A collaborative study of the progesterone intrauterine device (progestasert)

A randomised double blind study of a plain T-shaped IUD and an active T-shaped IUD releasing 65 μg/day of progesterone, has been completed in four centres.

A study of 1320 progesterone-releasing IUDs in parous women for 9660 women months of use significant to 18 months, gave a pregnancy rate of 1.9 ± 0.4, expulsion of 4.7 ± 0.6 and removals for pain and bleeding of 6.0 ± 0.7.

A detailed analysis of the menstrual bleeding patterns in these patients gave details of the number and length of bleeding and spotting episodes, count of bleeding days, and count of spotting episodes and days for four one-hundred-day reference periods. While the plain IUD contributed a significant number of intermenstrual spotting and bleeding days, the progesterone-releasing IUD contributed more spotting days.     

The association between vaginal bleeding patterns and reasons for discontinuation of contraceptive use

This paper describes the relationship between menstrual bleeding patterns recorded and reasons for discontinuing method use given by women using one of four types of hormonal contraception: combined oral pills, progestogen-only oral pills, a vaginal ring or depot-medroxyprogesterone acetate (DMPA). The women were recruited to five clinical trials, each of which lasted at least 48 weeks. The subject's reason for discontinuation was recorded if she stopped contraceptive use before the scheduled time. Overall, the reason expressed for discontinuing method use was a close reflection of the subject's experience. Among women using either type of oral contraceptive or a vaginal ring, subjects who discontinued for a non-menstrual reason or were lost to follow-up had bleeding patterns which did not differ markedly from those of women who continued method use. Only in the DMPA group was there any evidence that women who complained of non-menstrual side effects or were lost to follow-up might have ceased method use because they were unwilling or unable to tolerate their bleeding patterns. Subjects who discontinued because of amenorrhea had few bleeding/spotting days and at least one prolonged bleeding-free interval; women who complained of longer bleeding had long episodes and short intervals. Women who reported heavier bleeding had patterns which were similar to, but less extreme, than those of subjects who reported longer bleeding. The complaint of irregular bleeding, however, did not concur with the bleeding patterns recorded, regardless of contraceptive method. The predominant menstrual disturbance in this group of women was frequency of bleeding. They had no special difficulty in predicting either the time of onset or the length of their bleeding episodes. There were marked differences between individuals in terms of their acceptance of bleeding disturbances. Nevertheless, the results of this study confirm the importance of counselling. Women using DMPA tolerated far greater menstrual disruption than subjects using any other method. Subjects using an oral contraceptive were unlikely to have been warned of potential bleeding problems; when they encountered any, they tended to cease method use. In contrast, subjects using DMPA would have been advised to expect irregular patterns and possibly amenorrhea; prepared for such disturbances, their perseverance was remarkable.     

Vaginal bleeding patterns among women using one natural and eight hormonal methods of contraception

Menstrual diary records were obtained from a total of 5257 women using nine different methods of contraception, one natural and eight hormonal. This paper presents a comparative analysis of their vaginal bleeding patterns. The analytic procedures follow the recommendations of a recent WHO workshop on bleeding pattern analysis, which involve dividing each subject's diary into successive 90-day reference periods, calculating ten indices for each period, and classifying women according to whether they have "clinically important" bleeding disturbances. In general, the findings of this analysis confirm those of previous studies. Women using the natural method, who were deliberately selected for the regularity of their menstrual cycles, averaged three bleeding/spotting episodes of length 5 days in each 90-day period, with very little variability within or between women. Subjects given a combined oral contraceptive had more regular patterns than any other treated group, with short (4-day) episodes and 23-24 day bleeding-free intervals. Progestogen-only pill users had more frequent, longer episodes and shorter, less predictable intervals than combined pill users. Contrary to widely-held beliefs, the progestogen-only pills produced fewer spotting days than the combined pills, and almost no spotting episodes at all. Nearly half of vaginal ring users experienced some menstrual disturbance in each period; their most common problems were irregular, infrequent or prolonged bleeding. Women using the long-acting injectable, depot medroxyprogesterone acetate, had totally unpredictable patterns, with infrequent but prolonged bleeding/spotting episodes. The incidence of amenorrhea rose from just under 10% in their first injection interval to over 40% in their fourth. The methods of analysis recommended by WHO in 1985 still require substantial refinement. Nevertheless, they are more sensitive than those used previously for WHO trials and produce an easily understood, clinically meaningful characterization of bleeding patterns.     

