It has long been known that the menstrual cycle affects a woman's mood and well-being. For most women of childbearing age, this manifests as mild symptoms that do not require any treatment. However, for 3%–5% of women, hormonal changes during the menstrual cycle can lead to a disabling mental symptom: premenstrual dysphoric disorder (PMDD).
PMDD is a severe, disabling premenstrual syndrome. It recurs monthly during the luteal phase of the menstrual cycle, affecting women from their teens until menopause, impacting almost the most crucial period of their lives. However, women with hypothalamic amenorrhea or those who are pregnant or breastfeeding are not affected. Women with PMDD have a higher suicide risk; the rate of suicidal thoughts is 2.8 times higher, the rate of a history of suicide planning is 4.15 times higher, and the rate of suicide attempts is 3.3 times higher, necessitating urgent attention and treatment.
What are the common symptoms of PMDD? Generally, they can be divided into several categories:
Psychological symptoms include: irritability, tension, anger, insomnia, difficulty concentrating, depression, forgetfulness, severe fatigue, paranoia, anxiety, confusion, delusions, sensitivity, and frustration.
Fluid retention: swelling of the hands, feet and ankles; regular weight gain; decreased urine output; breast swelling and pain;
Respiratory system: prone to infection and allergies;
Eyes: visual changes, eye infections;
Gastrointestinal symptoms: abdominal cramps, constipation, nausea, vomiting;
Skin: Acne, itchy and inflamed skin, worsening of other skin conditions (including cold sores);
Nerve and blood vessels: headache, dizziness, numbness and tingling in the arms and/or legs, easy bruising, muscle spasms;
Other symptoms include menstrual cramps, decreased libido, changes in appetite, and hot flashes.
The most widely accepted causes of PMDD are likely increased sensitivity to fluctuations in certain hormone levels, environmental stress, and genetic predisposition. Sex steroids—estrogen and progesterone—have neuroactive properties. In rat models, they have been observed to participate in the serotonin (5-hydroxytryptamine) pathway. Serotonin, along with estrogen, is involved in mood regulation in humans.
In 2017, researchers at the National Institutes of Health (NIH) discovered that genetic changes in PMDD patients cause their cells to overreact to estrogen and progesterone, and speculated that this is involved in causing PMDD symptoms.
Some studies suggest that women with PMDD have a higher risk of developing postpartum depression during pregnancy, but other evidence contradicts this view. Regardless, as a disorder listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM), depression is extremely harmful to female patients and requires treatment once it occurs.
Existing treatment options include lifestyle modifications and medication. Regarding lifestyle changes, the following is recommended:
Change your eating habits, increase protein intake and reduce your intake of sugar, salt, caffeine and alcohol;
Regular exercise;
Stress management;
Supplement with vitamins and minerals (such as vitamin B6, calcium, and magnesium).
Sometimes medication can help control symptoms:
Antidepressants. These are generally selective serotonin reuptake inhibitors (SSRIs). SSRIs alter serotonin levels in the brain. Examples include fluoxetine, sertraline, and paroxetine hydrochloride.
Contraceptive pills. Oral contraceptive pills containing drospirenone and ethinylestradiol can be used to treat PMDD.
Over-the-counter pain relievers may help relieve physical symptoms such as cramps, joint pain, headaches, backaches, and breast tenderness. These include ibuprofen and aspirin.
Recently, scientists discovered that the use of selective progesterone receptor modulators to treat PMDD can significantly improve patients' mental symptoms, providing a promising treatment option for PMDD.
Researchers from Uppsala University, Karolinska Institute, and Umeå University in Sweden conducted a multicenter, double-blind, randomized, parallel-group clinical trial. Over three 28-day treatment cycles, 95 women with PMDD (N=1) received either 5 mg/day of the selective progesterone receptor modulator ulipristal acetate (UPA) or placebo. The total score changes from baseline to the end of treatment were recorded using the Problem Severity Scale (DRSP) before menstruation.
The results showed that the mean improvement rate of DRSP score in the UPA group was 41% (SD=18), while it was 22% (SD=27) in the placebo group. The UPA group also showed therapeutic effects on depressive symptoms, but no effect on somatic symptoms.
This means that UPA may be an effective treatment for PMDD, especially for the psychological symptoms associated with the disease. Professor Inger Sundström-Poromaa of Uppsala University points out: "These drugs have very mild side effects and are expected to become a treatment option for PMDD patients."
Looking ahead, researchers are currently investigating how progesterone receptor modulators affect the brains of women with PMDD.
Currently, the first-line treatment for PMDD is SSRIs. While these drugs are very effective, they are not suitable for all women. It is hoped that scientists will develop more potential treatments that can specifically address PMDD, thus resolving this women-specific disease.
