Evaluation of menstrual bleeding patterns: a new proposal for a universal guideline based on the analysis of more than 4500 bleeding diaries

Objective To develop a universal guideline allowing the comparison of interventions like oral contraceptives and hormone replacement therapy with an impact on menstrual bleeding pattern.

Methods Literature analysis and cluster analysis of 4612 bleeding diaries.

Results We summarized key definitions needed for the evaluation of menstrual bleeding patterns from the literature. We developed a methodology to systematically evaluate menstrual bleeding patterns that distinguishes between cyclical and continuous hormonal regimens.

Conclusion This universal guideline can be applied to all prospective clinical studies that affect menstrual bleeding patterns. It allows regulatory agencies and prescribing physicians to make meaningful comparisons of different products.     

The length of menstrual bleeding and the risk of urogenital infections in the context of the activity of hemoglobin-derived microbicidal peptides

OBJECTIVE: Well-known natural unspecific antimicrobial factors acting in the vagina are additionally reinforced during menstrual bleeding by hemocidins--a recently discovered novel class of microbicidal peptides generated proteolytically from hemoglobin. The aim of the presented research was to investigate the relation between the average length of menstrual bleeding and the frequency of urogenital infections. We expected that the shorter menstrual bleeding might increase the risk of urogenital infections because is synonymous with the shorter period of exposition on bactericidal action of hemocidins. STUDY DESIGN: The study contains statistical analysis of an average declared length of menstrual bleeding in the group of 267 young, sexually active women with the symptoms of urogenital infections. The control group consisted of 300 young healthy women. RESULTS: The length of menstrual bleeding in the group of patients with urogenital infections (average 4.35 days) was statistically significantly shorter than in the control group (average 4.95 days). The average length of the menstrual cycle was equal and counted ca. 28 days in both groups. CONCLUSION: The length of menstrual bleeding seems to be a significant factor in the vaginal ecology maintenance.     

Follicular phase hormone levels and menstrual bleeding status in the approach to menopause

OBJECTIVE: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels. DESIGN: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years. SETTING: Women in Philadelphia County, PA, identified by random-digit telephone dialing. PARTICIPANT(S): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436). DATA COLLECTION: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period. MAIN OUTCOME MEASURE(S): Serum levels of follicular E(2), FSH, inhibin B, and LH. RESULT(S): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30. CONCLUSION(S): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.     

Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial

OBJECTIVE: To assess bleeding patterns with continuous use of the transvaginal contraceptive ring. METHODS: We did a prospective analysis of daily menstrual flow during a 21/7 cycle followed by 6 months of continuous use and institution of a randomized protocol to manage breakthrough bleeding/spotting. Seventy-four women completed the baseline 21/7 phase and were randomized equally into two groups during the continuous phase. Group 1 was instructed to replace the ring monthly on the same calendar day with no ring-free days. Group 2 was instructed to use the same process, but if breakthrough bleeding/spotting occurred for 5 days or more, they were to remove the ring for 4 days, store it, and then reinsert that ring. RESULTS: Sixty-five women completed the continuous phase with reduced average flow scores in the continuous phase compared with the 21/7 phase (P<.02). Most patients had no to minimal bleeding during continuous use, with group 2 experiencing a statistically greater percentage of days without breakthrough bleeding or spotting (95%) compared with group 1 (89%) (P=.016). Instituting a 4-day hormone-free interval was more (P<.001) effective in resolving breakthrough bleeding/spotting than continuing ring use. CONCLUSION: A reduction in bleeding occurred during continuous use with replacement of the transvaginal ring compared with baseline 21/7 use. Continuous vaginal ring use resulted in an acceptable bleeding profile in most patients, reduction in flow, reduction in pelvic pain, and a high continuation rate.     