Bleeding patterns of adolescents using a combination contraceptive injection for 1 year

PURPOSE: This prospective observational study evaluated the bleeding patterns of adolescents receiving a monthly injectable contraceptive containing norethisterone enanthate 50 mg plus estradiol valerate 5 mg. MATERIALS AND METHODS: The study enrolled 73 volunteers aged between 14 and 19 years; of these patients, 38 (52%) recorded their menstrual cycles during 1 year. RESULTS: After 1 year of using the contraceptive, most of the 38 women (71.1%) had adequate menstrual patterns (two to four bleeding episodes; none lasting 10 days or longer; with a range of bleeding-free intervals not exceeding 17 days), 23.7% reported prolonged bleeding episodes, 2.6% had irregular bleeding and 2.6% had amenorrhea. Only 1 of the 38 teenagers is known to have discontinued the method due to bleeding. Among these 38 adolescents, dissatisfaction with bleeding patterns was not a frequent reason given for discontinuation of the monthly injectable contraceptive.     

Bleeding and spotting with the levonorgestrel 13.5 mg intrauterine system: the impact of insertion timing

ObjectiveTo assess the impact of early versus late menstrual cycle insertion on bleeding/spotting in the 90 days following levonorgestrel (LNG) 13.5 mg intrauterine system (IUS) insertion.Study designIn this observational study, participants received a LNG 13.5 mg IUS and provided 90 days of bleeding/spotting data by answering the following daily text: “Have you had no flow (0), spotting (1), or bleeding (2) today?” We dichotomized insertion timing as early (days 1–7 from last menstrual period) and late (remainder of menstrual cycle) and compared bleeding/spotting between the two groups in the 90- and 30-day reference periods. We used multivariate regression methods to study associations between cycle day at insertion, parity, historical bleeding, recent hormonal contraceptive use and bleeding/spotting.ResultsIn the 90-day dichotomous analysis (n=125), we found no differences in the number of days of bleeding/spotting, bleeding or spotting between the early and late insertion groups. In the 30-day dichotomous analysis (n=131), early insertion was associated with fewer days of bleeding than late insertion (5±3 vs. 7±4 days, p<.01). Recent hormonal contraceptive users experienced fewer days of bleeding than new users (5±4 vs. 7±3 days, p<.01). In the 90- and 30-day regression models, earlier insertion was associated with fewer days of bleeding (p=.02, p=.02). Recent contraceptive use was associated with fewer days of bleeding/spotting (90-day, p=.03) and fewer days of bleeding (30-day, p<.01). Nulliparity was associated with spotting (30-day, p=.04).ConclusionsEarly cycle insertion does not impact 90-day bleeding/spotting. Early cycle insertion and recent hormonal contraceptive use decrease 30-day bleeding.ImplicationsThe LNG 13.5 mg IUS may be inserted throughout the menstrual cycle with small differences in bleeding patterns in the 30 but not the 90 days following insertion. Shared decision making should determine timing of insertion.     

