Clinical experience with NuvaRing® in daily practice in Switzerland: Cycle control and acceptability among women of all reproductive ages

Objectives To assess clinical experience with NuvaRing® in daily practice in Switzerland, including a large subgroup of young women (aged ≤22 years).

Methods Open, prospective, multicentre, observational clinical experience study to investigate cycle control, acceptability and usage of NuvaRing®.

Results Altogether, 2642 women participated in the programme and were included in the analysis, of which 658 were aged ≤22 years (25% of the total group). A total of 744 women (28% of the total group) discontinued NuvaRing® use; the main reason was adverse events (11% of all users). In younger women, there was a shift from moderate (?18%) and heavy (?45%) bleeding to mild bleeding (+71%) and dysmenorrhoea decreased by 60%, despite previous hormonal contraception use by 83% of women. Most women found ring insertion and removal to be straightforward (>95%), and were satisfied with its use (85%), primarily for the ring's once-a-month application (81%). Data were very similar for the total group. Cycle control and satisfaction were further improved with duration of treatment.

Conclusions In daily practice, NuvaRing® improved cycle control and was highly acceptable to women, including young women. Switchers from other hormonal methods also showed improved cycle control and high satisfaction.     

The combined contraceptive vaginal ring (NuvaRing): first experience in daily clinical practice in The Netherlands.

OBJECTIVES: The combined contraceptive vaginal ring (NuvaRing) has been shown to be safe and effective, with high levels of user compliance, acceptance and satisfaction. However, the data collected from registration studies may differ from the clinical situation. The Dutch NuvaRing Experience Project was initiated to gain insight into NuvaRing use in daily clinical practice. METHODS: A total of 1,130 women, recruited by 257 general practitioners, participated in this observational study. Data on compliance, acceptance, satisfaction, and adverse events were collected during the first 3 months of ring use via an online questionnaire. RESULTS: The results of this study were almost identical to those of the international registration studies. The majority of women complied with the prescribed regimen and were (very) satisfied with NuvaRing, primarily because of the once-a-month administration, low hormonal dose, and ease of use. Only one pregnancy was recorded throughout the study period. The bleeding pattern was better than with the pill, and there were few estrogen-related adverse events. Only a small proportion of women discontinued because of local adverse events such as discomfort during intercourse and expulsion. Following study completion, 80% of women continued with NuvaRing. CONCLUSIONS: In The Netherlands, the first clinical experiences with NuvaRing in daily practice confirm that the contraceptive ring is a reliable, safe, and convenient method of contraception.     

Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol

OBJECTIVE: The purpose of this study was to compare cycle control and tolerability of the NuvaRing (NV Organon, Oss, The Netherlands), a novel combined contraceptive vaginal ring, with a standard combined oral contraceptive pill. STUDY DESIGN: Healthy women aged 18 to 40 years who requested contraception received either NuvaRing or a combined oral contraceptive containing 30 microg ethinyl estradiol and 150 microg levonorgestrel for 6 cycles in 3 similarly designed studies. Each cycle comprised 3 weeks of ring or pill use, followed by 1 ring- or pill-free week. RESULTS: Two hundred forty-seven women began the studies, 121 women with NuvaRing and 126 women with the combined oral contraceptive. Withdrawal bleeding occurred in virtually all cycles in both groups. In the NuvaRing groups, the incidence of irregular bleeding was < or =5% in all cycles; this was lower than the combined oral contraceptive groups (5.4%-38.8%). Furthermore, the incidence of a normal intended bleeding pattern was significantly higher in the NuvaRing groups than in the combined oral contraceptive groups (P <.01). Both contraceptives were well tolerated. CONCLUSION: NuvaRing has excellent cycle control and is well tolerated.     

Cycle control, tolerability, efficacy and acceptability of the vaginal contraceptive ring, NuvaRing: results of clinical experience in Germany.

