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Hormorial Therapy in the Management of Premenstrual Syndrome

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Hormorial Therapy in the Management of Premenstrual Syndrome J Am Board Fam Pract: first published as 10.3122/15572625-11-5-378 on 1 September 1998. Downloaded from MEDICAL PRACTICE Hormorial Therapy in the Management of Premenstrual Syndrome Jeffrey D. Tiemstra, MD, and Krishna Patel, PharmD Background: Premenstrual syndrome (PMS) is characterized by any of a number of physical and psychological symptoms consistently occurring in the late luteal phase. Progesterone therapy is often recommended based on anecdotal evidence, although controlled studies have shown it to be ineffective. Oral contraceptives are more often used with mixed results. When hormonal therapy for PMS is indicated, the most appropriate choice remains a challenge. Methods: We describe a case report of successful hormonal therapy for PMS and a review of the literature on the effectiveness of hormonal therapies. Results and Conclusimls: Estrogen is clearly effective in relieving 'symptoms of PMS, whereas progesterone is ineffective and might even worsen symptoms. Combination oral contraceptives are effective, undoubtedly as a result of the estrogen component. While little comparative data exist to guide choice of an oral contraceptive, maximizing the relative estrogenic potency of the oral contraceptive seems logical. Depressive symptoms might not respond to hormonal treatment, and new research suggests that selective serotonin reuptake inhibitors might be particularly effective. 0 Am Board Pam Pract 1998;11:378-81.) Premenstrual syndrome (PMS), also referred to as elimination of caffeine, biofeedback, and relaxation late luteal phase dysphoric disorder, is a problem therapy. Because the beneficial effects of these copyright. commonly encountered in primary care, with up measures have not been proved, patients who seek to 10 percent of women of childbearing age experi­ medical attention for this syndrome will usually re­ encing symptoms severe enough to seek medical quire pharmacologic treatments. Patients with few treatment. I Despite decades of research, standard or closely related symptoms might benefit from criteria for the diagnosis of PMS are still debated. medication targeted at those symptoms. For in­ PMS can include any number of a wide variety of stance, headaches, cramping, and abdominal pain symptoms, such as depression, mood lability, can benefit from nonsteroidal anti-inflammatory swelling, abdominal pain, breast tenderness, drugs; abdominal bloating and leg edema will re- ' headaches, or fatigue. Although the constellation spond to loop diuretics; severe emotional symp­ http://www.jabfm.org/ of symptoms will vary from patient to patient, toms will respond to antidepressants or anxiolytics; characteristic of PMS is the timing of symptoms and migraine-type headaches can respond to mi­ around the menstrual cycle: symptoms predictably graine prophylactic or abortive therapy. Neverthe­ occur during the luteal phase, subside with menses, less, many patients either have too many symp­ and are absent during the follicular phase. toms to be targeted individually or have systemic Management of this common syndrome re­ symptoms such as fatigue for which there is no on 25 September 2021 by guest. Protected mains a challenge because many popular treat­ specific therapy.2-4 ments are unproved or known to be ineffective. As a result of the temporal relation of PMS to NOflpharmacologic recommendations often in­ the menstrual cycle, much attention has been given clude high-carbohydrate diets, vitamin and min­ to estrogen and progesterone treatment, with the eral supplementation (particularly pyridoxine), expectation that the entire array ofPMS symptoms might respond. Results have been mixed, however, and misconceptions persist among both patients Submitted, revised, 24 Sept 1997. From the Family Practice Residency, Saint Joseph Medical and providers regarding the relative efficacies of Center (JDl),Joliet, and the Departtnent of Phamlacy Prac­ estrogen and progesterone therapy. Specifically, tice, University of Illinois at Chicago (KP), Ill. Address reprint requests to Jeffrey D. liemstra, MD, Family Practice progesterone continues to be widely used in treat­ Residency, 24024 \Y. Brancaster Dr, Naperville, IL 60564. ment despite convincing evidence that it is not 378 ]ABFP Sept.