Bleeding patterns of women using extended regimens of the contraceptive vaginal ring

INTRODUCTION: This prospective observational study evaluated the bleeding patterns of women using a vaginal ring releasing 120 microg of etonogestrel and 15 microg of ethinyl estradiol daily, over a continuous period of 84 days followed by 7 ring-free days. METHODS: The study enrolled 75 volunteers aged 18 to 37 years. Sixty-two (82.8%) recorded their menstrual cycles during 1 year. RESULTS: At the end of the study, 85.5% had adequate menstrual patterns (two to four bleeding episodes, none lasting 10 days or more, with a range of bleeding-free intervals not exceeding 17 days), 9.7% had infrequent bleeding, 1.6% reported prolonged bleeding episodes, 1.6% had frequent bleeding and 1.6% had irregular bleeding. CONCLUSION: Only 5 of the initial 75 patients discontinued the method due to bleeding. Among these 75 women, dissatisfaction with bleeding patterns was not a frequent reason given for discontinuation of the contraceptive vaginal ring.     

Determinants of menstrual bleeding patterns among women using natural and hormonal methods of contraception. II. The influence of individual characteristics

Menstrual diary records were obtained from women using either a natural method of contraception, a combined or progestogen-only oral contraceptive, a vaginal ring, or a long-acting injectable (DMPA). Within each method group, multiple regression analysis was used to examine the relationships between the subjects' bleeding patterns and their age, age at menarche, ponderal index, obstetric and contraceptive history and ethnic origin. The influence of ethnic origin was described in the preceding paper. Among combined pill users, increasing age was associated with more frequent spotting episodes. In both the untreated and combined pill groups, women with a higher ponderal index had less variable bleeding-free intervals; in the vaginal ring and DMPA groups, the more obese women had shorter bleeding/spotting episodes and longer bleeding-free intervals. Among combined oral contraceptive users, the most influential variable was the time since the end of the woman's last pregnancy: subjects who had been more recently pregnant had longer, less predictable episodes and shorter intervals. Previous oral contraceptive use was associated with more predictable bleeding patterns among women currently using either type of oral pill. In the vaginal ring and DMPA groups, subjects whose last pregnancy had ended in abortion had more bleeding/spotting days and episodes than those who had had a live birth. As reported previously, bleeding patterns were more closely related to the woman's geographical region of residence than to any other factor. The associations found with other individual characteristics were often inconsistent or difficult to interpret. A number of variables which could potentially influence menstrual bleeding patterns, such as nutritional status, were not measured and therefore could not be included in the analysis. However, contraceptive method and ethnic origin may be predominant influences, overriding any other factor.     

Using a low-dose contraceptive in women 35 years of age and over: 20 microg estradiol/100 microg levonorgestrel

The efficacy, safety, and cycle control of a low-dose oral contraceptive (OC) containing 20 μg ethinyl estradiol (EE) and 100 μg levonorgestrel (LNG) has been demonstrated in a large trial with 1708 women (≥15 years old with regular menstrual cycles). The objective of this study was to analyze the same parameters in 218 of the 1708 women who were 35 years of age and older. Women were administered the 28-day, combination OC (20 μg EE/100 μg LNG; 21 days active medication/7 days placebo) for up to 3 years. During 3859 cycles evaluated for efficacy, one pregnancy occurred (Pearl index 0.34). The most common adverse events cited as reasons for discontinuation were hypertension (3% of subjects), headache (2%), and metrorrhagia (2%). One subject withdrew as a result of a serious adverse event. Breakthrough bleeding, spotting, and bleeding and spotting occurred in 2.9%, 11.0%, and 6.8%, respectively, of the 3739 cycles evaluated for cycle control. This low-dose, monophasic regimen of 20 μg EE/100 μg LNG is an effective, safe, and tolerable contraceptive and provides good cycle control for women 35 years of age and older.     

Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons

Background

Many women want a lengthy duration of contraception but are wary of the menstrual changes from depot medroxyprogesterone acetate (DMPA). A subdermal levonorgestrel (LNG) implant may be a reasonable alternative. However, information on menstrual changes from these methods has not been summarized and compared in an easy-to-understand form.

Study Design

We systematically reviewed the published literature on these contraceptives to find research that used menstrual diaries and standard World Health Organization definitions. We attempted to find information on amenorrhea, number of bleeding or spotting episodes, number of bleeding or spotting days and normal patterns, as reported in four consecutive 90-day reference periods.