OBJECTIVES: To investigate the real-life clinical experience of NuvaRing users in Germany. METHODS: An open-label, prospective, uncontrolled, non-randomized, multicentre postmarketing surveillance study was conducted by 1204 gynaecologists amongst 5823 women requesting contraception. The women underwent routine examinations and contraceptive counselling, and were assessed after three and six cycles of NuvaRing use. RESULTS: Good cycle control was observed and there was a reduction in cycle irregularity and inter-menstrual bleeding, bleeding duration and intensity, and dysmenorrhoea. NuvaRing was well tolerated, and had no significant effect on body weight or blood pressure. Nine women became pregnant unintentionally (two had conceived before they started to use NuvaRing, three due to non-compliance, one because of repeated ring expulsion/loss and three during treatment in spite of having applied this latter as instructed). Most women expressed their satisfaction with NuvaRing; 82% were 'very satisfied/ satisfied', 72% planned to continue using it and 82% would recommend it to others. More than 90% of women found NuvaRing 'without problems/easy' to insert and to remove, and more than 80% of the women and their partners were not disturbed by its presence during intercourse. CONCLUSION: NuvaRing is a highly effective and acceptable method of once-monthly contraception that is safe and well tolerated.     

The combined contraceptive vaginal device (NuvaRing): a comprehensive review.

OBJECTIVES: The aim of this study is to review the development of NuvaRing over the past decade to illustrate its use-effectiveness and acceptance as an alternative contraceptive option for women. METHODS: The data were extracted from the literature using computerised MEDLINE system. NuvaRing is a new combined hormonal contraceptive vaginal ring made of ethylene-vinyl-acetate copolymer, releasing 120 microg etonorgestrel and 15 microg ethinyloestradiol per day. This ring is inserted on any day from day 1 to day 5 of a menstrual cycle for 21 days, thereafter removed for 7 days ring-free period and discarded. RESULTS: Complete inhibition of ovulation is observed during treatment with this device. Clinical exposure to NuvaRing for 1786 women-years has resulted in 21 pregnancies, giving a Pearl Index of 1.18. Withdrawal bleeding (4.7-5.3 days) is regular (97-99% of cycles) with rare incidence of irregular bleeding (2.6-6.4%). The cycle control is good with the use of this combined contraceptive vaginal ring. NuvaRing is well tolerated and accepted by women as compared to oral pill. CONCLUSIONS: NuvaRing is an effective vaginal contraceptive option for women. However, further study is needed for monitoring its long-term effectiveness and impact on patient's quality of life since the NuvaRing is marketed in many countries.     

The combined contraceptive vaginal ring (NuvaRing®): First experience in daily clinical practice in The Netherlands

Objectives The combined contraceptive vaginal ring (NuvaRing^®) has been shown to be safe and effective, with high levels of user compliance, acceptance and satisfaction. However, the data collected from registration studies may differ from the clinical situation. The Dutch NuvaRing Experience Project was initiated to gain insight into NuvaRing use in daily clinical practice.

Methods A total of 1130 women, recruited by 257 general practitioners, participated in this observational study. Data on compliance, acceptance, satisfaction, and adverse events were collected during the first 3 months of ring use via an online questionnaire.

Results The results of this study were almost identical to those of the international registration studies. The majority of women complied with the prescribed regimen and were (very) satisfied with NuvaRing, primarily because of the once-a-month administration, low hormonal dose, and ease of use. Only one pregnancy was recorded throughout the study period. The bleeding pattern was better than with the pill, and there were few estrogen-related adverse events. Only a small proportion of women discontinued because of local adverse events such as discomfort during intercourse and expulsion. Following study completion, 80% of women continued with NuvaRing.

Conclusions In The Netherlands, the first clinical experiences with NuvaRing in daily practice confirm that the contraceptive ring is a reliable, safe, and convenient method of contraception.     

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial

Objectives: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15?μg ethinylestradiol [EE] and 120?μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30?μg EE and 3?mg drospirenone in healthy Chinese women aged 18–40 years.

Methods: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study.

Results: Participants were randomised either to the NuvaRing (n?=?732) or to the COC (n?=?214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result.

Conclusions: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.     

Use of the NuvaRing hormone-releasing system in late reproductive-age women with type 1 diabetes mellitus.

AIM: To evaluate the effect of the vaginally inserted hormone-releasing system NuvaRing on carbohydrate and lipid metabolism and the hemostasis system, over 6 months of use, in late reproductive-age women with type 1 diabetes mellitus (DM). METHODS: The open randomized study included a total of 25 women with type 1 DM using NuvaRing. Average daily insulin requirements, levels of glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3 and 6 months of contraception. The control group was composed of 20 age-matched women with type 1 DM using no methods of contraception, as well as 20 apparently healthy women using the NuvaRing device. RESULTS: Use of the NuvaRing contraceptive system in type 1 DM women in the late reproductive period was shown to exert no clinically significant effect on carbohydrate and lipid metabolism on the background of persistent and satisfactory compensation of carbohydrate metabolism (HbA1c < or = 7.5%), with a neutral impact on the hemostasis system. CONCLUSION: The NuvaRing hormone-releasing system proved to be a reliable and safe means of contraception for late reproductive-age women with type 1 DM.     

