Premenstrual Dysphoric Disorder: Epidemiology, Etiology

Epidemiology

Irritability has been identified as the most common premenstrual symptom in USA and European samples. Studies examining age, menstrual cycle characteristics, cognitive attributions, socioeco-nomic variables, lifestyle variables and number of children have not yielded consistent conclusions. Studies have suggested some genetic liability for PMS, but the overlap with genetic liability for major depression or personality characteristics has received mixed. A polymorphism in the serotonin transporter promoter gene has been suggested in women who have both PMDD and seasonal affective disorder (Praschak-Rieder et al., 2002). Ele-vated lifetime prevalence of major depressive disorder in women with PMDD has been reported in several studies as well as an elevated lifetime prevalence of postpartum. Even though pre-menstrual symptoms are described in women from menarche to menopause, it is unclear if symptoms remain stable or increase in severity with age. PMS has been described in several countries and cultures and some have a preponderance of somatic rather than emotional symptoms.

Etiology

Since abnormalities in the hypothalamic-pituitary-gonadal axis (HPG) have not been identified, it is thought that premenstrual symptoms may occur due to a differential sensitivity to mood-perturbing effects of gonadal steroid fluctuations in women with PMS and PMDD. It is probable that the etiology of the “differen-tial sensitivity” is multifactorial. The specific neurotransmitter, neuroendocrine and neurosteroid abnormalities in women with PMS and PMDD are not known, but serotonin, norepinephrine, gamma-aminobutyric acid (GABA), allopregnanolone (an anxi-olytic metabolite of progesterone that acts at the GABA_A recep-tor) and factors involved in calcium homeostasis are all possibly involved.

A large number of studies have reported abnormalities in the serotonin system in women with PMS and PMDD. Several studies have also suggested that women with PMDD have de-creased luteal phase levels of GABA, abnormal allopregnanolone levels, and decreased sensitivity of the GABA_A receptor as shown by flumazenil challenge, and the sedative and saccadic eye veloc-ity responses to benzodiazepines. It is possible that the rapid effi-cacy of selective serotonin reuptake inhibitors (SSRIs) in PMDD may be due in part to their ability to increase allopregnanolone levels in the brain, thus enhancing GABA transmission as well as serotonin transmission.

Several factors that influence calcium and bone homeostasis fluctuate with the menstrual cycle and it is possible that some of these factors are abnormal in women with PMS and PMDD Thys-Jacobs and colleagues (1995) reported that women with PMS had reduced periovulatory calcium levels and elevated parathyroid hormone levels compared with controls, perhaps secondary to elevated preovulatory estrogen levels, and these authors proposed that women with PMS may have a cyclical, transient secondary hyperparathyroidism. It has been reported that when calcium homeostasis is corrected in primary hyperparathyroidism, cerebrospinal fluid monoamine metabolites normalize and affective symptoms are reduced. It is possible that the administration of supplemental calcium normalizes the peri-ovulatory fluctuations in calcium and parathyroid hormone, thus regulating calcium effects on neurotransmitter synthesis and release leading to symptom relief in women with PMS.