Contraceptive redesign: new progestins/new regimens

Journal of Family Practice, Sept, 2004 by Patricia J. Sulak

Although oral contraceptives (OCs) have been in use for more than 40 years, side effects continue to affect compliance. (1) Thus, 2 questions must be asked: Is there a need for changes in traditional OC regimens? Can new regimens and/or new progestins provide additional benefits to patients?

As evidenced by recent studies, (2-6) new regimens that shorten the hormone-free interval and/or extend the duration of active-pill administration offer the potential to ameliorate side effects and to reduce or eliminate monthly bleeding. The findings of these investigations challenge the accepted 21/7-day regimen for OC administration and document the incidence of hormone-withdrawal symptoms induced by the current 21/7 design.

New progestins are also of potential significance. Until recently, all progestins used in OCs available in the United States were derived from 19-nortestosterone. A new OC uses the progestin drospirenone (DRSP), an analogue of spironolactone, which has different pharmacologic properties that may result in improved side-effect profiles and additional noncontraceptive benefits, some of which will be discussed in the article Management Strategies for PMS/PMDD by Dr Yonkers.

Because OCs have beneficial effects on health conditions associated with menstruation, they are often used to decrease bleeding and cramps and to ensure a predictable bleeding pattern. New regimens and/or agents may increase these benefits further.

21/7 REGIMEN: A HIGH INCIDENCE OF SIDE EFFECTS

Our group investigated the side effects associated with the standard 21/7-day OC regimen in a prospective study. We reported that this schedule of administration leads to many common menstrual complaints that occur during the traditional 7-day hormone-free interval: bleeding, cramps, and premenstrual symptoms (PMS) such as mood swings, breast tenderness, bloating/swelling, headaches, and the increased use of pain medications (TABLE 1). (7) It should be noted that the 21/7 schedule originally was developed to mimic the normal menstrual cycle and reassure women that they were not pregnant.

Furthermore, although OCs frequently are prescribed to treat pelvic pain and dysmenorrhea, the traditional 21/7 regimen has been shown to worsen such symptoms in many patients.

Numerous studies have evaluated the effect of altering the traditional 21/7 regimen, noting that the standard regimen does not provide health benefits, is not necessary from a health perspective, and often induces hormone-withdrawal symptoms. (2,8-14)

21/7 regimen often changed in clinical practice

Discussions with practicing gynecologists and nurse practitioners reveal that most clinicians have recommended an extended active-pill administration for those patients who desire less frequent bleeding or who experience bothersome withdrawal side effects, such as heavy bleeding, headaches, pain, or PMS.

Alterations in the 21/7 regimen have been well accepted by patients, as reported in several studies by our group, which will be described subsequently in this article. (2,14)

21/7 regimen and follicular growth

Physiologically, the standard 7-day hormone-free interval has been shown to permit follicular growth: Follicle-stimulating hormone levels increase on day 3 or 4, which allows for follicular recruitment and estradiol production. The 7-day interval also provides less ovarian suppression than is seen with shorter hormone-free intervals. (8,9)

If active pills are initiated after the 7-day hormone-free interval, the estrogen levels that have begun to rise will decline slowly over the next 2 weeks, reaching their lowest levels during the last week of active-pill administration. This may explain why, for women on OCs, withdrawal symptoms often begin during the last week of active-pill administration. (7) The 21/7 regimen increases the potential for follicular cysts. (8,9,15)

NONCONTRACEPTIVE HEALTH BENEFITS OF OC USE

The potential benefits associated with OC use are particularly significant with respect to modern women's reproductive patterns. It is generally acknowledged that, compared with earlier generations, women today experience menarche at an earlier age and postpone childbearing. Women also tend to have fewer children, breastfeed for a shorter period of time, and enjoy a longer life span. Thus, compared with their ancestors, women experience many more menstrual cycles and, therefore, a higher risk for menorrhagia, irregular bleeding, dysmenorrhea, PMS, menstrual migraines, and perimenopausal bleeding and symptoms.

OC use increasing among perimenopausal women

Over a lifetime, the menstrual patterns of contemporary women may increase the risk for conditions associated with menstruation such as anemia, endometriosis (along with pain and infertility), ovarian cysts, and ovarian cancer.

In this light, it may be significant that according to a 1995-2000 survey, an increasing number of women are using OCs, with the most significant increase among perimenopausal women. (16) Many women may use OCs for the noncontraceptive benefits rather than for the purpose of contraception.