-Oct.1998 Vol. 11 No.5 J Am Board Fam Pract: first published as 10.3122/15572625-11-5-378 on 1 September 1998. Downloaded from beneficial, whereas estrogen remains underrecog­ ual patients neither the timing nor the severity of nized as effective therapy. The following case illus­ symptoms correlated with fluctuations in hormone trates some of these pitfalls. levels.5,6 A 1991 study confirmed that variations in hormone levels did not correlate with symptoms, Illustrative Case and additionally found that pharmacologically ter­ A 38-year-old woman came to the office for man­ minating the luteal phase did not prevent the nor­ agement of PMS symptoms. The patient de­ mal cyclic appearance ofPMS symptoms.7 Thus scribed fatigue, sore throat, cold sores, myalgias, although PMS symptoms correlate with the late and ,chills starting in the week before her men­ luteal phase of the menstrual cycle, luteal phase strual period and peaking in the first 2 days of her levels of estradiol and progesterone do not appear period. By days 3 and 4 her symptoms completely to be direct causative factors. resolved, and she would feel fine for the next 2 to More recent hypotheses on the cause of PMS 3 weeks. She specifically denied headaches, bloat­ suggest a role for fluctuating levels of neurotrans­ ing, swelling, or weight gain. Her menstrual flow mitters in the production of symptoms.8,9 Specifi­ was heavy (eight or more heavy pads) the first 3 cally, estrogen has been found to stimulate certain days, tapering within 3 more days. These symp­ populations of dopamine and serotonin receptors, toms had developed within the last 5 years; before the same receptors that are stimulated by selective that she had more severe cramping with her peri­ serotonin reuptake inhibitor (SSRI) antidepres­ ods but less severe systemic symptoms. During the sants. 1O In addition, antiestrogen drugs, such as ta­ past 3 years she had sought medical care repeatedly moxifen and progesterone, have been found to for this condition. Dietary modifications included stimulate PMS symptoms in susceptible patients. I I low-fat, high-complex-carbohydrate diet, elimina­ Thus, PMS symptoms appear to be mediated in tion of caffeine, and supplementation with a B­ the central nervous system, and declining levels of complex vitamin. Pharmacologic treatments had estrogen in the late luteal phase might indirectly included ibuprofen, naproxen, cyclic progesterone, contribute to the timing of their appearance. and most recently an oral contraceptive (Lo/Ovral) Because of the decline of both estrogen and copyright. for 3 months. None of these treatments had pro­ progesterone levels in the late luteal phase coinci­ duced any relief. dent with the timing of PMS symptoms, both have Recent evaluations had included physical exam­ been considered and studied as potential treat­ ination, pelvic sonogram, complete blood count, ments. New understanding of the role of neuro­ iron studies, monospot test, thyroid function tests, transmitters in PMS has helped explain what have and glucose tolerance tests, the results of which been in the past confusing and conflicting data. were normal. The patient's prescription for oral contracep­ Treatment http://www.jabfm.org/ tives was changed from a OJ-mg norgestrel/0.03- Progesterone estradiol combination (Lo/Ovral) to a 1.0-mg Anecdotal case reports suggested that progesterone norethindrone/0.05-mg mestranol combination might be of benefit in the treatment ofPMS. Con­ (Ortho-Novum 1150) to achieve greater estrogenic trolled studies, however, have consistently shown activity relative to progestational activity. WIth this no benefit from progesterone; in fact, several stud­ change the patient had complete resolution of her ies have found a worsening of symptoms with prog­ on 25 September 2021 by guest. Protected symptoms within 2 months and was very pleased esterone. 12-14 Unfortunately, it continues to be rec­ with the res'ult. ommended as an option worth trying. Case reports of responses to progesterone treatment are most Causes of PMS likely explained by the fairly high placebo response Because PMS symptoms are by definition tempo­ seen in many PMS studies (up to 50 percent),9 al­ rally related to the menstrual cycle, it seems logical though weak estrogenic effects of therapeutic doses that cyclic fluctuations in estrogen or progesterone of progesterone through peripheral conversion to would be causally related. Studies in the 1980s, estrogen are theoretically possible. however, found that estrogen and progesterone \Vith the increasing use of long-acting forms of levels of patients with PMS did not differ from progesterone for contraception (Depo-Provera, asymptomatic control patients, and that in individ- Norplant), physicians should be aware of the po- Hormonal Therapy for Premenstrual Syndrome 379 J Am Board Fam Pract: first published as 10.3122/15572625-11-5-378 on 1 September 1998. Downloaded from tential for these treatments to aggravate preexist­ effect will be more beneficial for PMS patients, ing PMS. Women with PMS symptoms of mood there are few data to guide the physician's choice of changes, food cravings, sleep disturbances, and a particular oral contraceptive. Studies looking at dysmenorrhea might experience worsening of monophasic and triphasic formulations individu­
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