Premenstrual dysphoric syndrome or premenstrual dysphoric disorder (PMDD) is a more severe variant of the premenstrual syndrome (PMS), showing intense mood change as the most perturbing and debilitating factor within the set of symptoms and affects 3–8% of menstruating women. PMS and PMDD do not occur in women who are pregnant, who do not have ovaries, or who have the menopause. 

Its etiology has not been well defined because it is influenced by hormonal, family, environmental, and sociocultural factors; therefore, it does not necessarily have physical symptoms. Such condition, however, has a significant influence on the daily and working activities of women.

Wide variety of luteal phase (second half of period) symptoms that are bothersome and usually disappear or greatly improve shortly after the onset of bleeding. Symptoms of PMDD can occur from the menarche (the onset of periods) to the menopause and are present in women's life throughout the whole reproductive period, often being interpreted as symptoms of an imaginary disorder and being caused by the increasingly stressful modern life. On the other hand, countless women have reported an increase in the severity and duration of the symptoms as they get closer to the menopausal period, which brings consequences to their quality of life.

The differential diagnosis between the premenstrual syndrome (PMS) and PMDD is difficult to be established because there is not any laboratory test that can serve as a biological marker of one or the other syndrome. However, most gynecologists or psychiatrists establish their diagnosis based on the assessment of the exacerbated symptoms during the menstrual period (see below), considering both physical and depressive symptoms. The PMDD diagnosis is also based on the assumption that the condition with the premenstrual symptoms is mainly psychiatric and should be separated from a condition with merely somatic complaints. Physical complaints are not mandatory symptoms to meet the criteria for PMDD.

Different subtypes of PMDD have been described, and selecting the appropriate treatment for the subtype is an important consideration for management. A large number of clinical studies demonstrate that fluoxetine, the first-line treatment for PMDD, can address some of the symptoms of PMDD, including dysphoria, food cravings, tension, and anxiety, but it has no effect on other clinical manifestations, such as sexual hypoactivity, indicating that PMDD has subtypes that differ in their pathogenesis.

Symptoms

The main characteristic of PMDD is the clinical recurrence during the luteal phase and mood and behavioral symptoms, among which depression, anxiety, affective lability, tension, irritability, and sleep disorder are the most frequent ones. In addition, it causes severe impairment of the individual's social and occupational functioning, which usually gets worse closer to the menstrual flow phase and generally ceases immediately after the menstrual flow starts.

The severity and frequency of the symptoms seem to be quite variable, and they may vary in the same woman from month to month. As many as 80% of women experience mood and physical symptoms associated with the menstrual cycle, and epidemiological studies have shown that for 24%–32% of menstruating women, the symptoms are moderate or severe. 

Associated diseases

PMDD is diagnosed as a "depressive disorder not otherwise specified". This indicates that PMDD is equivalent to other depressive disorders in some way. Many studies have found a correlation between premenstrual symptoms and depression. For example, women with PMDD or PMS have a greater history of depression. However, it is difficult to distinguish PMDD from an exacerbation of symptoms of other psychiatric disorders because the PMDD scale is self-rating.

Complications

PMDD can significantly affect one’s work and social functioning one week before the menstrual period.

Risk factors

In particular, ovarian steroid hormones appear to play an important role in this syndrome. Women with PMS/PMDD seem to have more symptoms with normal cyclical levels of steroid hormones; however, during anovulatory cycles, these symptoms are not observed. 

Prevention

PMDD treatment is aimed at preventing or minimizing symptoms. Prevention itself does not exist. PMDD appears to be inextricably linked with fluctuating values in hormone levels and in particular with progesterone (sex hormone involved in the menstrual cycle, pregnancy and embryogenesis of humans). Therefore, one of the most common approaches to treating PMDD is to try ovulation suppression. This decision is made in conjunction with patients’ fertility and contraceptive needs. 

The various methods of doing this are: combined oral contraceptive pill (COCP), gonadotropin-releasing hormone (GnRH) analogues, and bilateral oophorectomy (surgical removal of an ovary or ovaries). Other approaches include antidepressants and the use of vitamin and mineral supplements and alternative therapies.

The condition can be so disruptive and severe that bilateral salpingo-oophorectomy (removal of the fallopian tube and ovary) is required, but the hormone replacement therapy that is then necessary can cause symptoms to resume if it contains progesterone. For this reason hysterectomy (surgical removal of uterus) is often considered as it allows for estrogen-only hormone replacement therapy. Surgery is a last resort and should only be considered after extensive counseling, and there must be a trial period with GnRH analogues before the decision is made.

Low progesterone levels early in the menstrual cycle have been linked to an increased susceptibility to PMDD. This might indicate that indeed progesterone was problematically low for conception and women could have problems with getting full term pregnancy, because progesterone a crucial part of the menstrual cycle and maintenance the uterine lining throughout pregnancy.

The early identification and the appropriate treatment of PMDD reduce the probability of chronic and recurrent symptoms. There is still a controversy regarding the methods of intervention for this disorder; however, changes in the eating habits, administration of medication (psychotropic and contraceptive drugs), and physical activity have shown positive results for women with PMDD. If women have unsuccessful full term pregnancy due low progesterone, it may be supplemented during intrauterine inseminations (IUI's) and later in vitro fertilization (IVF) cycles.

Until recently, the only treatment for women with PMDD was psychoactive drugs, such as selective serotonin reuptake inhibitors. Several years ago, there has been evidence of the beneficial role of combined hormonal contraceptives in controlling PMDD symptoms. Oral combined hormonal contraceptives that contain drospirenone in a 24+4-day regimen are the only drugs that have been approved by US Food and Drug Administration (FDA, federal agency responsible for protecting and promoting public health) for the treatment of PMDD, but there is scientific evidence that other agents, with other formulations and regimens, could also be effective for the treatment of this condition. However, it remains unclear whether the beneficial effect of combined hormonal contraceptives is associated with the type of estrogen or progestogen used or the treatment regimen.

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