Symptoms of uterine myomas: data of an epidemiological study in Germany.

PURPOSE: Currently, no reliable data are available concerning the type and frequency of symptoms in premenopausal women with uterine myomas. METHODS: 2296 women were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. From this population, 1314 premenopausal women between the ages of 30 and 55 years were evaluated to determine the type and frequency of myoma-related symptoms and their relationship to anamnestic factors, and the number, size, and location of the myomas. Standardised questionnaires were used to record the symptoms. RESULTS: Prevalence: In almost every second premenopausal woman (n = 639; 48.6%), uterine myomas were diagnosed. The frequency of myomas increased continuously with age and was highest in women between 46 and 50 years (65.2%). Age itself was found to be the main risk factor for the presence of myomas (p < 0.001). SYMPTOMS: 54.3% (n = 347) of the women suffered from myoma-related symptoms. The four main symptoms were identified as: Heavy menstrual bleeding (40.7%), dysmenorrhoea (28.2%), lower abdominal pain (14.9%), and intermenstrual bleeding (14.1%). In the majority of cases, the symptoms occurred simultaneously. Determinants for symptoms: Symptoms did not follow a clear age-related trend, whilst the number and size of the myomas did determine the presence of symptoms. The main influencing factor for the presence of intermenstrual bleeding was the location of the myomas. CONCLUSIONS: The high prevalence of uterine myomas highlights the importance of the diagnosis uterine myomas in standard gynaecological practice: The presence of only one myoma caused symptoms in 46.5% and small myomas of up to 2 cm in diameter resulted in symptoms in 39.5%.

Prevalence of uterine myomas in women in Germany: data of an epidemiological study.

PURPOSE: Currently, no reliable data are available concerning the prevalence of uterine myomas in Germany. In this prospective study, we examined the prevalence of myomas in women older than 30 years by means of vaginal ultrasound. METHODS: 2296 women, who consented to the procedure, were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. PREVALENCE: myomas were detected in 41.6 % of all women. Age dependence: With increasing age, the prevalence of uterine myomas rose from 21.3 % (30-35 years) to 62.8 % (46-50 years). Later, the number of myomas decreased again from 56.1 % (51-55 years) to 29.4 % in women older than 55 years. Menarche/BMI: no correlation could be found between the age at first menstrual period or the body mass index and the occurrence of myomas. Parity: since the group of nulliparous women and the group of women with more than four deliveries stand out by increased occurrence of myomas, a non-linear correlation seems to exist, necessitating more in-depth discussion with regard to age dependency. CONCLUSIONS: The results of this study suggest that more than 40 % of women over 30 years of age suffered from myomas and more than 50 % of all women in Germany may develop uterine myomas at some time in their life.

Long-term medical management of uterine fibroids with ulipristal acetate.

OBJECTIVE: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN: Double-blind, randomized administration of four 12-week courses of ulipristal acetate. SETTING: Gynecology centers. PATIENT(S): Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. INTERVENTION(S): Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. MAIN OUTCOME MEASURE(S): Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. RESULT(S): Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. CONCLUSION(S): The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. CLINICAL TRIAL REGISTRATION NUMBER: NCT01629563.

Drospirenone-only oral contraceptive: results from a multicenter noncomparative trial of efficacy, safety and tolerability.