Combined contraceptive ring versus combined oral contraceptive (30-μg ethinylestradiol and 3-mg drospirenone)

Objectives

To compare the adverse effects, cycle control, and metabolic effects of NuvaRing and a combined oral contraceptive (COC).

Methods

Women seeking contraception received NuvaRing (n = 300) or a COC (n = 300) for 12 cycles in a randomized, open-label trial.

Results

The total number of women with adverse effects did not differ significantly between the 2 groups. Leucorrhea, vaginitis, decreased libido, and ring-related problems were more common with NuvaRing, whereas weight increase, acne, and emotional lability were more common with the COC. Breakthrough bleeding occurred in 11.3% of women receiving NuvaRing and in 14.7% of women receiving the COC; 2.1% and 2.9% of women, respectively, had no withdrawal bleeding. Differences in blood pressure, blood sugar levels, lipid profile, liver enzyme activity, and anticoagulant activity were not statistically significant, with the exception of low-density lipoprotein levels measured at 6 and 12 months, which were significantly lower in the NuvaRing group than in the COC group.

Conclusions

NuvaRing is a good alternative to a COC. It is associated with a slightly reduced incidence of breakthrough bleeding and there were no clinically relevant adverse effects or changes in blood pressure, blood sugar levels, lipid profile, or anticoagulant activity when compared with the COC.     

The relationship of bleeding patterns to daily reproductive hormones in women approaching menopause

OBJECTIVE: To discover early hormonal predictors of menopause and the stages of the menopausal transition and to understand the hormonal basis behind the bleeding abnormalities common in the menopausal transition. METHODS: A cohort of 804 women aged 42-52 collected first void urine samples daily for one complete menstrual cycle or 50 days (whichever came first) once a year for 3 years. Urine was assayed for excreted levels of follicle-stimulating hormone, luteinizing hormone, estrogen metabolites, and progesterone metabolites, which were normalized for creatinine concentration. Anovulation was defined by an algorithm based on progesterone secretion. Menstrual bleeding parameters were derived from daily calendars. Correlations among bleeding characteristics, hormone concentrations, and other potential clinical predictors were analyzed using multivariable logistic regression models. RESULTS: An ethnically diverse population of women (mean age of 47) with a majority in the early perimenopause was studied. Approximately 20% of all cycles were anovulatory. Short cycle intervals (fewer than 21 days) were common early in the menopause transition and were associated with anovulation (44%). Long cycle intervals (more than 36 days) also were associated with anovulatory cycles (65%). Both short (1-3 days) and long (more than 8 days) duration of menstrual bleeding were associated with anovulation (18% and 23%, respectively). Women with anovulatory cycles were less likely to report heavy menstrual bleeding as compared with those with ovulatory cycles. Heavy bleeding was not associated with steroid hormone concentrations but was associated with obesity and with the self-reported presence of leiomyomata. CONCLUSIONS: Among women in the early menopause transition, abnormalities in timing of menstrual bleeding (cycle intervals or bleeding duration) have a hormonal basis and are frequently associated with anovulation. In contrast, abnormally heavy periods do not appear to have a steroid hormonal basis and are less likely after anovulatory cycles. Heavy periods are associated with obesity and leiomyomata. LEVEL OF EVIDENCE: II.     

Health-related quality of life in young women starting hormonal contraception: a pilot study

Objectives: Our purpose was to study whether there is a difference in self-rated health-related quality of life (HRQOL) and changes in HRQOL perception after 3 months of hormonal contraceptive use in adolescents. Seasonal variations in symptoms of depression were also studied.

Methods: A test group (T1) (n?=?193) and a selected control group (n?=?238) of women aged 14–20 years who were visiting a young person’s clinic completed the 36-item short-form health survey (SF-36) and answered additional questions on menstrual history and pattern, need for menstrual pain relief medication, and other regular medication. The test group was reassessed after 3 months of hormonal contraception (T2). Seasonal variations in reported SF-36 scores were studied for the whole group.

