 clinicians received the questionnaire and 67 (64%) responded. Only one of three clinics initiated and maintained guidelines for extended COC use. In that service, 60% of staff prescribing COC advised more than 50% of patients regarding alternative COC regimens. In the other two services, this was discussed with 20% and 6% of patients, respectively (P < 0.001). The reasons for prescribing extended use included cyclic headaches, menorrhagia, patient request, menstrual-related cramps, and endometriosis, and did not differ between the three different settings. The most common extended regimens were 63 pills or continuous use until bleeding occurs, followed by a hormone-free interval. Concerns highlighted by providers and patients were “unhealthy not to have a monthly bleed”, “future fertility”, and “breakthrough bleeding”. Such comments highlight the need for further information for providers and patients.ConclusionThere is growing evidence, backed by national guidance, about extended COC use, but routine provision of this information is patchy and varies ten-fold, even within specialist family planning services. Targeted training, use of service guidelines, and implementation research will be needed to extend patient choice of different COC regimens and change clinical practice.

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

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

Diminuer la fréquence des règles : le point sur la contraception étendue

The extended use of combined hormonal contraception contributes to a reduction of the frequency of menses by shortening the hormone free interval or the number of withdrawal weeks by year. Numerous regimen have been studied, with cycles from 49 to 365days. Most extended/continuous cycle regimens result in fewer scheduled bleeding episodes but in more unscheduled bleedings or spottings, that decrease with time. An extended contraception may be effective in reducing some menstrual symptoms such as menorrhagia or dysmenorrhea, or some menstrual related symptoms such as migraine headaches. This article reviews existing data about extended combined hormonal contraception, women's and providers’ attitude, bleeding pattern, efficacy and tolerance.

Nomegestrol acetate-17b-estradiol for oral contraception.

Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC) 2.5 mg + 17b-estradiol (E2) 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile.

Hormone withdrawal-associated symptoms: overlooked and under-explored

Women using combined oral contraceptives (COCs) report hormone withdrawal-associated symptoms (HWaS), including bloating, headaches and pelvic pain, which might be due to withdrawal of exogenous hormones and fluctuations in endogenous estrogen during the hormone-free interval (HFI). The prevalence of HWaS is not yet well studied, but these symptoms may lead to reduced user satisfaction and quality of life, and sub-optimal adherence to, and discontinuation of, COCs. HWaS are often confused with treatment-related adverse events because the timing of symptom occurrence is seldom considered. Publications on HWaS are lacking, with few guidelines and no clear consensus on the best treatment option(s). Reported treatments include continuous or extended hormonal COC regimens, which extend the time of the active hormone. Although extended-cycle regimens can cause unpredictable bleeding patterns, user satisfaction is high, with several studies reporting improvement in HWaS. Shortening the HFI is also a well-tolerated and effective method of reducing HWaS, and confers a more predictable bleeding pattern than extending the active hormone period. This may improve acceptance and long-term use of COCs. Future prospects include estradiol-based contraceptive combinations with a shortened HFI and more stable estradiol levels throughout the menstrual cycle.

Menstrual migraine, migraine and contraceptions, migraine and pregnancy and migraine triggers

More than 50% of women with migraine report an association with menstruation. Attacks are most likely to occur during the two days before menstruation and the first three days of bleeding and are typically without aura, even in women who have attacks with aura at other times of the cycle. The majority of menstrual attacks can be controlled with symptomatic treatment alone. If this is inadequate, pre-emptive treatment with perimenstrual estradiol, triptans or non-steroidal anti-inflammatory drugs (NSAIDs) may be effective. Suppression of the menstrual cycle with anovulatory contraceptive agents is an additional option for management, particularly for women who also require contraception. Using combined hormonal contraception continuously, without a break, can prevent estrogen “withdrawal” migraine during the hormone-free interval. Limited research suggests that high levels of estrogen, such as occur with use of combined hormonal contraceptives (CHCs), can trigger migraine with aura. Since aura and CHCs are independent risk factors for ischaemic stroke, the appropriateness of CHCs solely for contraception in women who have migraine with aura needs careful consideration. During pregnancy, migraine follows a benign course with improvement in migraine without aura likely by the second trimester. However, the high oestrogen state is associated with increased migraine aura in susceptible women. In these women, hypertensive disorders of pregnancy and stroke are more likely to occur although the absolute risk remains small. Women benefit from early advice on drugs that can be continued during pregnancy in order to optimize control and avoid unnecessary concern

Quality of Sexual Life of Women on Oral Contraceptive Continued-Regimen: Pilot Study

To date, women may use flexible oral contraceptive (OC) regimens. The aim of this study was to evaluate the quality of sexual life of healthy women on continued-regimen OCs. Fifty women (age range 18-38) were enrolled. The Female Sexual Function Index (FSFI) and the Short Form-36 (SF-36) questionnaires were used to investigate, respectively, sexual behavior and the quality of life (QoL) of women on OC for 72 days with a 4-day hormone-free interval, for two cycles. Both the FSFI and the SF-36 were administered before starting OC intake, at the first (72-82 days) and the second (144-154 days) follow-ups. The main outcomes are the FSFI and the SF-36 questionnaires. The FSFI score obtained at the first follow-up detected a worsening with respect to baseline score (P < 0.05). The score obtained at the second follow-up detected an improvement with respect to both the baseline and the first follow-up total scores (P < 0.05). QoL improved at the first follow-up only as regards body pain (P < 0.05), and at the second follow-up as regards: physical role, body pain, general health, vitality, and social function (P < 0.05). The use of continued-regimen OCs is able to improve the sexual behavior and the QoL of women.

Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives

BackgroundThis study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens. Study DesignThis was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12–16 and on the last day of the HFI. ResultsFrom April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12–16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01). ConclusionThis data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure.

New developments in oral contraception: clinical utility of estradiol valerate/dienogest (Natazia&reg;) for contraception and for treatment of heavy menstrual bleeding: patient considerations

New developments in oral contraception: clinical utility of estradiol valerate/dienogest (Natazia®) for contraception and for treatment of heavy menstrual bleeding: patient considerations Anita L NelsonObstetrics and Gynecology, David Geffen School of Medicine at UCLA, Harbor UCLA Medical Center, Torrance, California, USAAbstract: Natazia® is a new oral contraceptive with estradiol valerate and dienogest in a unique multiphasic formulation that includes a shortened hormone-free interval. This new formulation has been approved for both contraception and also as a treatment for heavy menstrual bleeding in women who desire to use oral contraceptives as their method of birth control. It is marketed in the US as Natazia® and elsewhere as Qlaira®. This article will review the properties of each of the major new features of this pill: estradiol used in place of ethinyl estradiol, dienogest as the progestin, and the unique dosing pattern of this product. It will also summarize the results of the pivotal clinical trials of contraceptive effectiveness, bleeding patterns, safety and tolerability. The lessons learned from the clinical trials about the effectiveness of this formulation in the treatment of excessive menstrual bleeding will be summarized. Also, results of trials comparing this new pill to other popular formulations for "menstrually-related" symptoms and for potential female sexual dysfunction related to use of oral contraceptives will be presented. This review will suggest how all this information might be used to counsel women about how to use this pill most successfully.Keywords: oral contraceptives, estradiol valerate, dienogest, heavy menstrual bleeding, menorrhagia, dynamic dosing