(Published September 2004)

Using Extended Regimen Oral Contraceptives for Nonmenstrual Benefits

Beyond the obvious benefits of extended and continuous regimen oral contraceptive (OC) use to reduce bleeding, practitioners and patients are using OCs in this manner to relieve menstruation-related complaints, such as breast tenderness, bloating, headache, and premenstrual syndrome or premenstrual dysphoric disorder, as well as medical conditions such as endometriosis.

Extended Use to Reduce Hormone Withdrawal Symptoms

In a retrospective study by Patsy Sulak and colleagues, women with hormone withdrawal symptoms were counseled to extend the standard 21/7-day regimen to 6, 9, or 12 weeks or until breakthrough bleeding or spotting occurred.¹ Reasons for using an extended OC regimen included decreased symptoms of headache (35 percent), dysmenorrhea (21 percent), hypermenorrhea (19 percent), and premenstrual symptoms (13 percent). The remaining 12 percent listed convenience, endometriosis, and other menstrual-related problems, such as acne. This was the first large series of extended use of OCs among patients complaining of hormone withdrawal symptoms. The study yielded 7 years of follow-up data for 292 patients (92 percent of the original 318 patients).

Symptom Improvement and Quality of Life

As shown in Figure 4, in this nonrandomized series, 86 percent of women using the extended regimen and 41 percent using the 21/7-day regimen reported that their symptoms improved. Ninety-four percent of the women using the extended regimen and 43 percent using the 21/7-day regimen reported that their overall quality of life improved. A potential limitation of this uncontrolled series is that a charismatic physician who strongly supports extended OC regimens supervised the care of these women.

In the first few years of the study, after an extended cycle of use, patients were instructed to discontinue pill-taking for the standard 7 days; most elected to do so after a typical cycle of 12 weeks (median 9 weeks). Although extended use of OCs effectively delayed hormone withdrawal symptoms, subjects often experienced a recurrence of symptoms (headache, premenstrual symptoms) during the 7-day hormone-free interval. The investigators subsequently advised patients to shorten the hormone-free interval to 4–5 days, and many avoided withdrawal side effects. The investigators suggested that this practice may concurrently increase contraceptive effectiveness via enhanced ovarian follicular suppression.

Drospirenone Extended-Use Trial

In a 6-month prospective, open-label, observational trial conducted in Germany, 175 women who chose to take an extended regimen of 30 mg of ethinyl estradiol (EE) and 3 mg of drospirenone (marketed as Yasmin^® in the United States) for 42–126 days were compared with 1,221 women who took the same OC using the standard 21/7-day regimen.² The aim of the study was to determine whether taking the OC for an extended cycle would affect menstrual-related symptoms such as swelling of the extremities, body weight, breast tenderness, feeling of bloating, acne, dysmenorrhea, breakthrough bleeding, and withdrawal bleeding.

Of the women using the extended regimen, 49 percent experienced a reduction in edema and 2 percent experienced an increase in this symptom. This was in contrast to the women using the 21/7-day regimen, 34 percent of whom had a decrease and 3 percent had an increase in edema. This difference was significant between the groups at p < 0.001. Of women using the extended OC regimen, 50 percent had decreased breast tenderness and 5 percent had an increase in this symptom. In contrast, among women using the traditional regimen, 40 percent had decreased breast tenderness and 7 percent had an increase in this symptom (significant difference between groups, p = 0.046). Women using the extended regimen experienced a 0.57-kg mean decrease in weight, whereas those using the standard regimen had a 0.61-kg mean decrease, a difference that was neither clinically nor statistically significant between groups. A feeling of bloating improved among 37 percent of women on the extended regimen and 29 percent on the 21/7-day regimen, but there was no significant difference between groups.

At the start of the trial, 35 percent of the women using extended regimen OCs and 33 percent of women using the 21/7-day regimen reported moderate to severe skin problems. After 6 months of therapy, only 5 percent of women taking the extended regimen and 8 percent taking the 21/7-day regimen reported these problems. (Statistical testing was not reported by the authors for this comparison.)