Bleeding patterns after immediate initiation of an oral compared with a vaginal hormonal contraceptive

OBJECTIVE: This study compared 84-day bleeding patterns after immediate initiation of a triphasic oral contraceptive with a 25-mug daily dose of ethinyl estradiol (E2) compared with the contraceptive vaginal ring, which has a 15-mug daily dose of ethinyl E2. METHODS: This was an open-label controlled trial. We randomly assigned 201 women to immediate start of a contraceptive pill or immediate start of the ring in a 1:1 allocation ratio. Our primary outcome was difference in mean bleeding-spotting days per woman according to treatment assignment. Secondary outcomes were differences in World Health Organization-defined menstrual indices, differences in perceived bleeding changes, and differences in bleeding according to cycle day at the start of method. RESULTS: The mean bleeding-spotting days in the 84-day reference period for all subjects was 19.2 days (17.0 days for ring users and 21.4 days for pill users, mean difference 4.4 days). Using the World Health Organization menstrual indices, the ring users experienced fewer days or episodes of bleeding-spotting and shorter intervals. Among ring users, no baseline characteristics were associated with bleeding outcomes. Older nulliparous pill users, however, reported more bleeding-spotting days. Significantly more ring users reported a decrease in duration of bleeding compared with pill users (P < .01). We found no significant differences in bleeding patterns based on analysis of cycle day at study enrollment. CONCLUSION: Our study shows advantageous bleeding patterns for subjects using the contraceptive vaginal ring. It also confirms our previous findings that immediate start of hormonal contraception is an acceptable alternative to waiting for menses. LEVEL OF EVIDENCE: II-1.     

Heavy menstrual bleeding

Heavy menstrual bleeding is defined as excessive menstrual blood loss which interferes with the woman's physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. All interventions should aim to improve quality of life rather than focussing on menstrual blood loss alone. An accurate history may indicate the cause of the bleeding. Indications for endometrial biopsy include persistent intermenstrual bleeding as well as heavy menstrual bleeding, in women aged 45 and over and those where there is evidence of treatment failure. First line treatment includes tranexamic acid or non-steroidal anti-inflammatory drugs or combined oral contraceptives.Second line treatment options include, levonorgestrel-releasing intrauterine system (provided long-term use is anticipated), oral norethisterone or injectable long-acting progestogens.In women with HMB alone who have failed to respond to the above treatment options: with uterus no bigger than a 10-week pregnancy, endometrial ablation should be considered in preference to hysterectomy. Where hysterectomy is indicated, the route of hysterectomy should be considered in the following order: first-line vaginal; second-line abdominal/laparoscopic.     

Menstrual bleeding, hormones, and the menopausal transition

The perimenopause represents a time of great variability in reproductive hormone dynamics and menstrual cycle characteristics, but age-related changes begin prior to this. These changes include a gradual increase in follicle stimulating hormone (FSH) levels, a gradual shortening of mean cycle length, and a decline in the number of ovarian follicles. The onset of perimenopause is thought to occur with the first break in menstrual cycle regularity. With the onset of cycle irregularities, hormone concentrations exhibit large increases in variability and unpredictability, rather than following a gradual trend with the approach of menopause, the final menstrual period. Abrupt spikes in gonadotropins and considerable fluctuations in estradiol and inhibin levels have been observed. Variability is the norm in the perimenopause, with hormonal fluctuations contributing to the visible signs of menstrual cycle and bleeding irregularities. To date there is no single endocrine indicator to serve as an adequate marker of menopausal status. This paper provides a review of research to date on patterns of reproductive hormones and menstrual bleeding during the menopausal transition. An understanding of such patterns can contribute to a better ability to distinguish "normal" transitional events from more serious pathology.     

Measured menstrual blood loss in women with a bleeding disorder or using oral anticoagulant therapy

Bleeding disorders in women are associated with a high incidence of menorrhagia, but few objective data exist. Whether oral anticoagulant therapy in women is also associated with a higher incidence of menorrhagia is unknown. We measured menstrual blood loss in six women with various congenital or acquired bleeding disorders and in 11 women treated with oral anticoagulant therapy. Mean menstrual blood loss in women with a bleeding disorder was 219 ml (range, 60 to 568 ml); five women had menorrhagia. In women treated with oral anticoagulant therapy, mean menstrual blood loss was 98 ml (range, 9 to 239 ml), and five women had menorrhagia. Of the six women with normal menstrual blood losses, two had losses in the high normal range (60 to 80 ml). No correlation existed between anticoagulant state and menstrual blood loss. The data support the close association between bleeding disorders and menorrhagia and suggest that oral anticoagulants increase menstrual blood loss.     

