Manipulating Menstruation with Hormonal Contraception — what does the Science say?

Following is an article from Center for  Research.

ARTICLE | Manipulating Menstruation with Hormonal Contraception — what does the Science say? by Jerilynn C. Prior and Christine L. Hitchcock

The flood of recent articles and magazine reports and even books (1) about so-called “menstrual suppression” describe taking the Pill continuously or for longer than 21 days with seven days off. The advertising suggests that this is giving women a “choice” to do away with menstrual flow or menstrual problems. The Federal Drug Agency in the USA has approved one oral combined hormonal contraceptive to be taken in four extended cycles a year. Not only do these new ways of taking the Pill allow companies a new patent on old drugs, they make it likely that the market for these products will expand from those who want to control pregnancy to those who want to eliminate menstrual flow.

We have two fundamental concerns with extended and continuous combined hormonal contraceptives: the hype surrounding these new ways of taking hormonal contraceptives is focusing negative ideas about women by making normal menstruation into a problem; and the health implications of these more continuous ways of administering higher doses of estrogen and progestin are not yet known.

Menstrual cycles are one of the fundamental differences women have from men. Because menstruation is linked to women, it is associated with women’s continuing inferior social status. Drs. Coutinho and Segal wrote, “a human menstrual period is the result of failure…” (1). Our culture certainly sees menstruation as negative, a wound (2), something messy or dirty, and to be hidden (3), especially from men. In fact, a woman CNN reporter complained that all the men producers in her department were excited by the menstrual suppression “story” because this gave them, for whom such talk would normally be taboo, the opportunity to discuss it! We as women, however, tend to have mixed feelings about our periods. Although some women have difficult menstrual cramps, heavy flow and clots or unpredictable onset of flow, most of those are either evidence of abnormal menstruation occurring without ovulation or are highly treatable (see “Painful Periods”). Even teenaged girls who complain about the onset of periods are concerned when their friends get their periods first! Likewise, both women and physicians have mixed and often contradictory attitudes about elimination of menstruation (4). Have periods have become the latest of women’s “deficiencies”? Is having regular menstrual flow a “Pill deficiency disease?!” We noticed that all of the papers that described extended and continuous use of CHC were in favour of this—the majority of studies have obvious support from the company making the CHC.

How might longer schedules of combined estrogen-progestin contraceptives work?

Higher-than-normal estrogen and at least similar levels of progestins to the menstrual cycle progesterone levels are necessary to suppress the growth of ovarian follicles and release of an egg. Our own menstrual cycles, once they get established in our early 20s, are hard to suppress. Even the usual 7-day break from the Pill is associated with increases in brain and pituitary hormones that are trying to get follicles growing within the ovary—each of these follicles makes estrogen. Occasionally ovulation will also occur on the Pill or other CHC methods but pregnancy usually doesn’t happen because the uterine lining is not lush enough for a fertilized egg to get fixed in place and grow. Evidence says that some follicles grow and some ovarian estrogen is made despite taking the Pill every day (5).

The endometrial uterine lining grows thicker under the influence of estrogen and is made more mature and thinner with progesterone or progestin. The estrogen and lower dose progestin from the CHC, plus the estrogen from growing follicles, probably explains the spotting on the long-cycle and continuous Pill. Years ago, I tried to suppress periods for women who needed to avoid the blood loss of menstruation during a bone marrow transplant. Because bone marrow makes platelets that are necessary for blood to clot, the women were at risk of heavy bleeding during the six weeks that the new bone marrow was becoming established. I tried to use progestin to help them have a period (shed their uterine lining) before their platelets got low. As soon as they had flow, I started a moderate dose Pill that they had to take every day without a break until their new bone marrow was working and their platelets were normal. What I saw was that after about six weeks of continuous Pill use women began to spot. These were women who were sick, had lost weight, were nauseated and were scared—all of these were reasons why the brain would be less likely to try to stimulate a period. Yet, most began to bleed if we had to continue the Pill longer than a month and a half.

How safe are longer or daily combined hormonal contraception schedules?

Our second major concern is the safety of extended and continuous use of combined hormonal contraception. These new schedules are being presented and regulated in the USA as though their potential health risks were identical to the risks from today’s lower dose cyclic CHC agents with hormones taken for 21 days out of 28 (Standard CHC). Therefore, the standard CHC cycle has been used as a “control” for these longer hormonal schedules. None of the studies have compared the long or continuous use of hormonal contraception with normal or abnormal cycles in randomized (by a toss of a coin) and placebo-controlled (compared with a dummy pill or patch or vaginal ring) studies. Most of the studies are biased because women were previous users of CHC, and so women who didn’t feel well on CHC would have dropped out early and not been asked to participate in these studies.

So what are the health risks that may exist from longer or continuous use of combined hormonal contraception? Caution says we should remember the recent history of drugs and devices in women’s health. It would not be wise to ignore the disease and death caused by fads of former years including Thalidomide, DES, early high-dose oral contraceptives, the Dalkon shield and “hormone replacement therapy” as a preventative treatment for asymptomatic menopausal women. The risks from routine menopausal hormone therapy could have been, and were predicted (6), 10 years before the first results of the Women’s Health Initiative hormone therapy arms showed that this therapy caused more harm than good for women without symptoms (7;8).

