Long OC and safety

In our review, we were also concerned about what research has been conducted on safety. Standard OCs are known to increase the risk of thrombosis (clotting), which can be very serious. In a large 25-year study of 46,000 women in the UK, Dr. Valerie Beral found that the use of oral contraceptives were associated with higher mortality from cerebrovascular events (such as stroke), and lower mortality from ovarian cancer and colorectal cancer. On balance, women who have used oral contraceptives had no higher mortality than non-users (Beral et al., 1999).

In addition to our interest in the standard risks of oral contraceptives, we also considered possible increased risks from Long OC. Long OC use results in a slightly higher total exposure to the high levels of estrogens in oral contraceptives. It also limits the amount of time that a woman's body is free from external hormones. In a normal menstrual cycle, there is a cycle between high estrogen exposure and a time of low estrogen exposure. Long OC reduces the time that a woman's breast tissue and endometrium are given a break from the high levels of estrogen.

Finally, oral contraceptives act by suppressing the complex and intricate hormonal feedback system between the hypothalamus, the pituitary and the ovary. They act at the level of the brain, preventing the signals that normally initiate follicular development and ovulation. Women who try to become pregnant after taking oral contraceptives take several extra months, on average, to become pregnant, when compared with women who stop using a barrier method (e.g., condoms or diaphragm) or an IUD (Bracken, Hellenbrand, & Holford, 1990). Higher dose oral contraceptives are associated with a longer delay to conception. Long OC has a slightly higher total dose of estrogen, but also has the potential to suppress the hypothalamic-pituitary-ovarian axis more strongly than Standard OC.

(Cachrimanidou et al., 1994) studied 13 women on Long OC (63/7) and 7 women on Standard OC to look at clotting factors and cholesterol. All of the women in her study were new users. There were no statistically significant differences in blood lipids (cholesterol, HDL, LDL) between the two groups. For the most part, blood lipids did not change across the year. Total cholesterol tended to rise across the year, and this increase was significant in the Long OC group. There was also an increase in the VLDL component of cholesterol after 3 months in the Standard OC group. There were increases in triglycerides under both OC regimens. Factors related to coagulation increased under both OC regimens, while coagulation inhibitors showed small decreases. This study demonstrates some of the physiological changes that may be associated with increased risk of clotting in OC users. Long OC users showed a non-significant tendency to be more affected than were Standard OC users.

We found no studies of breast or endometrial safety in these papers on Long OC. There are anecdotal reports of perhaps a dozen women among the various studies who discontinued Long OC and become pregnant. However, we did not find any systematic study of the return to fertility or normal ovulatory function following discontinuation of a Long OC schedule.

Long OC and menstrual taboos

Advocates of menstrual suppression with an extended schedule of oral contraceptives have several arguments. Some suggest that women might occasionally extend the number of active pills to delay menstruation on particular occasions. Some suggest that women taking oral contraceptives should have a choice about how frequently they menstruate. They often point out that the original schedule of oral contraceptive pills, 21 days of active pills followed by a seven day pill-free window (a 21/7 schedule, for short), was an arbitrary one, chosen in the vain hope that a normal menstrual pattern would render oral contraception acceptable to the Vatican.

Other advocates of menstrual suppression argue that fewer menstrual bleeds will result in less menstrual discomfort and premenstrual discomforts. Finally, some have suggested that unmedicated menstruation is itself unhealthy, and that extended use of oral contraceptives will improve women's health.

Menstruation is a taboo in our culture, and women who are menstruating take efforts to conceal the fact. Women differ in how they feel towards menstruation, and those women who find menstruation most distasteful and embarrassing are the women who are most interested in the use of Long OC for menstrual suppression. Women also vary in the amount of discomfort they experience with menstruation. In a study presented at the recent Society for Menstrual Cycle Research meetings, distaste was more important than discomfort in predicting women's attitudes to menstrual suppression with Long OC (Hoyt & Andrist, 2003).