After 6 months of therapy, 65 percent of women using the extended OC regimen and 50 percent using the standard regimen reported an improvement in dysmenorrhea, whereas 2 and 3 percent, respectively, reported worsening; these differences were statistically significant in favor of the extended regimen (p = 0.0016). Breakthrough bleeding occurred in 15 percent of subjects using the extended regimen and 6 percent using the 21/7-day regimen. Duration and severity of bleeding were similar between the two groups, but the number of total withdrawal bleeding episodes was less in the extended regimen group. (Statistical testing was not reported by the authors for these comparisons.)

Among women using the extended regimen, 85 percent reported that they felt better or much better after 6 months and 2 percent felt worse, compared with 66 and 3 percent, respectively, of women using the standard regimen (p < 0.0001). Ninety-seven percent of women using the extended regimen and 91 percent using the 21/7-day regimen said that they would recommend the preparation.

Oregon Continuous Use Trial

In a randomized study, Kwiecien et al. compared the use of a 20-mg EE/100-mg levonorgestrel pill (168 days without a pill-free interval) with standard use (six 28-day cycles).³ Subjects were asked to record subjective side effects on a daily basis. There were no significant differences between groups in regard to the incidence of nausea, depression, and premenstrual syndrome. However, subjects in the continuous group had significantly less bloating (mean = 0.7 days in the continuous group and 11.1 days in the cyclic group; p = 0.04) and less menstrual pain (mean = 1.9 days in the continuous group and 13.3 days in the cyclic group; p < 0.01) than those in the cyclic group. In addition, continuous users reported approximately half as many days of headache (mean = 3.1 days in the continuous group and 9.6 days in the cyclic group) and breast tenderness (mean = 2.6 days in the continuous group and 7.1 days in the cyclic group) as cyclic users over the 168-day study, although these differences were not statistically significant.⁴ Interestingly, although the number of headache days reported by users of standard cycles remained about the same during each month of observation, users of the continuous regimen reported successively fewer headache days for each cycle. Weight decreased slightly and skin satisfaction was comparable and high in both groups.

Treatment of Endometriosis-Related Pain

An open-label, 6-month, randomized clinical trial of 90 women with recurrent moderate or severe pelvic pain after conservative surgery for endometriosis was conducted in Italy.⁵ This study compared continuous use of an OC containing 20 mg of EE and 150 mg of desogestrel with oral cyproterone acetate, 12.5 mg/day. Both drugs substantially reduced dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain scores and significantly improved health-related quality of life, psychiatric profile, and sexual satisfaction.

In a separate prospective, self-controlled clinical trial of 50 women who had undergone conservative surgery for endometriosis in the previous year but continued to experience dysmenorrhea with conventional cyclic OC use, the same investigators looked at continuous use of an OC containing 20 mg of EE and 150 mg of desogestrel for 2 years.⁶ They found that continuous use significantly reduced the frequency and severity of dysmenorrhea, and 80 percent of the women were satisfied or very satisfied with the treatment.

References

1. Sulak PJ, Kuehl TJ, Ortiz M, Shull BL. Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am J Obstet Gynecol 2002;186:1142-1149.
2. Sillem M, Schneidereit R, Heithecker R, Mueck AO. Use of an oral contraceptive containing drospirenone in an extended regimen. Eur J Contracept Reprod Health Care 2003;8:162-169.
3. Kwiecien M, Edelman A, Nichols MD, Jensen JT. Bleeding patterns and patient acceptability of standard or continuous dosing regimens of a low-dose oral contraceptive: a randomized trial. Contraception 2003;67:9-13.
4. Jensen JT. Reducing symptoms through continuous dosing regimens of low-dose oral contraceptives. Presentation at special symposium on extended and continuous cycle oral contraceptives, 59th Annual Meeting of the American Society for Reproductive Medicine, San Antonio, Texas, October 2003.
5. Vercellini P, DeGiorgi O, Mosconi P, et al. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril 2002;77:52-61.
6. Vercellini P, Frontino G, DeGiorgi O, et al. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril 2003;80:560-563.