In two international, randomized, double-blind, 24-week, phase 3 trials involving women with uterine fibroid–associated heavy menstrual bleeding, therapy with relugolix (an oral ...gonadotropin-releasing hormone receptor antagonist), combined with estradiol and norethindrone acetate, led to a significant reduction in menstrual bleeding while preserving bone mineral density.
In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with ...uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.
Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.
Overall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.
Improvements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.
ClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.
Myovant Sciences GmbH.
This is a summary of research studies (known as clinical trials) called LIBERTY 1 and LIBERTY 2. The LIBERTY 1 and LIBERTY 2 studies looked at how well a medication called relugolix combination ...therapy worked to reduce heavy bleeding at the time of menstruation compared with placebo. The studies also looked at what side effects were reported in women with uterine fibroids and heavy menstrual bleeding.
Researchers looked at 388 adult women in the LIBERTY 1 study and 382 adult women in the LIBERTY 2 study. All women had heavy menstrual bleeding with uterine fibroids before the start of the LIBERTY 1 and LIBERTY 2 studies. The women were given one of three treatments during the studies: relugolix combination therapy or placebo for 24 weeks, or delayed relugolix combination therapy (relugolix alone for the first 12 weeks, then relugolix combination therapy for the last 12 weeks of the studies). More women taking relugolix combination therapy in the LIBERTY 1 study (73%) and LIBERTY 2 study (71%) had menstrual blood loss of less than one-third of a cup (80 mL) and had reduction of at least 50% less blood loss during their last menstrual period after 24 weeks of taking the medicine compared with placebo (LIBERTY 1: 19% and LIBERTY 2: 15%). The women taking relugolix combination therapy also had less pain than those taking placebo. Side effects were similar across treatment groups. Headaches and hot flushes were the most common side effects.
More women with uterine fibroids taking relugolix combination therapy for 24 weeks were likely to have fewer uterine fibroid symptoms than women receiving placebo.
NCT03049735 (LIBERTY 1); NCT03103087 (LIBERTY 2).
To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLAⓇ) containing levonorgestrel (LNG) and ethinyl estradiol (EE).
This ...single-arm, open-label, multicenter, 1-year (13 cycle), phase 3 study enrolled sexually active women ≥18 years old at risk for pregnancy irrespective of body mass index (BMI). Women used patches in 28-day cycles (3 consecutive administrations of 7-day patches followed by 7 days off-treatment/patch-free week). We assessed contraceptive efficacy by the Pearl Index (PI) in women 18 to 35 years, excluding cycles without intercourse or when other contraceptive methods were used.
The study enrolled 2032 demographically diverse women in the US, of which 35.3% had a BMI ≥30 kg/m2. In the primary efficacy analysis, the PI (95% confidence interval) was 5.8 (4.5–7.2) pregnancies per 100 woman-years. PIs trended higher as BMI increased; the PI was 4.3 (2.9–5.8) in women with BMI <30 kg/m2 and 8.6 (5.8–11.5) in women with BMI ≥30 kg/m2. Hormone-related treatment-emergent adverse events included nausea (4.1%) and headache (3.6%); 11% of women discontinued due to adverse events. Four women (all with BMIs ≥30 kg/m2) reported thromboembolic events considered related to treatment.
The low-dose LNG/EE TDS was effective in preventing pregnancy in a population of women representative of US demographics. Efficacy was reduced in women with BMI ≥30 kg/m2. The TDS safety and tolerability profile was consistent with other similar dose combined hormonal contraceptives. Results of this phase 3 study supported the US Food and Drug Administration approval of TWIRLAⓇ for prevention of pregnancy in women with BMI <30 kg/m2.
TDS (120 µg/day levonorgestrel and 30 µg/day ethinyl estradiol) is an effective, low-dose transdermal contraceptive patch with favorable tolerability profile approved for prevention of pregnancy in women with BMI <30 kg/m2. TDS has reduced effectiveness in women with BMI ≥30 kg/m2.