Adolescents may be particularly vulnerable to Long OC. Having someone discover that you are menstruating is among the top mortifying moments that teenage girls share with magazine column writers (Houppert, 1999). Being able to avoid and control menstrual flow may become a status symbol as well as a convenience, adding peer pressure to the other reasons a young woman might use Long OC. A recent "how to" article for clinicians documents a variety of physical and social reasons to prescribe extended oral contraceptives to adolescents (Sucato & Gold, 2002). While the author states that there are no data on Long OC use by teenagers, she does not go so far as to urge caution, nor to comment that there are contraindications for oral contraceptive use on any schedule. The potential for harm from Long OC use is greater when taken by developing girls. It is common for there to be a vulnerable period during growth and development, and it is not known what effect extending the suppressive effects of oral contraceptives will have on a developing reproductive system. Risks must be weighted against benefits, and the prevention of pregnancy in a sexually active teenager is a greater benefit than the suppression of menstruation for convenience. Moreover, in general, Long OC for menstrual suppression is likely to be sought at a younger age than OC for contraception.

In the coming weeks and months, there will likely be much more media coverage of the idea of menstrual suppression with Long OC. There are research studies that have been conducted on Seasonale®, but the results of these studies have not yet been published. To date, the studies that have been published show that extending the number of active pills between pill free intervals decreases the amount of scheduled withdrawal bleeding, but increases the amount of unscheduled bleeding and spotting, compared with Standard OC schedules. New users have more problems than women switching from Standard OC to Long OC, and the amount of unscheduled bleeding becomes better with time. The primary reason for women to discontinue Long OC is dissatisfaction with the bleeding patterns.

In our review we found that, contrary to what has been commented on in the media, there are a number of important questions about the safety of using Long OC that have not yet been addressed. There are no published data on how an extended OC schedule affects the endometrium or breast tissue, and there are no systematic data on how long it takes women to return to normal ovulatory function or to become pregnant after stopping a Long OC regimen. Particularly for adolescents, it is important to confirm that the suppression of menstruation with Long OC is reversible and does not affect development. The fact that many women have been using Long OC for years suggests that there is no dramatic effect. However, we need systematic trials, not just testimonials and expert advice from clinicians who see a small number of women. Recent results from the Women's Health Initiative trial of estrogen-plus-progestin hormonal therapy amply demonstrate that randomized placebo controlled trials are required to test even the most firmly held and widespread beliefs about the benefits of preventive hormone therapy.

References

1. Beral, V., Hermon, C., Kay, C., Hannaford, P., Darby, S., & Reeves, G. (1999). Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46,000 women from Royal College of General Practitioners' oral contraceptive study. British Medical Journal, 318, 96-100.
2. Bracken, M. B., Hellenbrand, K. G., & Holford, T. R. (1990). Conception delay after oral contraceptive use: the effect of estrogen dose. Fertility & Sterility., 53(1), 21-7.
3. Cachrimanidou, A.- C., Hellberg, D., Nilsson, S., von Schoulz, B., Crona, N., & Siegbahn, A. (1994). Hemostasis profile and lipid metabolism with long interval use of a desogestrel-containing oral contraceptive. Contraception, 50 (August), 153-165.
4. Cachrimanidou, A.- C., Hellberg, D., Nilsson, S., Waldenstrom, U., Olsson, S.- E., & Sikstrom, B. (1993). Long interval treatment regimen with a desogestrel-containing oral contraceptive. Contraception, 48 (September), 205-216.
5. Houppert, K. (1999). The Curse: confronting the last unmentionable taboo: menstruation. New York: Farrar, Strauss and Giroux.
6. Hoyt, A., & Aandrist, L. C. (2003). Women's attitudes and beliefs about menstrual suppression. Society for Menstrual Cycle Research, Conference Presentation.
7. Miller, L., & Notter, K. M. (2001). Menstrual reduction with extended use of combination oral contraceptive pills: randomized controlled trial. Obstetrics & Gynecology., 98 (5 Pt 1), 771-8.
8. Sucato, G. S., & Gold, M. A. (2002). Extended cycling of oral contraceptive pills for adolescents. Journal of Pediatric & Adolescent Gynecology., 15 (5), 325-7.
9. Sulak, P. J., Cressman, B. E., Waldrop, E., Holleman, S., & Kuehl, T. J. (1997). Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms. Obstetrics & Gynecology, 89 (2), 179-83.
10. Sulak, P. J., Kuehl, T. J., Ortiz, M., & Shull, B. L. (2002). Acceptance of altering the standard 21-day /7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. American Journal of Obstetrics & Gynecology, 186 (6), 1142-9.