Results

We found 16 published articles meeting our criteria and involving diaries of up to 1600 DMPA users and 2300 LNG implant users. We were able to compare the two methods on only three outcomes. For DMPA use, the weighted prevalence of amenorrhea at successive 90-day periods was 12%, 25%, 37% and 46%. The comparable estimates for the LNG implant were 11%, 13%, 9% and 13%. Levonorgestrel implant users experienced a higher average number of bleeding or spotting days compared to DMPA users, but this average was similar to what is expected naturally. At 12 months, normal menstrual patterns were experienced by 23% of LNG implant users compared to 11% of DMPA users.

Conclusions

Like most hormonal contraception, LNG implants usually produce menstrual changes; however, the changes do not appear to deviate from normal patterns as much as the changes from DMPA. Understanding these differences and other method attributes might help women make an informed choice about which contraceptive to use.     

Effect of intermittent treatment with mifepristone on bleeding patterns in Norplant implant users

A double-blind, placebo-controlled, randomized trial, was carried out in 120 Norplant users to evaluate the effect of mifepristone, 100 mg/day administered for 2 consecutive days every 30 days, on the vaginal bleeding pattern. Treatment was given from months 2-7 of implant use. Volunteers recorded bleeding and spotting days, during treatment and for the ensuing 6-month period. During treatment, women on mifepristone recorded the same frequency of bleeding/spotting episodes but significantly less prolonged bleeding episodes than placebo controls (mean +/- SD: 11 +/- 3 vs. 22 +/- 23 days) and their total number of bleeding days was 35% lower than in the placebo group. After the end of mifepristone use, bleeding patterns were similar in both groups. One pregnancy occurred in the mifepristone-treated group, in month 6 of treatment, the outcome was a healthy male baby. We conclude that intermittent administration of mifepristone can offer a clinically significant improvement of the vaginal bleeding pattern in Norplant users.     

Immediate postabortal insertion of a levonorgestrel-releasing IUD

Experimental IUDs releasing only 10 μg levonorgestrel per day and established copper-releasing IUDs (Nova-T) were inserted in 60 women in connection with legal first-trimester abortion. Bleeding and spotting and other events were recorded during the first year. Restoration of the menstrual cycle was studied. Blood samples were collected twice a week over a three-month period from five women receiving a levonorgestrel-releasing IUD to determine plasma levels of estradiol, progesterone, levonorgestrel, LH and FSH. FSH showed an increase approximately ten days (range 4–19) after abortion. LH/hCG concentrations reached a plateau approximately 24 days (range 9–42) after abortion. Initially, levonorgestrel concentrations were two-fold compared with concentrations of 90 pg/ml after four weeks. After four weeks the plasma levonorgestrel concentrations were stable. All five women had an ovulatory menstrual cycle. The first periods occurred 35 days after operation in the levonorgestrel-IUD group and 30 days after operation in the Nova-T group. The median duration of bleeding and spotting after the insertion was 12 days (range 3–26) in the Nova-T group and 12.5 days (range 3–93) in the levonorgestrel-IUD group. The difference was not statistically significant. From the second month on, menses-like bleeding was more common in the copper-releasing IUD group than in the levonorgestrel-IUD group. The difference was statistically significant (p < 0.001). After one year 75 percent of the patients continued with their IUDs in both groups. One pregnancy occurred in the experimental levonorgestrel-IUD group. One total expulsion was noticed in both groups, and one partial expulsion in the levonorgestrel-IUD group. Two levonorgestrel-IUDs and four Nova-Ts were removed because of bleeding and/or pain. One infection was noticed in the whole group six days after the operation. In the levonorgestrel-IUD group 74 percent of the women had a regular cycle after one year, while all Nova-T patients had a regular cycle. Twelve percent (7 women) were lost to follow-up at one year. The results of this study suggest that a levonorgestrel-releasing IUD can be inserted after legal first-trimester abortion and the results are comparable with those of previous studies that have been made using copper-releasing IUDs.     

