TG described her symptoms as severe PMS, but I suspected that she was suffering from premenstrual dysphoric disorder (PMDD). Both PMS and PMDD are associated with disturbing, predictable, recurring, cyclic symptoms that start towards the end of the cycle and stop shortly after the onset of menstruation. Common symptoms include headaches, breast tenderness, bloating, irritability, depression, angry outbursts, and anxiety. The difference between PMDD and PMS is the severity and predominance of mental/emotional symptoms in PMDD and the marked impairment of personal/social relationships, including increased conflicts. PMDD is at the most severe and disabling end of the spectrum of premenstrual disorders.
The diagnostic criteria for PMDD are detailed below and TG experienced at least 5 of the symptoms including 3 of the specific symptoms, which seriously interfered with her social activities and personal relationships.
Diagnostic Criteria for PMDD
Presence of 5 of 11 depressive, anxiety, cognitive, or physical symptoms, with at least 1 of the first 4 specific symptoms* experienced in most of the menstrual cycles for the past year. The symptoms may begin a week before menses and must completely remit within a few days after the onset of menses.
Depressive, anxiety, cognitive, and physical symptoms:
Depressed mood, feelings of hopelessness, self-deprecation
Sudden feeling of sadness or tearfulness, with increased sensitivity to rejection
Anxiety, tension, feeling of being "keyed up" or "on edge”
Persistent irritability, anger, increased interpersonal conflicts
Decreased interest in usual activities
Lethargy, fatigue, lack of energy
Changes in appetite and cravings for certain foods
Insomnia or hypersomnia
Feeling overwhelmed or out of control
Breast tenderness or swelling
Joint or muscle pain
2. Symptoms interfere with social, occupational, sexual, or school functioning.
3. Symptoms are discretely related to menstrual cycle and are not merely worsening of preexisting depression, anxiety, or personality disorder.
4. Criteria 1, 2, and 3 must be confirmed prospectively by daily ratings for at least 2 consecutive symptomatic menstrual cycles.
The exact cause of PMDD is unknown, but it appears to be related to an abnormal response of neurotransmitters including serotonin and GABA to normal ovarian function. In PMDD there is no demonstrable hormonal imbalance, rather PMDD is the result of the way that oestrogen and progesterone affect serotonin and GABA metabolism.
PMDD usually starts within 1-2 weeks before the onset of menstruation, when progesterone is climbing and oestrogen is decreasing. Progesterone is converted to alloprogesterone which normally interacts with GABA receptors in the brain to produce feelings of calmness and relaxation. In PMDD however, it is thought that the GABA receptor is malformed which means that the alloprogesterone does not lead to calmness, and instead results in high anxiety, anger and other mental/emotional symptoms. This is probably why TG had such an extreme reaction to the synthetic progesterone she received during IVF treatment - the very high level of progesterone induced extreme PMS symptoms. The malformation of the GABA receptor is associated with various nutritional deficiencies, including vitamin K, magnesium and vitamin B6.
At the same time, the decreasing oestrogen level in the luteal phase is associated with a decrease in the level of serotonin. In PMDD this can be hightened, leading to a serotonin imbalance which can cause depression, anxiety, sugar cravings, insomnia, headaches, obsessions and compulsions.
Serotonin is not found in food, but it is synthesised from l-tryptophan, which is found in protein as an amino acid. Synthesis of serotonin requires vitamin B6 and vitamin D. TG had vitamin D deficiency as evidenced by her blood test, which likely contributed to her ‘winter blues’ and may have impacted her serotonin level and led to insomnia. Melatonin, the sleep hormone, is synthesised from serotonin, and hence sleep is worsened when vitamin D is low.
TG’s diet, which was high in sugars and starch, and low in vegetables, fibre, omega 3 fats and water was also a likely contributor to her symptoms. A high carbohydrate intake depletes the body of essential vitamins and minerals, while a lack of omega 3 fats and vegetables can lead to deficiencies in essential anti-oxidants and micronutrients.