Contraceptive Technology Reports: Examination of Extended Hormonal Contraception to Reduce Bleeding
Author: Andrew M. Kaunitz, MD, Professor and Assistant Chairman, Department of Obstetrics and Gynecology, University of Florida Health Science Center, Jacksonville.
Peer Reviewer: Michael Rosenberg, MD, MPH, President, Health Decisions, Chapel Hill, NC, Clinical Professor of Epidemiology and OB/GYN, University of North Carolina, Chapel Hill.
Frequent menstruation is a relatively new biologic state that has emerged as societies have evolved from hunting and gathering to industrialization. Contemporary American women will experience an average of 450 menstrual cycles over their lifetimes — nearly three times more than women living in primitive societies (160).1 This increased number of menstrual cycles is attributed to earlier menarche, later first birth, fewer pregnancies, shorter duration of breast-feeding, and later menopause.1
The burden of menstruation ranges from a monthly nuisance to a major health concern of women. The leading cause of gynecological morbidity in the United States, menstrual disorders affect 2.5 million women ages 18-50 annually and accounted for approximately 11% of hysterectomies performed in 1997.2,3 Menstrual disorders cost U.S. industry an estimated 8% of the total wage bill, and a 1999 survey found that U.S. women with heavy menstrual flow worked nearly 7% less time than those with lighter or normal flow.4,5
Medically reducing the frequency of menstruation holds the promise of decreasing the frequency of menstrual-related disorders such as menorrhagia (whether idiopathic or associated with uterine fibroids, adenomyosis, von Willebrand disease, Factor IX deficiency, hemophilia carrier state, or thrombocytopenia of any etiology), dysmenorrhea, iron deficiency anemia, and catamenial conditions (i.e., migraine headaches and seizures).6-9 Other chronic diseases that are exacerbated by menstrual cycles also might benefit from extended cycling.8,10 In addition to women with these disorders, others who might benefit from less frequent menses include adolescents, perimenopausal women, collegiate swimmers, female soldiers deployed to the desert, developmentally delayed women, and any woman who simply would prefer to menstruate less frequently.8,11-15
Several recent surveys reflect how women’s attitudes regarding monthly menstruation are changing as that option has become available. As part of a 1996 survey of Dutch women, 964 oral contraceptive (OC) users ages 15-49 years were asked what menstrual frequency they would prefer if able to regulate it.16 Overall, 75% of OC users preferred altering bleeding patterns for less painful periods, shorter periods, or less heavy periods. Seventy-two percent of OC users aged 15-19 years, 60% of those aged 25-34 years, and 59% of those aged 45-49 years preferred less frequent menstruation.
Another survey to assess the attitudes of Chinese, Nigerian, South African, and Scottish women toward amenorrhea and use of a contraceptive method that produces amenorrhea found that health care providers overestimate the importance women place on regular menstruation.17 With the exception of Black African women, more than half of the 1,001 women surveyed disliked having periods. Reasons cited for disliking periods included inconvenience (65%-85%) and, among Chinese and Scottish women, associated menstrual problems (13%-33%). In contrast to Nigerian women who preferred to bleed monthly, those in other countries preferred to bleed once every three months or not at all.
In the United States, the Washington, DC-based Association of Reproductive Health Professionals commissioned the Rochester, NY-based Harris Interactive to conduct a telephone survey of U.S. women regarding their preferences on frequency and characteristics of menstrual bleeding.18 Of the 491 women ages 18-49 included in the survey conducted in 2002, 44% stated that they would prefer never to menstruate, and this preference increased to 59% when only those aged 40-49 were analyzed.
Fewer than 30% preferred monthly menses. More than one in four women had missed professional, social, athletic, or family-oriented events because of their period, menstrual cramps, or other menstrual effects. Of the 70% of women who currently or previously used OCs, 15% stated that they had used their OC regimen to delay or stop their periods.
Another U.S. study to explore women’s attitudes and beliefs about menstruation and menstrual suppression also found that more than two-thirds of the 221 respondents ages 12-30 were interested in reducing menstrual pain and the amount of bleeding, particularly if they were not on hormonal contraception (48% of the sample population).19 When asked if it was necessary to have a period every month, 52% of those not on a hormonal method said "yes" compared with 37% of those currently using OCs. In fact, 45% of OC users and 32% of women not using a hormonal method thought that it was not necessary to have a monthly period. With regard to menstrual suppression, 57% of respondents strongly agreed or agreed that they were interested. Women currently using OCs were more interested in using a contraceptive for menstrual suppression than those not using OCs.