Results: The selected control group and test group at T1 were similar with regard to age at menarche and menstrual pattern. The duration of bleeding and use of painkillers were significantly reduced and the impact on everyday life was significantly improved after 3 months of hormonal contraception (p?=?.000, two-tailed). No changes in HRQOL or symptoms of possible depression were found after 3 months of hormonal contraception. The highest prevalence odds ratio for possible depression (SF-36 mental health scale score ≤48), adjusted for group, season and age, for spring vs winter, was 2.15 (95% confidence interval 0.95, 4.85).

Conclusions: After 3 months of hormonal contraception both the number of days of menstrual bleeding and the use of medication to relieve menstrual pain were reduced, but there were no significant changes in self-rated HRQOL perception. Seasonal effects on HRQOL were reported.     

Oral micronized progesterone combined with vaginal progesterone gel for luteal support

The aim of the present study was to compare the efficacy and satisfaction rate of combined therapy of oral micronized progesterone capsules and vaginal progesterone gel versus monotherapy with vaginal progesterone gel in luteal support. A case–control study was performed on a total number of 370 women aged?<45 years undergoing IVF-ET treatment. The patients received either combination of Crinone 8% vaginal gel, 90?mg daily dose and Utrogestan oral capsules 3×100?mg, or Crinone 8% vaginal gel, 90?mg daily. Progesterone supplementation begun on the day of oocyte retrieval and continued until pregnancy was tested and in the case of pregnancy until week 8. The comparable rates of ongoing pregnancies were noted with use of combined-progesterone therapy (39.5%) and progesterone-monotherapy (33.5%). Abortion rate (6.4% vs. 15.6%) was significantly lower with the use of combined therapy. Tolerability and satisfaction of both supplements was almost equal but bleeding occurred more frequently in the progesterone-monotherapy group. In conclusion, the efficacy, satisfaction and tolerability of combined and vaginal progesterone supplements were comparable, but bleeding in early pregnancy and abortion rate presented more frequently with the use of vaginal progesterone.     

Cyclic menstruation-like bleeding during denied pregnancy. Is there a particular hormonal cause?

OBJECTIVE: To investigate whether particular hormonal patterns could explain the persistence of cyclic menstruation-like bleeding during denied pregnancies. METHODS: Hormone measurements were performed immediately after delivery in a total of 28 subjects with denied pregnancies. The results were studied in three patient subgroups: subjects with any cyclic bleeding during pregnancy (n = 22), subjects with cyclic bleeding during pregnancy until the delivery date (n = 7) and subjects with amenorrhea (n = 6). These data were compared with those of a control group (n = 126). In some of the women who reported cyclic bleeding, hormone assessments were also done once the lactation period ended. RESULTS: For estradiol, free estriol and progesterone, no more than two values in each group were outside the 95% confidence interval of the control group. Several results for prolactin were remarkably lower. The findings for human chorionic gonadotropin, free testosterone, dehydroepiandrosterone sulfate, alpha-fetoprotein and thyroid-stimulating hormone were almost all within the 95% confidence interval. In seven subjects, abnormal results were obtained for the gondaotropin-releasing hormone/thyrotropin-releasing hormone test and the metoclopramid test after delivery and lactation. All of these subjects showed signs of corpus luteum insufficiency. In five subjects, evidence of hyperprolactinemia was found. CONCLUSION: Results revealed that hormonal patterns assessed immediately after delivery do not provide any causal explanation for the cyclic menstruation-like bleeding that occurs during denied pregnancies. Hormone assessments performed after the lactation period, i.e. during a normal menstrual cycle, showed a number of abnormalities. However, a causal relationship could not be drawn.     

A meta-analysis on the correlation between ovarian activity and the incidence of intermenstrual bleeding during low-dose oral contraceptive use.

We aimed to evaluate potential correlation between ovarian activity during use of combined oral contraceptives and the incidence of intermenstrual bleeding. Data from seven prospective clinical studies with five different combined low-dose oral contraceptives were retrospectively analyzed to determine ovarian activity measured by the Hoogland Score (follicle diameter and endogenous hormone levels) and cycle control. A total of 227 young fertile women were evaluated over three treatment cycles each. Women with intermenstrual bleeding had statistically significantly higher estradiol levels than those without intermenstrual bleeding. Also, women with intermenstrual bleeding had significantly larger follicle-like structures than those without intermenstrual bleeding. For example, in the second treatment cycle the difference of the mean follicle diameters between women without intermenstrual bleeding (12.5 mm) and women with spotting (16.9 mm) or breakthrough bleeding (16.1 mm) was statistically significant (p = 0.0179). Less than 17% of women with Hoogland Score 1, 2 or 3 (low ovarian activity) reported intermenstrual bleeding. On the other hand, 35.2% of women with Hoogland Score 4 (active follicle-like structures) reported intermenstrual bleeding. The association between bleeding and Hoogland Score was statistically significant (p < 0.0011). The findings of this retrospective analysis provide evidence that high ovarian suppression is positively correlated with improved cycle control in terms of less frequent intermenstrual bleeding - slight and heavy.     