Higher rates of unwanted pregnancies and lower rates of contraceptive use have been reported among Hispanic women than among non-Hispanic whites. Despite these differences, it is unclear how these ...groups differ with respect to various psychosocial factors that are associated with contraceptive decision making, including contraceptive knowledge, attitudes, self-efficacy and social support.
A total of 443 sexually active, nonpregnant, low-income women (137 non-Hispanic whites, 74 US-born Hispanics and 231 non-US-born Hispanics) were surveyed at two publicly funded clinics.
The greatest number of barriers to the effective use of contraception was seen among non-US-born Hispanic women. Fewer differences emerged between US-born Hispanics and whites, although differences continued to exist between the two groups in certain key areas. As compared to non-Hispanic whites, US-born Hispanic women had lower levels of social support for and self-efficacy in contraceptive use, desired larger families, had more religious objections to using birth control and were more those likely to believe that birth control use is the responsibility of women. As compared to whites, both US and non-US-born Hispanic women had significantly lower rates of ever-use of contraceptives that are highly effective in preventing pregnancy or in preventing disease transmission, and higher rates of unintended pregnancies. All associations were independent of known confounders.
Despite improvements in contraceptive knowledge and attitude, birth control and disease-preventive practices did not improve significantly among Hispanics who were born in the United States. Hispanic women are at higher risk for unintended pregnancy than are non-Hispanic whites, irrespective of their US nativity.
Context: Hormonal contraceptive users may be at increased risk for HIV and other STDs. An understanding of their decisions and abilities to use condoms is needed to focus intervention programs aimed ...at improving their protective behaviors. Methods: Between 1999 and 2001, 426 new users of depot medroxyprogesterone acetate (DMPA) and oral contraceptives were recruited from public clinics providing family planning services to low-income women and surveyed when they began their method and again three months later. Bivariate analyses examined the consistency of condom use across subgroups, and multivariate analyses assessed associations between consistent use and various characteristics. Results: Among women who had used condoms consistently before starting on DMPA or the pill, 54% discontinued consistent use after taking these contraceptives. Overall, 20% of women consistently used condoms with their hormonal method, and such use did not vary significantly by contraceptive type. Seventy-five percent of women in nonmonogamous relationships were inconsistent users, though nearly a third had been consistent users prior to beginning a hormonal method. Factors associated with an elevated likelihood of consistent use were the male partner's positive opinion of condoms (odds ratio, 3.3) and the woman's strong belief that condom use is important for vaginal intercourse (3.5) and even if the couple is using another form of birth control (4.1). Conclusions: Many women at highest risk for disease have a decreased likelihood of using condoms, and disease prevention programs should be customized to target these women. Educational efforts focusing on women's attitudes and negotiation skills may be the best means of increasing dual method use.
Abstract Objective To examine physicians’ views and practices concerning estrogen + progestogen therapy (EPT). Design Questionnaires were mailed to a random sample of physicians in the United States ...(US) in 2003. A total of 1614 (53.8%) surveys were returned (633 obstetricians and gynecologists (Ob/Gyns), 571 family practitioners, and 410 internists). Results Only a minority of the physicians (16%) would offer EPT to menopausal women in the absence of menopausal symptoms (26% Ob/Gyn, 11% family practitioners, 6% internists, p < 0.0001). However, many physicians (62%) believed that EPT could be offered “short term” to menopausal women with menopausal symptoms assuming no contraindications (82% Ob/Gyn, 54% family practitioners, 42% internists; p < 0.0001). Irrespective of specialty, the strongest contraindications to EPT use reported by these physicians were personal history of breast cancer (93%), thrombosis (92%), cerebrovascular disease (84%), ischemic heart disease (74%), uterine cancer (73%), as well as women's subjective “concern” about breast cancer (57%). Procedures reported as always required by physicians for continuing women on EPT were breast examination (97%), mammogram (96%), blood pressure measurement (94%), and pelvic examination (91%). Conclusions Internists and family practitioners address more contraindications to EPT use than Ob–Gyns. Although many physicians appear to be accepting of short-term use of EPT for menopausal indications in the absence of contraindications, the majority would not prescribe it for prophylactic purposes.
