New Treatment Approaches for Premenstrual Disorders | Page 2

Published Online: December 01, 2005
Andrea J. Rapkin, MD

Recently, several studies have assessed the efficacy of a new OC formulation containing EE 20 μg and drospirenone 3 mg (20EE/drospirenone) administered for 24 days, followed by a 4-day hormone-free interval (24/4), in the treatment of PMDD. Yonkers and Foegh reported on a double-blind, placebo-controlled, crossover study of 20EE/drospirenone that consisted of two 3-cycle treatment periods separated by a washout cycle.38 Of the 64 women, aged 18 to 40 years, with PMDD symptoms who were randomized, 34 women initiated active treatment with 20EE/drospirenone followed by placebo, and 30 women initiated placebo followed by the new OC formulation. The change from baseline with drospirenone/20EE was significantly superior to that with placebo in the DRSP, which was the primary outcome measure, and in the secondary outcome measures (ie, the CGI-Efficacy and CGI-Severity indexes), the self-rated rating scale for premenstrual tension syndrome (PMTS), and the Endicott Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) items 1 to 14 and item 16 (Table 5).

Figure

More recently, Yonkers and colleagues conducted another double-blind, placebo-controlled, parallel-group study with 20EE/drospirenone used in a 24/4 regimen in women with PMDD symptoms.39 The study design consisted of 2 run-in menstrual cycles (the qualification phase) followed by 3 treatment cycles. Of the 449 women who were randomized, 231 were in the active-treatment group and 218 received placebo. The primary outcome measure was the 21 individual items in the DRSP. When these individual items were grouped into physical, mood, and behavioral symptoms, 20EE/drospirenone was observed to be statistically superior to placebo for all symptom groupings. Improvement occurred as early as cycle 1 and continued during all 3 cycles. In addition, 20EE/drospirenone was significantly more effective than placebo in the observer- rated (P = .023) and self-rated (P = .004) rating scale for PMTS, the observer-rated (P = .004) and self-rated (P = .014) Clinical Global Impression (CGI)-Improvement scales, the 3 functional items of the DRSP (productivity and enhanced enjoyment in social activities, both P = .003; better quality of relationships, P = .0003), and the Q-LES-Q, items 1 to 14 (P = .05). (All P values have normality correction.)

One means of assessing the effects of various agents on premenstrual symptoms is to compare response rates using the same definition. For example, response rate was defined as a score of "much" or "very much" improved on the CGI-Improvement scale in 2 studies of the SSRI sertraline and in the crossover and parallel studies of 20EE/drospirenone 24/4. In a double-blind study, women with PMDD were randomized to a flexible daily dose (50-150 mg/day) of sertraline (n = 121) or to placebo (n = 122).40 At end point, 62% of the women in the active-treatment group and 34% of the women in the placebo group were classified as responders (P <.001). In a study of intermittent sertraline, the response rate was 58% in the women receiving active treatment and 45% in the placebo group (P = .036).41 The response rates in these 4 studies are compared in Figure 3.

Figure

Counseling Women With Premenstrual Disorders

To provide effective counseling for a woman with bothersome or severe premenstrual symptoms, physicians must be empathetic and caring communicators as well as knowledgeable about this complex area of women's health. It is important to assure the patient that her symptoms are real, with a physiologic basis, and that she is not "crazy."42 The clinician or other counselor should explain the details of the menstrual cycle to the patient, especially how premenstrual symptoms occur on a cyclic basis. Because patients usually retain only part of the information they receive during a visit, physicians should provide them with interesting and practical educational materials to reinforce what is discussed. Patients should keep a daily symptom diary for at least 2 months to ensure that an accurate diagnosis of PMS or PMDD is achieved. Clinicians or other counselors should provide the diary for prospectively recording the patient's symptoms, making certain that she knows how to use it properly.

Even before a diagnosis of PMS or PMDD has been made, the physician or counselor can help the patient identify ways to adjust her lifestyle to manage stress that can contribute to premenstrual symptoms. Patients should be encouraged to seek nonthreatening support from family and friends. In addition, they should be instructed about how to initiate lifestyle modifications, such as exercise, dietary changes, appropriate use of vitamin and mineral supplements, and stress management, including relaxation and cognitive behavioral approaches. Available pharmacotherapeutic options should be discussed, keeping in mind the patient's personal preferences, side effects, the cost of the treatments being considered, and her needs. For example, use of an OC might be the best first-line treatment choice for a woman who also has contraceptive needs, which can be reversed if so desired. OCs also have noncontraceptive health benefits of which the patient should be informed. Finally, the patient should be assured that she can try different therapeutic options until she finds the one most suitable for her.

Conclusion

A variety of approaches have been used to treat premenstrual symptoms. Lifestyle modifications, such as regular physical activity and dietary/nutritional changes, can reduce premenstrual symptoms in some women. Nonpharmacologic options are the easiest forms of treatment to implement, based on appropriate counseling, and can be tried by any woman as she charts her symptoms in a daily symptom record for at least 2 cycles to enable her physician to arrive at a correct diagnosis.

Several pharmacologic options have been shown to be effective and should be evaluated in light of the patient's individual needs and preferences. Some agents, such as particular SSRIs, are effective in many patients but also can be expensive and cause unwanted side effects. Other options, such as GnRH agonists, may be of limited use for similar reasons. Combination OCs are often used to treat premenstrual symptoms, even with a lack of evidence-based support, although new research is revealing more supportive data. OC formulations containing progestin drospirenone have been shown to be effective in treating symptoms of PMDD in controlled studies.

Counseling women about the nature of their symptoms and the variety of treatment possibilities provides much-needed reassurance in many instances and makes it feasible to individualize therapy based on the patient's preferences, treatment cost, and the most likely means of restoring patient comfort, function, and overall health.




Address correspondence to: Andrea J. Rapkin, MD, David Geffen School of Medicine at UCLA, Department of Obstetrics and Gynecology, 10833 Le Conte, Room 27-165 CHS, Los Angeles, CA 90095-1740; arapkin@mednet.ucla.edu.


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