Menstrual-Related Disorders By Courtney I. Jarvis, Pharm.D.; and Anna K. Morin, Pharm.D. Reviewed by Louise Parent-Stevens, Pharm.D., BCPS; and Katherine Hammond Chessman, Pharm.D., FCCP, BCPS, BCNSP Learning Objectives complaints that typically do not cause functional impair- ment. Symptoms can be categorized into four domains: 1. Classify bleeding patterns associated with abnormal somatic (e.g., mastalgia, bloating, body aches, headache); uterine bleeding and demonstrate an understanding affective (e.g., depression, irritability, anxiety, mood of different evaluation techniques. swings, feeling out of control); behavioral (e.g., reduced 2. Based on the patient’s type and severity of bleed- interest in usual activities, appetite changes, social with- ing, construct an appropriate management plan for drawal); and cognitive (e.g., difficulty concentrating, abnormal uterine bleeding. sleep disturbances). About 90% of women of childbear- 3. Develop a management plan including nonpharma- ing age report experiencing premenstrual symptoms cologic and pharmacologic therapy for symptoms sometime in their lives; this is known as menstrual associated with premenstrual syndrome. molimina. A smaller subset of women (20%) describe 4. Develop a management plan including nonpharma- severe symptoms of PMS that warrant treatment, and cologic and pharmacologic therapy for symptoms 3% to 8% of women receive diagnoses of a severe form of associated with premenstrual dysphoric disorder. PMS known as premenstrual dysphoric disorder (PMDD). 5. Design an optimal treatment plan, based on a woman’s signs and symptoms and including nonpharmacologic Etiology and pharmacologic approaches, for a woman present- The pathophysiology of PMS and PMDD is not well ing with polycystic ovary syndrome (PCOS). understood. Although no hormonal imbalance appears 6. Apply nonpharmacologic and pharmacologic to exist in women with PMS or PMDD, the cyclic nature approaches to improve the likelihood of conception of estrogen and progesterone production is thought to in a woman presenting with infertility secondary to trigger premenstrual symptoms. Increasing evidence PCOS. supports that reduced blood concentrations and trans- mission of serotonin in the brain are linked to several Premenstrual Syndrome/ symptoms of PMS, including poor impulse control, irritability, dysphoria, and appetite changes. Reduced Premenstrual Dysphoric Disorder concentrations of g-aminobutyric acid, altered adrener- Premenstrual syndrome (PMS) is a term used to describe gic receptors, and reduced opiate concentrations during a constellation of more than 200 reported premenstrual the late luteal phase are also potentially associated with Baseline Knowledge Resources The goal of PSAP is to provide only the most recent (past 3–5 years) information or topics. Chapters do not provide an overall review. Suggested resources for background information on these topics include: • Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit J, et al (Task Force on the Phenotype of the Polycystic Ovarian Syndrome of The Androgen Excess and PCOS Society). The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91:456–88. • Lobo RA. Abnormal uterine bleeding: ovulatory and anovulatory dysfunctional uterine bleeding, management of acute and chronic excessive bleeding. In: Katz VL, Lentz GM, Loba RA, Gershenson DM, eds. Comprehensive Gynecology. Philadelphia: Mosby Elsevier, 2007:915–32. PSAP-VII • Women’s and Men’s Health 77 Menstrual-Related Disorders at least five symptoms, with at least one being markedly Abbreviations in This Chapter depressed mood, anxiety, affective lability, or irritability. ACOG American Congress Often, somatic complaints accompany the mood-related of Obstetricians and symptoms. These luteal symptoms must be confirmed Gynecologists through daily symptom ratings during menstrual cycles. COC Combined oral contraceptive Unlike PMS, there is substantial impairment of personal FSH Follicle-stimulating hormone functioning, generally more in social than in occupa- GnRH Gonadotropin-releasing tional situations. Risk factors for PMDD include age in hormone the late 20s to mid-30s, a history of psychiatric disor- LH Luteinizing hormone ders or substance abuse, and a family history of PMDD. PCOS Polycystic ovary syndrome Epidemiologic studies have not consistently demon- PMDD Premenstrual dysphoric disorder strated an association with parity, menstrual cycle PMS Premenstrual syndrome characteristics, oral contraceptive use, or socioeconomic SSRI Selective serotonin reuptake and lifestyle variables including smoking. inhibitor In diagnosing PMDD, a comprehensive history and physical examination are required to exclude other causes of the