To report the prevalence of endometriosis and its associated risk factors among multiparous women, and to determine the relationship between the location and depth of this disease and certain medical ...and behavioral characteristics.
Over a 6-year period, 3384 multiparous women underwent laparoscopy for tubal sterilization. Endometriosis was detected in 126 patients (3.7%), who were consequently evaluated for severity of the disease. To conduct a case-control study, 504 patients with no evidence of endometriosis were randomly selected from a group of women who underwent sterilization. Information obtained through physical examination and a self-administered questionnaire was studied by multivariate logistic regression analysis.
Most endometriosis lesions were minimal. Factors associated with an increased risk for endometriosis included: advanced age (odds ratio OR 2.0, 95% confidence interval CI 1.1–3.7), Asian race (OR 8.6, 95% CI 1.4–20.1), long cycle length (OR 1.8, 95% CI 1.1–2.7), one live birth (OR 2.2, 95% CI 1.1–4.3), long duration of intrauterine device use (OR 3.0, 95% CI 1.1–8.1), and long duration of uninterrupted menstrual cycles (OR 2.9, 95% CI 1.3–6.4). Present oral contraceptive use was protective for disease (OR 0.5, 95% CI 0.2–0.9). The role of these factors varied among different disease locations (ovary, uterus and tubes, posterior broad ligaments and cul-de-sac), and depth (superficial or deep).
The prevalence of endometriosis is relatively low among multiparous women, and certain menstrual and reproductive characteristics are associated with its development. Furthermore, the relationship between various factors and endometriosis appears to be site and depth specific. Our findings suggest that asymptomatic endometriosis may be clinically important.
The purpose of this study was to examine the independent role of paternal influences on the onset of prenatal care among Hispanic women.
A total of 300 pregnant Hispanic women seeking prenatal care ...on or before their 35th week of gestation were surveyed about their and their partner's pregnancy intention. Women in this study were recruited from clinics providing services to low income and medically indigent women.
Father's pregnancy intention had a protective effect on the timely onset of prenatal care. Pregnancies that were unintended by the mother but were intended by the father had a lower likelihood of delayed care, as compared to those unintended by both (Odds Ratio OR = .54, 95% confidence interval CI = .28, .99). This trend was stronger among married than non-married couples.
Comprehensive efforts are needed to involve male partners in family planning as well as in programs aimed at expanding adequate pre- and postnatal behaviors within Hispanics.
Recent studies suggest that the progesterone receptor isoforms (PR-A and PR-B) activate genes differentially and that PR-A may act as a repressor of PR-B function. Hence, the absolute and relative ...expression of the two isoforms will determine the response to progesterone. We have measured their relative expression in the uterus of cycling women who underwent endometrial biopsy. PR isoforms were identified on blots of SDS-PAGE gels by reaction with the AB-52 antibody after immunoprecipitation from endometrial extract. Both isoforms were highest in the peri-ovulatory phase, but levels of PR-A were always higher than those of PR-B. The ratio of PR-A to PR-B changed during the menstrual cycle. Between days 2 and 8, PR-B is almost undetectable and the A:B ratio is >10:1. From days 9 to 13, the ratio is about 5:1, and it is about 2:1 between days 14 and 16. Thereafter, PR-B dwindles rapidly and is virtually undetectable at the end of the cycle. In various hypoestrogenic environments, PR-B expression was reduced. However, exogenous estrogens in the follicular phase in the form of oral contraceptives, enhanced PR-B expression. These data support the possibility that progesterone acts through cycle-specific PR isoforms.
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