Abnormal uterine bleeding in adolescents

Abnormal and irregular bleeding are extremely common in the adolescent period and can be looked upon as a part of normal reproductive development. It is essential to have a firm grasp on the normal, physiologic development of the menstrual cycle. Prompt recognition and treatment of the situations that may indicate underlying disorders or diseases is possible. It is important to recognize the distinct needs, goals, and developmental stages of adolescent patients. No single therapy or approach is universal in the diagnosis and treatment, but must be tailored to the needs of the individual adolescent and her situation.     

The pathology of dysfunctional uterine bleeding

The mechanism of dysfunctional uterine bleeding remains unknown. Recent studies suggest that the majority of cases of dysfunctional uterine bleeding are due to local endometrial, or myometrial, dysfunction. Changes in the pattern of production of prostaglandins PGE2, PGF2 alpha, prostacyclin and thromboxane and increased fibrinolytic activity in the endometrium have been implicated in this disorder. Successful treatment of excessive menstrual bleeding with the prostaglandin synthetase inhibitor mefenamic acid and the fibrinolytic inhibitors epsilon amino caproic acid and tranexamic acid further substantiates the role of prostaglandins and fibrinolysis in pathological menstruation. The relationship between uterine mast cells, heparin-like activity and menstrual bleeding still needs to be elucidated. Further studies are required to improve our understanding of the pathogenesis of dysfunctional uterine bleeding, so that advances can be made in a specific treatment to restore normal menstrual function.     

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.     

Relief of uterine bleeding by cyclic administration of dienogest for endometriosis

Objective: This study assessed the relief of uterine bleeding and clinical symptoms during cyclic administration of dienogest for the treatment of endometriosis.

Methods: In total, 25 patients undergoing ovarian cyst enucleation and given dienogest participated in this study. Dienogest 2?mg/day was administered for 3 weeks, and the drug was then withdrawn for 1 week (cyclic administration of dienogest). This 4-week cycle was repeated six times. Patients’ records were prospectively analyzed for the number of days on which any uterine bleeding occurred, as well as menstrual pain before and after the start of dienogest administration were evaluated with a view to using the data obtained herein as the basis.

Results: During the period of cyclic administration of dienogest, uterine bleeding occurred on 5.8 to 7.7 days per 4-week period on an average through cycles. Of uterine bleeding episodes, menstruation-like uterine bleeding was present in about 80% of patients. The visual analog scale (VAS) value for menstrual pain significantly decreased from 3.8 before dienogest administration after surgery to 1.5 at the completion of cycle 1, VAS remained low thereafter.

Conclusion: These results raise the possibility that cyclic administration of dienogest may relieve lessen uterine bleeding, a major adverse event and menstrual pain.     

Abnormal bleeding in adolescents

Abnormal bleeding is a common clinical problem in adolescents, with the vast majority of cases resulting from anovulatory menstrual cycles. Although most episodes of abnormal vaginal bleeding do not cause acute medical complications, bleeding can be traumatic for young patients and their families. Health care providers with a solid knowledge of menstrual physiology and a thorough approach to differential diagnosis can evaluate and appropriately manage adolescents. In this article, we review the maturation of the hypothalamic ovarian axis, the most frequent etiologies of abnormal bleeding, as well as other less common causes and discuss diagnosis and treatment modalities.     

The influence of method of contraception and cigarette smoking on menstrual patterns

Summary. Self-perceived menstrual patterns have been investigated in a sample of 2115 women aged 18–9 years using a postal questionnaire. Seven aspects of 'abnormal' menstruation were denned: prolonged periods, heavy periods, frequent periods, irregular periods, intermenstrual bleeding, painful periods and severe premenstrual syndrome. Women who used oral contraceptives were less likely than other women to report any of the seven menstrual abnormalities except for intermenstrual bleeding and severe premenstrual tension. Women who used an intrauterine contraceptive device (IUCD) reported prolonged, heavy, and frequent periods and intermenstrual bleeding more often than other women, but they did not report painful periods with undue frequency. Women who had had a tubal sterilization generally reported menstrual patterns similar to, or slightly less favourable than, women using no contraception or contraceptive methods other than the pill or the IUCD. There was a significant association between smoking habits and each of the abnormal menstrual patterns except for severe premenstrual tension. In every case, the effect of smoking was unfavourable and in almost every case, current smokers reported the worst experience, with ex-smokers occupying an intermediate position. We believe that these data are of considerable clinical significance and that they offer a basis for a conservative approach to managing menstrual disorders in some women.     