Use of 52-mg Levonorgestrel-Releasing Intrauterine System in Adolescents and Young Adult Women: 3-Year Follow-Up

Study ObjectiveTo evaluate continuance rates, bleeding patterns, and patient satisfaction with 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) use in adolescents and young adult women during the first 3 years of useDesignWe conducted an observational prospective study.SettingFamily Planning Service of a tertiary hospital in BrazilParticipantsOne hundred adolescents and young women aged 16-24 years.InterventionInsertion of 52-mg LNG-IUS for the main purpose of contraception. Follow-up visits were conducted at 12, 24, and 36 months after insertion.Main Outcome MeasuresContinuance rates, reasons for discontinuation of the method, and women's satisfaction and bleeding patternsResultsAmong those who were not lost to follow-up, LNG-IUS continuance rates were 89.1% (82/92), 82.9% (72/87), and 75.3% (64/85) in the first, second, and third years of use, respectively. The main reason for discontinuation was acne, followed by expulsion of/malpositioned LNG-IUS. Other reasons for discontinuation were irregular uterine bleeding, dysmenorrhea, and abdominal pain. The amenorrhea rates were 50%, 54.1%, and 39% at 12, 24, and 36 months, respectively. Spotting rates increased during the first 3 years of use (20.8%, 16.7%, and 26.6%, respectively). Adolescents and young women using the LNG-IUS showed high rates of satisfaction, with 93.9%, 100%, and 96.8% of women being very satisfied/satisfied in the first 3 years of use. Only 2 participants who continued using the LNG-IUS reported being very dissatisfied/dissatisfied in the third year of follow-up.ConclusionThe LNG-IUS showed high rates of continuation and satisfaction in the first 3 years of use in Brazilian adolescents and young adults. Most women reported a favorable bleeding pattern.     

A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function.

OBJECTIVES: To compare carbohydrate metabolism, adrenal and thyroid function during use of a combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) with those of a combined oral contraceptive. METHODS: Healthy women aged 18-40 years used either the vaginal ring, delivering 15 microg ethinylestradiol and 120 microg of etonogestrel per day, or a combined oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, for six cycles. Each cycle comprised 3 weeks of use of the ring or the pill followed by 1 ring- or pill-free week. The following parameters were measured at baseline and at the end of cycles 3 and 6: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin); adrenal function (total cortisol, cortisol binding globulin, dehydroepiandrosterone sulfate); thyroid function (thyroid stimulating hormone, free thyroxine). RESULTS: Small and similar increases in insulin were seen in both groups. Concentrations of cortisol binding globulin and total cortisol rose significantly less during ring use than during combined oral contraceptive use (cycle 3, p= 0.0002; cycle 6, p < 0.0001). Levels of dehydroepiandrosterone sulfate did not change in either group. Thyroid stimulating hormone levels increased significantly more in the ring group at cycle 3 (p = 0.0016) but free thyroxine levels were unchanged in both groups. CONCLUSIONS: Both the vaginal ring and the oral contraceptive have no clinically relevant effects on carbohydrate metabolism, adrenal or thyroid function.     

Do young women have specific problems in contraceptive use and counselling?

OBJECTIVES: To find out if young women have specific problems with the use of contraception or contraceptive services. STUDY DESIGN: A national postal survey was conducted, RR 74%. Women aged 18-34 years (with experience of contraceptive use) were included in this report (n=1239). RESULTS: Weekly need for contraception was highest in the age group 18-24 years (61%), oral contraception being the most widely used method regardless of parity. Condoms were used by 35-37% in all age groups, either alone or combined with oral contraceptives (17% of young nulliparas). Women aged 18-24 years had mainly used public or subsidized services (79%). Of quality characteristics, only satisfaction with the kindness of the service provider varied significantly by age. The cost of contraception was highest in the youngest age group. CONCLUSIONS: The study did not point at any serious problems in family planning among young women, but it did produce several clues for the development of family planning services in general.     