Let’s start with the things we know about the standard Pill. Even the current “low dose” Pill containing less than 30 mg of ethinyl estradiol is four times higher (stronger) than the average estrogen in the menstrual cycle. We know that the lower the dose of the estrogen the lower the risk for blood clots, heart attacks and strokes. But the longer or continuous use of CHC means that women are getting 25 to 33 percent more estrogen hormone exposure. At the moment there are too few scientific studies to be sure that continuous CHC doesn’t increase the current danger of blood clots from the Pill and the eventual risk for breast cancer, for trouble getting pregnant when we want to, or increase osteoporosis and fractures.

New testing of the safety of long or continuous CHC use must compared this with what is normal and natural—the menstrual cycle. These new ways of taking the Pill should not be approved by government agencies unless they are shown to be safe compared with the untreated menstrual cycle!

Although we think of the Pill as safe, a 25-year study in over 45,000 British women, of whom half were on the Pill and half weren’t, showed that deaths from cancer of the cervix (mouth of the uterus) and from cardiovascular diseases (like blood clots, strokes and heart attacks) were significantly increased in women on the Pill (9). That study started when Pill hormones were about 5 times higher than they are today, but at its end Pill hormones were similar to those we use today. The overall death rate was similar between those on and not on the Pill because the Pill, although causing endometrial and heart/stroke deaths, prevented deaths from ovarian cancer (9). A recent careful combination of all studies since 1980 of cardiovascular and blood vessel diseases during current normal-cycle Pill use showed that even the lowest dose Pills cause a doubling of the risk for strokes and heart attack (10).

Another safety issue, especially when bleeding is unpredictable, is the risk for overgrowth of the lining of the uterus. If the endometrium is thicker, cells are growing (proliferation) and usually under the influence of estrogen. If progesterone or progestin levels aren’t high enough to slow that growth, there is a risk for endometrial cancer. A single 1-year study of the endometrial safety of long-cycle Pill use suggests that the lining usually becomes thin and inactive, although about 10% of endometrial biopsies show proliferation (Anderson 2005). Unfortunately, from an 8-year study of continuous menopausal ovarian hormone therapy, the lining was thin and inactive, no bleeding was happening and yet two of 41 women were found to have endometrial cancers (11).

The next safety question relates to breast cancer and continuous Pill use. We link breast cancer risk with estrogen therapy—there is a small increased risk with standard CHC use (12). What is important to remember is that the continuous Pill causes more days of higher-than-normal estrogen levels. We don’t yet have any research on the risks for breast cancer and the continuous CHC. However, the risks would likely increase based on the higher estrogen levels.

I believe that breasts need a monthly time of low estrogen levels. The normal menstrual cycle provides this “break from estrogen” during flow. Even on the standard 21-day CHC, with the usual 7-day break, breasts feel different—they feel woody and more lumpy than normal. I am sure that, without knowing, I could tell by the way her breasts felt, whether or not a woman was on the Pill. Normal breast tissue is soft and has some variable texture. Because of no break, about 20% of menopausal women will have troublesome breast tenderness on continuous ovarian hormone therapy (that has much lower estrogen levels than the Pill) (13). In my experience, that tenderness goes away with three to five days off estrogen each month.

What about safety for bones and osteoporosis? We know that estrogen or estrogen with progestin therapy in menopausal women prevents fractures (14). We have thought that the combined hormonal contraception would also prevent osteoporosis. And there are some studies, usually small, in older women and without good controls suggesting that is true. However, a few years ago we showed that premenopausal Canadian women ages 25-45 who had ever used the Pill had lower bone density levels than women who had never used the Pill (15). An earlier study showed that young women using the Pill didn’t gain bone normally (16). Two studies have shown that fractures are increased about 20% in women who have used the Pill compared with women who haven’t (17;18). Other more recent studies suggest that calcium therapy can prevent the bone loss caused by the usual 21-day CHC cycle in young women with diets that are poor in calcium (19). We haven’t been able to find any study of bone density changes or fractures in women using the long or continuous CHC.

Women who stop a standard 21-day pill can expect to wait about two months longer before becoming pregnant than those stopping barrier methods—the higher the estrogen dose, the longer the delay in recovery of fertility (20). It is likely that the younger the woman who uses continuous or long-cycle CHC will have more negative effects on her future fertility because she has likely never been pregnant and her system is just “learning” to be fertile. Because long and continuous CHC methods include 25-33 percent higher estrogen exposure, that would also suggest a further delayed return to fertility. We have not found any studies that have looked at how long it takes to get pregnant after stopping extended or continuous CHC.

In summary, we think that long-cycle and continuous CHC use is effective for contraception. However, we know that it is likely to cause more unexpected bleeding than usual and less expected flow. We have many unanswered questions about safety that the current studies compared with standard CHC schedules are not addressing. We are looking for a randomized, blinded, placebo-controlled comparison of continuous OC and untreated menstrual cycles.