OBJECTIVES: This study was performed to assess the contraceptive efficacy of the drospirenone (DRSP)-only pill and to provide information regarding its safety and cycle-control profile. STUDY DESIGN: This prospective, multicenter, noncomparative study was conducted at 41 European sites in healthy women at risk of pregnancy, aged 18 to 45 years. The study medication was DRSP 4.0mg daily for 24 days followed by a placebo for 4 days (DRSP 4 mg 24/4, Exeltis, Spain) for thirteen 28-day treatment cycles. The primary efficacy endpoint was the overall Pearl Index (PI). Bleeding patterns, changes in vital signs and changes in laboratory values were also analyzed. RESULTS: A total of 713 participants with 7638 DRSP treatment cycles were analyzed. The overall PI was 0.51 (95% confidence interval, 0.1053-1.4922). The proportion of participants with any bleeding decreased from 72.7% in Cycle 1 to 40% in Cycle 6 and 32.1% in Cycle 13. Unscheduled bleeding decreased from 49.1% in Cycle 1 to 27.8% in Cycle 6 and to 22.8% in Cycle 13. Prolonged bleeding was reported by 6.5% during Cycles 2 to 4 decreasing to 4.2% during Cycles 11 to 13. There were no reports of deep vein thrombosis, pulmonary embolism or hyperkalemia. No relevant changes were observed for laboratory parameters, body weight, body mass index, blood pressure or heart rate. Study drug acceptability was considered as "excellent/good" by over 82% of subjects. CONCLUSION: This new DRSP-only oral contraceptive provides clinical contraceptive efficacy similar to that of the currently marketed Combination estrogen plus progestin Oral Contraceptive, with a good safety profile, and favorable cycle control. IMPLICATIONS: A novel 4-mg DRSP-only pill taken daily for 24 days followed by a placebo for 4 days demonstrated contraceptive efficacy similar to that of currently marketed Combination estrogen plus progestin Oral Contraceptive, with a good safety profile, and favorable cycle control.

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

OBJECTIVE: To 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). METHODS: This 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. RESULTS: In 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. CONCLUSION: Both 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.

Contraceptive counselling and factors affecting women's contraceptive choices: results of the CHOICE study in Austria.

Empirical evidence of the impact of contraceptive counselling and factors affecting women's contraceptive choices are limited. CHOICE (Contraceptive Health Research Of Informed Choice Experience) was a large-scale study in 11 European countries. Women in Austria aged 15-40 years considering a short-acting, reversible form of combined hormonal contraceptive were eligible to participate. The choices included the combined daily pill, weekly transdermal patch, and monthly vaginal ring. This study assessed and compared 2478 women's original preferences with their post-counselling choices and evaluated their perceptions and criteria for their choice. Women who were 'undecided' decreased from 18.1% pre-counselling to 3.2% post-counselling; significantly more women post-counselling chose the monthly ring (8.7% to 23.8%; difference 15.1%, 95% CI 13.3-16.8%; P<0.0001) or the weekly patch (6.2% to 7.8%; difference 1.7%, 95% CI 0.5-2.9%; P=0.0014). Women's primary reasons for choosing a method included 'easy to use' (daily pill, weekly patch and monthly ring) and 'still effective if I experience vomiting, diarrhoea' (weekly patch and monthly ring). Structured and balanced counselling led to changes in the method chosen.

Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque Implanon: an open-label, noncontrolled, multicenter trial.

BACKGROUND: The etonogestrel (ENG) implant Implanon is a progestin-only contraceptive that provides effective contraception for up to 3 years. A new radiopaque ENG implant has been developed to extend the diagnostic modalities of Implanon and a next-generation applicator (NGA) was designed to facilitate correct subdermal insertion of Implanon. STUDY DESIGN: In this open-label study, 23 investigators, experienced and inexperienced with Implanon, performed 301 insertions of the new radiopaque implant using the NGA. Primary outcome measurements were obtained from clinician satisfaction questionnaires completed after the 4th, 8th and 12th insertions. Additionally, insertion characteristics and X-ray visibility were assessed. RESULTS: Almost all investigators were satisfied with the NGA from the first insertion onward, and all were satisfied or very satisfied after 12 insertions. The most frequently reported advantages included ease of use, one-handed action and fast insertion time; 2% of insertions were considered difficult in skin puncturing and/or sliding the needle subdermally. Three incorrect insertions occurred due to noncompliance with instructions. All assessed implants were visible on plain X-ray imaging. CONCLUSIONS: The NGA was well accepted by investigators with or without prior experience with Implanon. The results stressed the importance of correctly following implant insertion instructions.

Advantages and challenges of oestrogen-free hormonal contraception.