Hormonal Options for Reducing Menstruation
Several hormonal contraceptive options can reduce menstruation. (See Table 1.) A substantial proportion of women using an extended OC regimen or depot medroxyprogesterone acetate (DPMA) will be amenorrheic after one year’s use.20-22 Users of the levonorgestrel intrauterine device (LNG IUD) experience substantial reductions in menstrual blood loss, with 80% of users eventually becoming amenorrheic or oligomenorrheic.23,24 To date, there are no reports on extended use of the combination transdermal contraceptive patch or the contraceptive vaginal ring. However, the good cycle control observed in users of these methods suggests they may become attractive options for extended use, and clinical trials are in progress.25,26
Extended-Use OCs to Reduce Bleeding
When use of a progestational agent as a hormonal contraceptive was suggested in the 1950s, the regimen of 21 days of active drug followed by seven drug-free days was designed to mimic the normal menstrual cycle because of concerns that anything perceived to interfere with normal menses might be unacceptable to women, clinicians, and religious leaders.7 Gregory Pincus, PhD, John Rock, MD, and others who developed OCs understood that the monthly bleeding experienced by pill users was induced by hormone withdrawal and was not biological. During the past 40 years of OC use, many clinicians have come to appreciate that there is no evidence to support the perception that monthly bleeding contributes to the health or general well-being of women. As mentioned earlier, women themselves also are receptive of the idea of manipulating their hormonal contraceptive regimen to reduce or eliminate menstrual bleeding.16-19,27
Recent Studies of Extended Cycle or Continuous-Use OC Regimens. Recently, four open-label, randomized, controlled trials using monophasic OCs compared extended cycle or continuous regimens with a conventional 21/7 regimen.20,28-30 (See Table 2.) Two of these were small studies that compared a conventional 21/7 regimen of 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) used for six or 12 cycles with continuous use for 168 or 336 days, respectively.20,28 In the six-cycle study, women who used the OC continuously for 168 days experienced significantly fewer bleeding days requiring protection (< 2 vs. ~4 days, P < 0.01) and were more likely to be amenorrheic than those using the conventional OC regimen.28 Headache, breast tenderness, nausea, depression, and premen-strual syndrome (PMS) were reported with similar frequency in the two groups; however, compared to women using the conventional OC regimen, those in the continuous use group experienced significantly less bloating (mean 11.1 vs 0.7 days, P = 0.04) and menstrual pain (mean 1.9 vs. 13.3 days, P < 0.01) overall. The majority (70%) of women in each treatment group were satisfied with bleeding patterns. Moreover, in the continuous group, endometrial stripe measurements showed a reassuring mean thickness of 3.3 mm (SD = 0.73).
In the 12-cycle study, amenorrhea occurred in 16% and 72% of continuous OC users during cycles 1-3 and 10-12 compared to 0 and 4%, respectively, of those using the conventional OC regimen.20 Initially, spotting commonly was reported by those in the continuous group; however, by cycle nine, less spotting was noted in the continuous group than in the conventional OC group. There were no pregnancies, and no evidence of endometrial hyperplasia was observed. Breast tenderness and nausea were infrequent complaints in both groups. However, abdominal pain occurring at least once a month was reported by significantly fewer continuous OC users than conventional OC users who completed the study (26% vs. 72%, P < 0.001). At the end of the study, 78% of 32 continuous OC users and 68% of 28 conventional OC users chose to continue their present method.
Another small 12-month study compared a conventional 21/7 regimen and an extended 42/7 regimen of a monophasic OC containing 30 mcg EE/300 mcg norgestrel.29 The percentages of patients who completed the study were 63% in the extended cycle group and 54.5% in the conventional cycle group. The number of bleeding days was reduced significantly in the extended cycle group beginning in the first trimester (mean 6.4 vs. 10.9 days, P < 0.001), and this continued to the fourth trimester (mean 5.8 vs. 11.3 days, P = 0.005). The mean number of spotting days was similar in both groups throughout the study. Women in the extended cycle group had significantly fewer total days requiring use of hygiene products than those in the conventional group (27.3 vs. 53.5 days, P < 0.001), which corresponded to a lower average annual expenditure for hygiene products of $17.45 compared to $41.45 (P < 0.001). At the completion of the study, among women who planned to continue use of hormonal contraception, 52.4% of those in the extended cycle group planned to continue the regimen, and 16.7% of those in the conventional group planned to switch to an extended cycle regimen.
A large (N = 682), one year, multicenter study compared an extended 84/7 OC regimen provided in dedicated packaging (Seasonale) with a comparable conventional OC (Nordette); active pills of both contained 30 mcg EE/150 mcg LNG.30 The extended 84/7 OC regimen was as effective in preventing pregnancy as the conventional 21/7 regimen and was associated with a comparable amount and number of days of scheduled withdrawal bleeding. Although the frequency of unscheduled bleeding/spotting episodes was higher initially with the extended regimen, it declined over time. No endometrial hyperplasia was noted, and the nonmenstrual side effects reported by women using the extended-cycle regimen were comparable to those reported by users of the conventional regimen.
When suggesting extended OC use, it is important to explain that there is no medical rationale for monthly withdrawal bleeding while on hormonal contraceptives and that the conventional OC regimen arbitrarily was designed to mimic the natural menstrual cycle. Myths that hormonal methods are associated with a buildup of menstrual blood or disease of the lining of the uterus should be dispelled. Review the advantages of the extended regimen, particularly those that are most important to the individual patient. For example, painful periods, excessive bleeding, PMS, or menstrual-related migraines may be reduced by reducing the frequency of menses or eliminating the pill-free interval. Moreover, the regimen is convenient; bleeding can be postponed until after particular occasions such as vacations and athletic activities, and fewer hygiene products need to be purchased or carried. Patients should be prepared for the occurrence of unpredictable breakthrough bleeding similar to that with conventional OC regimens initially, which will lessen over time. Be sure to tell the patient that should she spot, the blood will be dark-brown rather than red because it has remained in the vagina longer and may have a different texture.
It may be more difficult for the woman using an extended OC regimen to tell if she is pregnant. She should be told to look for other signs of pregnancy such as breast tenderness, nausea, fatigue, or frequent urination, and she should be reassured that pregnancy tests can be performed if needed.
Surveys show that many women today would prefer to menstruate less. A variety of hormonal contraceptive options can reduce or eliminate menstrual bleeding, including DMPA, the LNG-IUD, and combination OCs. Experience with continuous or extended low-dose OC (£ 30 mcg EE) regimens indicates that they are as effective as a conventional regimen in preventing pregnancy and produce amenorrhea or infrequent bleeding in a majority of users. Extended OC use is not associated with endometrial hyperplasia and may help improve the health status of many women and, for even more, the quality of life.
As women and their clinicians become more familiar and comfortable with extended hormonal contraception to reduce menses, more women will choose to take advantage of this strategy. The result for some women will be enhanced convenience; others will experience a reduced burden of suffering from gynecologic and medical conditions.
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