emotional and physical symptoms. It is important the development of premenstrual symptoms. In addi- to distinguish the marked emotional symptoms observed tion, it has been postulated that lower concentrations of in PMDD from those observed in other major mood or allopregnanolone, a progesterone metabolite with ben- anxiety disorders because treatment may differ. Several zodiazepine-like effects, occur in the late luteal phase valid and reliable diagnostic instruments are available for in women with PMS and play a role in some men- the prospective recording of symptoms in women with strual-related symptoms such as anxiety, irritability, and PMDD. Using these tools, the diagnosis of PMDD is con- premenstrual epilepsy exacerbations. firmed if symptoms are absent during the follicular phase of the menstrual cycle, markedly increased during the Characteristics luteal phase, and associated with functional impairment. Premenstrual symptoms occur cyclically during the luteal phase of the menstrual cycle and resolve quickly Supportive Therapies within a few days of the onset of menses. Women seeking Women with mild to moderate PMS symptoms often do medical attention usually have several symptoms from not require pharmacologic treatment. However, because all domains; however, mood and behavioral symptoms of its impact on social functioning, treatment is often are the most distressing. Premenstrual symptoms usu- warranted in women suffering from PMDD. First-line ally begin in the early 20s, but medical attention often treatment options are primarily supportive. Second-line is delayed for as long as 10 years after symptoms begin. treatment options include selective serotonin reuptake Genetic factors appear to play a role because women inhibitors (SSRIs) and anxiolytics. Alternative options are whose mothers had PMS are more likely to develop PMS, various hormonal therapies and surgery. and higher concordance rates of PMS are observed in Supportive therapies are recommended for all women monozygotic twins. experiencing PMS or PMDD symptoms, including Diagnostic criteria for PMS set by the American dietary changes, exercise, cognitive behavior therapies, Congress of Obstetricians and Gynecologists (ACOG) calcium supplementation, and complementary and alter- state that at least one affective and one somatic symptom native medicine (discussed in the Dietary Supplements must be prospectively charted during the 5 days before chapter). These modalities may lessen mild to moderate menses onset and during the three previous menstrual symptoms. Dietary recommendations include premen- cycles. Symptoms must occur in the absence of pharma- strual decreases in caffeine, salt, and refined sugar intake cotherapy, illicit drugs, or alcohol; must cease within 4 and consuming smaller, more frequent meals to help days of menses onset; and must not recur until day 12 diminish irritability, insomnia, fluid retention, breast of the next menstrual cycle. Other diagnoses, includ- tenderness, bloating, and weight gain. Weak evidence sug- ing psychiatric and nonpsychiatric disorders, should be gests that an increase in complex carbohydrates decreases excluded. Most other chronic conditions will be appar- mood changes based on the theory that complex carbo- ent throughout the menstrual cycle; however, some may hydrates lead to an increase in tryptophan, a precursor to worsen cyclically because of hormonal fluctuations, serotonin production. Exercise may increase endorphins, making the diagnosis difficult. These conditions include and it has been shown to considerably improve mood and depression, seizures, headaches, asthma, rheumatoid decrease lethargy. Cognitive behavior therapy, including arthritis, irritable bowel syndrome, and diabetes mellitus. relaxation and sleep hygiene, may effectively treat phys- Premenstrual dysphoric disorder is the most severe ical and emotional symptoms and is most effective in form of PMS. Diagnostic criteria require the presence of women with severe symptoms. Alternative treatments Menstrual-Related Disorders 78 PSAP-VII • Women’s and Men’s Health such as reflexology, massage therapy, biofeedback, acu- and have no symptoms during the follicular phase. Semi- puncture, and light therapy may offer improvement in intermittent dosing, which involves a combination of symptoms such as anxiety, depression, pain, and fluid continuous daily SSRI dosing with increased dosages retention; however, evidence for the use of these strate- during the luteal phase, is appropriate for women who gies is limited and of low quality. experience mood symptoms throughout their menstrual cycle, with symptoms worsening during the luteal phase. Pharmacologic Treatment Dosing of SSRIs should be