COMMENTARY

An Update on Premenstrual Disorders: Diagnosis and Management

Peter Kovacs, MD, PhD

Disclosures

May 07, 2018

Hormones and the Menstrual Cycle

The menstrual cycle is accompanied by characteristic hormonal changes.[1] As the activity of the corpus luteum declines, the pituitary release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increases, and a new cohort of follicles will progress towards ovulation. Eventually a single follicle emerges as the dominant follicle. The follicular phase is characterized by estradiol dominance. Following ovulation, the steroidogenic activity of the follicle (now called corpus luteum) changes too. Although estradiol is still produced, progesterone takes over as the dominant hormone of the luteal phase. This all prepares the endometrium for implantation, but because steroid receptors can be found in many organ systems, the cyclic hormonal changes affect other organs as well.

Progesterone relaxes smooth muscles and therefore slows down bowel function, leading to constipation and bloating. Steroid receptors can be found in the brain as well, and those who are particularly sensitive to hormonal fluctuations often complain about mood changes, such as irritability and anxiety, during the luteal phase. In some cases, the symptoms can be so dominant that they interfere with routine daily activity and influence overall quality of life.

Premenstrual Disorders: Diagnosis and Management

A recent review by Yonkers and Simoni[2] discusses the diagnosis and treatment of premenstrual disorders.

Premenstrual disorders are characterized by physical or emotional symptoms that recur in the luteal phase of the menstrual cycle and which resolve with the onset of menstruation. Premenstrual symptoms clearly show an association with ovarian steroids because they do not affect women before menarche or after menopause. The diagnosis can be established when physical or affective symptoms occur in the second half of the cycle and resolve with menstruation.

Premenstrual physical and affective symptoms may vary in intensity. The more severe premenstrual dysphoric disorder (PMDD) is a well-established clinical syndrome. It is believed that women with premenstrual symptoms or PMDD display an abnormal response to progesterone, progesterone withdrawal, and progesterone metabolites. The response is thought to be mediated by altered serotonin transmission.

The most common symptoms are bloating, mood swings, lethargy, irritability, anxiety, and breast tenderness. Premenstrual symptoms affect up to one third of women, whereas PMDD affects only 1%-6% of women.[2] Symptoms are more common among white women, those with higher body mass index, and smokers.

Premenstrual disorders need to be differentiated from random symptoms that may fall into the luteal phase or from constant symptoms that exacerbate in the luteal phase. Documenting the symptoms for two or more cycles may help the diagnosis. It is reasonable to rule out thyroid disorders as part of the evaluation.

Managing Premenstrual Disorders

Treatment for premenstrual disorders should be offered when symptoms lead to reduced quality of life or interfere with daily routines. Mild cases can be managed by nonpharmacologic lifestyle modification (regular exercise, complex-carbohydrate diet, avoidance of stimulants); cognitive-behavioral therapy; selective serotonin reuptake inhibitors (SSRIs); hormonal treatment (24-day drospirenone-containing contraceptive pill use); gonadotropin-releasing hormone (GnRH) agonist, nonhormonal products (vitamin B6, chasteberry, St John's wort, ginkgo biloba); and, as a definitive therapy, hysterectomy with bilateral oophorectomy.

Moderate or severe cases often require additional medical therapy. Contraceptive pills containing drospirenone used in an extended regimen (24 instead of 21 days), and therefore limiting the hormone-free interval, have been shown to be effective.[3] There is strong evidence in support of luteal-phase or continuous use of low-dose SSRIs.[4] They target the central mechanisms and improve affective symptoms. Medical ablation of hormone synthesis by depot GnRH agonist also offers symptom relief. Add-back therapy may be required to manage hypoestrogenic side effects. If GnRH agonist therapy improves the symptoms, then a definitive solution involving hysterectomy and salpingo-oophorectomy may be considered for those who have completed childbearing and are reasonably close to natural menopause.

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