Menstrual bleeding patterns among regularly menstruating women

Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005-2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.     

Determinants of menstrual bleeding patterns among women using natural and hormonal methods of contraception. I. Regional variations

Records of the occurrence of vaginal bleeding were obtained from women using either a natural method of contraception or one of four types of hormonal contraceptive. The relationships between their bleeding patterns and a number of demographic variables were examined, with the aim of identifying subgroups of women who, if they used a particular hormonal method of contraception, would be likely to suffer more or less disruption to their bleeding pattern than the 'norm'. Within contraceptive method, bleeding patterns were more closely related to the women's geographical region of residence than to any other factor. Some of the differences between regions were consistent across contraceptive methods. European women tended to have more bleeding/spotting days than women in other regions; Latin American women had relatively short episodes and long bleeding-free intervals, whether they were using the ovulation method, combined pills or a vaginal ring. Other differences were method-specific. Women using combined pills in India or Pakistan had fewer spotting episodes than women using the same method elsewhere; those using progestogen-only pills had more. Regional variations in bleeding patterns were particularly marked among women using DMPA, and increased over time: by their fourth injection interval, 25% of European women had amenorrhea, as compared with 72% of subjects in North Africa. These findings need to be confirmed by carefully controlled studies of menstrual bleeding patterns and their acceptability in various ethnic groups. The results would be valuable in counselling new contraceptive acceptors, and could eventually guide the choice of methods for introduction into national family planning programmes.     

国产Ⅰ型、Ⅱ型埋植剂与Norplant使用第1年阴道出血模式的观察与比较

为了解两种国产埋植剂对阴道出血模式的影响,并与Norplant进行比较,对自1993年11月1日～1994年5月31日随机接受的857例埋植剂使用者记录的月经卡(其中国产Ⅰ型288份,国产Ⅱ型292份,Norplant277份),采用WHO推荐的参考时段法进行统计分析。结果:各项统计指标三组间差异均无显著意义;总出血天数和滴血天数各参考时段均有减少,自第3参考时段起差异有显著意义;各种出血类型的发生率三组间无差异,有基本正常出血类型的人数自第2参考时段明显增加,为30％～35％;出血不规则的发生率自第2参考时段明显减少,为34％～41％,但仍为各种异常出血的首位;再次使用埋植剂者的总出血天数和出血天数均少于首次使用者,差异有显著意义。初步认为两种国产埋植剂在使用后第1年中对阴道出血模式的影响与Norplant相似,阴道总出血天数随滴血天数的减少而缩短;与使用初期相比,使用三种埋植剂后三个月,有基本正常出血类型的人数明显增加,出血不规则的发生率明显减少,出血不规则是埋植剂使用后月经紊乱的主要表现;再次使用者的出血情况好于初次使用者。     

A multicenter study of levonorgestrel—Estradiol contraceptive vaginal rings III — Menstrual patterns: An international comparative trial

Menstrual events among users of contraceptive vaginal rings (CVRs), releasing levonorgestrel and estradiol, were studied in comparison with a combined oral contraceptive, Nordette,¹ in multicentered trials. CVRs were made with outside diameters of 50 and 58 mm and released about 250 μg and 290 μg of levonorgestrel and 150 μg and 180 μg of estradiol per day, respectively. The CVRs were used continuously for 3 weeks and then removed for 1 week. Both the CVRs and Nordette were perceived to reduce menstrual flow and days of menstrual bleeding. Twenty to 25% of CVR users perceived increased inter menstrual bleeding or spotting. Diaries indicate, however, that on average, CVR users experienced about 1 day per month of bleeding or spotting with the ring in place. CVRs and Nordette produced approximately the same total number of bleeding and spotting days during 6 cycles of use, 27–29, but the small (50-mm OD) ring was associated with somewhat more spotting. This ring was also associated with somewhat more prolonged bleeding and spotting runs and with more prolonged nonbleeding intervals than reported by users of the larger (58-mm OD) ring or of Nordette. Differences among regimens, however, tended to be small even when statistically significant. Evidence from menstrual diaries indicates that these CVRs, and in particular the 58-mm ring, provide control over the menstrual cycle comparable to that of Nordette.     

Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel

OBJECTIVES: The safety and efficacy of a single-rod implantable contraceptive containing etonogestrel (Implanontrade mark) were investigated in a multicenter clinical trial. STUDY DESIGN: Sexually active American women (N=330) with apparently normal menstrual cycles used the implant for up to 2 years. All subjects recorded bleeding and/or spotting daily in a diary. Safety was assessed through adverse experiences (AEs), laboratory tests and physical and gynecologic examinations. RESULTS: Total exposure was 474 woman-years (6186 cycles), and 68% of subjects had at least 1 year of exposure. No pregnancies occurred. The most common bleeding pattern observed throughout the study was infrequent bleeding, defined as less than three episodes of bleeding in a reference period (excluding amenorrhea). The least common pattern was frequent bleeding, defined as more than five episodes of bleeding in a reference period. Infrequent, prolonged and frequent bleeding patterns were most common early in the study and declined thereafter. During the 3-month Reference Periods 2-8 (Months 4-24), the incidence of amenorrhea ranged from 14% to 20%. Forty-three subjects (13%) withdrew from the study because of bleeding pattern changes and 76 subjects (23%) discontinued because of other AEs. Other common AEs leading to discontinuation, besides bleeding irregularities, were emotional lability (6.1%), weight increase (3.3%), depression (2.4%) and acne (1.5%). Use of Implanon (etonogestrel subdermal implant, referred to herein as ENG implant) for up to 2 years had no clinically significant effects on laboratory parameters, physical and pelvic examinations, vital signs or body mass index. The average length of time required for ENG implant insertion and that for removal were 0.5 and 3.5 min, respectively, and all the procedures were uncomplicated. The return to normal menstrual cycles and fertility was rapid after removal. CONCLUSIONS: Implanon is a safe, highly effective and rapidly reversible new method of contraception.     

黄体期使用米非司酮配伍米索前列醇避孕对月经影响的临床研究

目的:探讨妇女在无保护性生活超过120h,或多次无保护性生活后在黄体期使用米非司酮配伍米索前列醇避孕对月经的影响。方法:观察对象在黄体期一次性服用米非司酮100mg并在36～48h后服用米索前列醇400μg,服药后随访2个月经周期。结果:在成功避孕的289例(98.6%)中,服药前月经周期29.36±2.14d,服药当月月经周期26.15±3.68d,差异有统计学意义(t=15.498,P<0.05);服药前经期5.42±1.02d,服药后当月经期5.61±1.09d,差异有统计学意义(t=-4.143,P(0.05);服药后当月经量与自身既往经量比较,无变化215例(74.4%),减少59例(20.4%),增多15例(5.2%)。服药后次月月经周期为29.65±2.82d,与服药前相比差异无统计学意义(t=-1.922,P>0.05);经期5.46±1.03d,与服药前比较差异无统计学意义(t=-1.609,P>0.05);经量无变化273例(94.5%),减少10例(3.5%),增多6例(2.1%)。服药距预计月经时间越长月经提前的时间就越长(F=3.445,P<0.05)。结论:妇女黄体期使用米非司酮配伍米索前列醇避孕有效率高,可使服药当月月经周期缩短、经期延长,且服药距预计月经时间越长对月经影响越大,但对以后月经无影响。     