BACKGROUND: Not all women tolerate hormonal contraceptives containing oestrogens. METHODS: The authors selected and evaluated relevant publications on the advantages and challenges of oestrogen-containing and oestrogen-free oral contraceptives obtained from the MEDLINE and Google databases from January 2000 to January 2010. In addition, the reference lists from the obtained publications as well as the authors' clinical experience served as additional sources of information. Emphasis was placed on the common adverse effects and risks associated with oestrogen replacement as well as on the noncontraceptive benefits of combined oral contraceptive pills and progestogen-only pills in the management of menstrual cycle-dependent problems. FINDINGS: Progestogen-only pills have the potential to abolish many of the common adverse effects associated with oestrogen plus progestogen oral contraceptives and can be used to treat various menstrual cycle-dependent problems. However, only a limited number of clinical comparative studies are available. Progestogen-only pills are associated with a more irregular bleeding pattern than contraceptive pills containing oestrogens, especially during the first few months of therapy. As this is not permanent, adequate counselling is essential in order to prevent unnecessary discontinuation of treatment. CONCLUSIONS: Progestogen-only pills offer an effective, convenient, and readily reversible method of contraception that is suitable for women with contraindications for oestrogens.

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

BACKGROUND: This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. STUDY DESIGN: This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. RESULTS: Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. CONCLUSIONS: A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.

The effects of an oestrogen-free, desogestrel-containing oral contraceptive in women with cyclical symptoms: results from two studies on oestrogen-related symptoms and dysmenorrhoea.

OBJECTIVES: To evaluate the effects of an oestrogen-free oral contraceptive (Cerazette; 75 mcg/day desogestrel) in women with oestrogen-related symptoms during previous combined oral contraceptive (COC) use (ERS study) and in women with dysmenorrhoea (DYS study). METHODS: Two similarly designed prospective, non-comparative multicentre observational studies were carried out in Germany. Altogether, 403 women with oestrogen-related symptoms during previous COC use and 406 women with dysmenorrhoea took Cerazette continuously. Symptom-related assessments were made at baseline and after 3-4 months, along with bleeding pattern and treatment satisfaction. RESULTS: In the ERS study, the four oestrogen-related symptoms studied resolved or improved in over 70% of women. Nausea improved/resolved most (92% of women), followed by breast tenderness (90%), oestrogen-related headache (84%) and oedema (74%). In the DYS study, dysmenorrhoea resolved or considerably improved in 93% of the study population. Correspondingly, use of analgesics dropped from 70% of women at baseline to 8% at study end. Adverse events were reported by 7-8% of both study populations and were mainly bleeding irregularities. Most women in both studies were satisfied with treatment (approximately 90%) and wished to continue treatment after study completion (approximately 85%). CONCLUSIONS: Cerazette in this study set-up improved oestrogen-related symptoms and dysmenorrhoea in women affected and treatment was well accepted.

Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.

PURPOSE: This randomized multicenter, open-label, trial compared efficacy, acceptability, tolerability and compliance of NuvaRing with a combined oral contraceptive (COC), containing 30 microg of ethinyl estradiol (EE) and 3 mg of drospirenone. METHOD: In this 13-cycle study, 983 women were randomized and treated (intent-to-treat population) with NuvaRing or COC. RESULTS: One in-treatment pregnancy occurred with NuvaRing (Pearl Index=0.25) (95% confidence interval [CI]: 0.006, 1.363) and four with the COC (Pearl Index=0.99) (95% CI: 0.269, 2.530). For both groups, compliance (89.2% NuvaRing, 85.5% COC) and satisfaction (84% NuvaRing; 87% COC) were high; the vast majority of women found NuvaRing easy to insert (96%) and remove (97%). Tolerability was similar; the most frequent adverse events with NuvaRing were related to ring use, whereas estrogen-related events were more common with the COC. CONCLUSION: NuvaRing has comparable efficacy and tolerability to a COC containing 30 microg of EE and 3 mg drospirenone. User acceptability of both methods was high.