人工流产术后即刻放置依托孕烯植入剂避孕的可行性研究

目的:探讨人工流产术后是否可即刻放置依托孕烯植入剂进行避孕。方法:要求避孕的66例因非意愿妊娠行人工流产术后妇女即刻放置依托孕烯植入剂为研究组,另同期征集84例健康妇女于月经期放置该植入剂作为对照组,术后1、6、12个月随访,随访阴道出血情况,植入剂取出原因,并在放置12个月时进行满意度调查。结果:在放置12个月期间所有对象均未怀孕。研究组闭经/出血稀发发生率为53.0%,出血频发/出血延长发生率为15.1%,对照组闭经/出血稀发发生率为58.4%,出血频发/出血延长发生率为27.3%;满12个月时,研究组取出20例,续用率为69.7%,满意度为69.6%;对照组取出22例,续用率为73.8%,满意度为72.6%。结论:人工流产术后即刻放置依托孕烯植入剂与月经期放置效果相同,人工流产术后妇女即刻放置依托孕烯植入剂进行避孕也是一个较合适的放置时机。     

Menstrual bleeding patterns in pre- and perimenopausal women: a population-based prospective diary study

BACKGROUND: To investigate natural menstrual bleeding patterns in pre- and perimenopausal women, a prospective observational population study was carried out. METHODS: A total of 1616 (80.8%) of a population-based sample of 2000 Danish women aged 45-54 years answered an initial questionnaire. Of 1059 women with natural gynecological functions, 951 (89.8%) completed 1 year of daily recording of bleeding. Of these women, 592 were pre- or perimenopausal and were included in this study. MAIN OUTCOME MEASURES: Length and heaviness of bleeding episodes, including frequency of spotting, flooding and prolonged bleeding, according to regularity of cycles. RESULTS: The proportion of women with irregular cycles increased from 58.3% at age 45-46 years to 100% at age 53-54 years (P < 0.001). Irregularity of cycles was accompanied by increased variation in both length and subjective assessment of heaviness of bleeding episodes in the individual woman and between women (P < 0.001). Episodes of spotting (P < 0.001) and prolonged bleeding (10 days or more) (P < 0.001) were more common in women with irregular cycles. Subjective assessment of heaviness of bleeding episodes, however, was higher in women with regular cycles (P < 0.001). One or more episodes of flooding were recorded by 24.0% of all women irrespective of regularity of cycles (P = 0.40) but more frequently in younger women (P < 0.001). CONCLUSIONS: Irregularity of cycle lengths at the end of the fertile period is common, and is accompanied by an increased inter- and intraindividual variation in the length and heaviness of bleeding episodes, including increased frequency of prolonged bleeding and spotting.     

Uterine bleeding pattern during low dosage Noretisterone acetate and 17-b-Estradiol treatment in postmenopausal patients

BACKGROUND: Recent years have been characterized by progressive optimization of postmenopausal hormonal replacement therapy. More physiological therapeutic protocols have been, in fact, proposed to control the possible symptomatology and to prevent the associated risks, with estro-progestinic compounds characterized by lower effective dosages and suitable for the single patient need. However this therapy is not widely accepted by the women from our country for the fears and the inconvenience raised around such side effects as abnormal uterine bleeding and spotting. Aim: to obtain a good compliance and clinical benefits a continuous administration protocol of the hormonal replacement therapy, alternatively to the sequential one has been proposed. METHODS: Our research group has been observing a sample of 42 patients for 12 months, taking oral 17-b-estradiol 1 mg/noretisterone 0.5 mg in continuous administration. All of them were aged from 42 to 63 years and had been in symptomatic menopause for at least 3 months. The characteristics, the onset and the trend of vaginal bleeding were registered in appropriate monthly diaries. Endometrial thickness was evaluated by transvaginal sonography before starting the administration, not exceeding 4 mm in all the women considered. RESULTS: The incidence of bleeding (calculated as a percent of women who experienced a vaginal bleeding for al least a day during a menstrual cycle) was from 26% to 32% in the 1st trimester, reducing during the following months. At 6 months of therapy only 5% of women reported evident vaginal bleeding; at 12 months 90% of women complained with absence of bleeding or spotting. At 12 months no women showed an endometrial thickness over 6 mm. CONCLUSIONS: This observational study suggests that the majority of treated patients proved to be positively responsive to the treatment and that the 17-b-estradiol 1 mg/noretisterone 0.5 mg association reduces the incidence of bleeding and spotting with a sufficient endometrial protection from hyperplasia.