The influence of method of contraception and cigarette smoking on menstrual patterns

Self-perceived menstrual patterns have been investigated in a sample of 2115 women aged 18-49 years using a postal questionnaire. Seven aspects of 'abnormal' menstruation were defined: prolonged periods, heavy periods, frequent periods, irregular periods, intermenstrual bleeding, painful periods and severe premenstrual syndrome. Women who used oral contraceptives were less likely than other women to report any of the seven menstrual abnormalities except for intermenstrual bleeding and severe premenstrual tension. Women who used an intrauterine contraceptive device (IUCD) reported prolonged, heavy, and frequent periods and intermenstrual bleeding more often than other women, but they did not report painful periods with undue frequency. Women who had had a tubal sterilization generally reported menstrual patterns similar to, or slightly less favourable than, women using no contraception or contraceptive methods other than the pill or the IUCD. There was a significant association between smoking habits and each of the abnormal menstrual patterns except for severe premenstrual tension. In every case, the effect of smoking was unfavourable and in almost every case, current smokers reported the worst experience, with ex-smokers occupying an intermediate position. We believe that these data are of considerable clinical significance and that they offer a basis for a conservative approach to managing menstrual disorders in some women.     

Frequency of spontaneously occurring postmenopausal bleeding in the general population

BACKGROUND: To determine the frequency of spontaneously occurring postmenopausal bleeding in the population, a prospective observational population study was undertaken. METHODS: Out of a population-based sample of 2000 Danish women aged 45-54 years, 1616 women responded to an initial questionnaire. Of these, 1059 women with natural gynecologic functions were eligible for the diary study, and of these, 951 (89.8%) women completed 1 year of daily recording of bleeding, medication relevant to bleeding, and medical consultations for gynecologic matters. Of the 951 women, 271 were postmenopausal. MAIN OUTCOME MEASURES: Occurrence of spontaneous postmenopausal bleeding including strength and length of each bleeding. RESULTS: Of 271 postmenopausal women, 29 (10.7%, 95% confidence interval 7.3-15.0%) recorded spontaneous postmenopausal bleeding. The incidence of women with bleeding was strongly correlated with time since menopause (P = 0.0001), with an estimated incidence of 409/1000 (218/1000-771/1000) person-years immediately after the first 12 months of amenorrhea following the menopause falling to 42/1000 (17/1000-102/1000) more than 3 years after menopause. CONCLUSIONS: This study indicates that recurrence of bleeding is very common in the time immediately after the 12 months of amenorrhea after what is currently defined as the final menstrual period, declining to low frequencies more than 3 years after the final menstrual period.     

The significance of bleeding patterns in Norplant implant users

The purpose of this study was to examine the bleeding patterns of 234 Norplant users during 5 years of use and to identify the bleeding patterns of users who conceived. During the first year of use, 26.6% of users had regular bleeding cycles, 66.3% had irregular cycles, and 7.1% were amenorrheic. By the fifth year of use, 62.5% of users had regular cycles, 37.5% had irregular cycles, and none had amenorrhea. Of the ten users who became pregnant, eight had regular menstrual cycles in the 6 months before the diagnosis of pregnancy, one had an irregular pattern, and one did not keep a bleeding record. None had amenorrhea. The 5-years cumulative pregnancy rate for patients with regular cycles was 17.4%; this was significantly higher (P less than .05) than the 5-year cumulative rates of 4.4% in users with irregular cycles and 0% in users with amenorrhea. This study indicates that during the first year of Norplant use, only 26.6% of users have regular cycles, but after the first year, 50-60% of users develop regular cycles. The bleeding patterns of women using Norplant improve after the first year of use, and those with regular cycles are at greatest risk for method failure.     

Abnormal uterine bleeding and underlying hemostatic disorders: report of a consensus process

An ad hoc consensus group determined that the prevalence of von Willebrand's disease in females with heavy menstrual bleeding is approximately 13%, but the severity of the disorder varies and, consequently, the overall clinical impact remains unknown. Consensus recommendations are presented, which include [1] a structured history for screening females with heavy menstrual bleeding; [2] a collaborative, multidisciplinary evaluation, and [3] a strategy for future basic science and clinical investigation.