米非司酮不同服用方法对皮下埋植术后子宫出血影响的观察

目的:探讨米非司酮不同服用方法对皮下埋植避孕术后子宫异常出血的影响。方法:120例行皮下埋植避孕术妇女随机分为3组,每组40例。对照组不服用任何药物;一日组在埋植日和每月月经来潮当日服米非司酮50mg,共服6次;两日组在埋植日和每月月经来潮当日、次日各服米非司酮25mg,共服6次。结果:服用米非司酮期间出血天数和滴血天数较对照组减少(P<0.01),经期延长和长期不规则出血百分率低于对照组(P<0.05),但一日组和两日组间差异无显著意义(P>0.05)。停药后组出血天数较对照组明显减少(P<0.05)、滴血天数差异无显著性意义(P>0.05),一日组和两日组间差异无显著性意义(P>0.05)。结论:皮下埋植术后单次服用米非司酮可以改善术后子宫异常出血。     

A prospective cohort study of menstrual characteristics and time to pregnancy

The authors examined the association between menstrual characteristics and time to pregnancy among 2,653 Danish women enrolled in a prospective cohort study (2007-2009). Menstrual characteristics were reported at baseline. Outcome data were updated bimonthly until pregnancy, fertility treatment, loss to follow-up, or end of observation (12 cycles). Adjusted fecundability ratios and 95% confidence intervals were estimated by using discrete-time Cox regression models. Relative to average cycle lengths (27-29 days), fecundability ratios for cycle lengths <25, 25-26, 30-31, 32-33, and ≥34 days were 0.64 (95% confidence interval (CI): 0.49, 0.84), 0.94 (95% CI: 0.77, 1.13), 1.10 (95% CI: 0.97, 1.25), 1.35 (95% CI: 1.06, 1.73), and 1.17 (95% CI: 0.91, 1.49), respectively. Compared with cycles that regularized within 2 years after menarche, fecundability ratios for cycles that regularized 2-3 and ≥4 years after menarche were 0.90 (95% CI: 0.80, 1.02) and 0.89 (95% CI: 0.77, 1.03), respectively. Fecundability ratios were 0.87 (95% CI: 0.72, 1.05) comparing <3 with 3-4 days of menstrual bleeding and 0.70 (95% CI: 0.43, 1.13) comparing very heavy with moderate flow. In the present study, shorter cycle length was associated with delayed time to pregnancy. Age at menarche, time to menstrual regularization, and duration or intensity of menstrual flow were not appreciably associated with fecundability.     

Menstrual cycle characteristics: associations with fertility and spontaneous abortion

BACKGROUND: Epidemiologists often use menstrual cycle patterns as indicators of endocrine function in environmental and occupational studies, yet few studies have considered whether menstrual cycle characteristics are associated with fertility or pregnancy outcome. METHODS: We prospectively studied 470 women to determine whether cycle length or bleed length were associated with fertility or spontaneous abortion. Women completed daily diaries with information on menstrual bleeding, intercourse, birth control use, and covariates. For each menstrual cycle, women collected at least 2 urine samples, which were assayed for human chorionic gonadotropin to define early pregnancies. Women were followed for 1 year or until the end of a clinical pregnancy. RESULTS: Cycles with lengths of 30 to 31 days preceded cycles with the highest fecundity. Shorter cycles were less likely to be followed by conception (fecundity ratio [FR] = 0.6; 95% confidence interval [CI] = 0.4-1.0). Compared with 30- to 31-day cycles, conceptions after shorter and longer cycles were more likely to be spontaneously aborted (for shorter cycles, odds ratio [OR] = 3.0 [95% CI = 0.9-9.6] and for longer cycles, OR = 3.0 [0.9-10.6]). Cycles with 5 days of menstrual bleeding had the highest fecundity. Cycles with up to 4 days of bleeding had lower fecundity (for bleed lengths of 4 days, FR = 0.5 [0.3-0.8] and for bleed lengths less than 4 days, FR = 0.6 [0.3-0.9]). Spontaneous abortion was less likely after bleeds greater than 5 days (OR = 0.4 [0.1-1.1]) when compared with 5-day bleeds. CONCLUSIONS: Menstrual cycle characteristics appear to be associated with fertility and spontaneous abortion.