PANCE Blueprint Psychiatry (6%)

Premenstrual dysphoric disorder (PMDD)

Patient will present as → a 26-year-old patient is complaining of depression and anxiety just prior to her menses. The symptoms have been going on for more than 1 year, but are now starting to interfere with her relationships and her productivity at work. One week prior to menses each month she experiences a depressed mood, a feeling of being on edge, increased irritability, difficulty sleeping, a feeling of being overwhelmed, and is easily fatigued. She charted her symptoms daily in a log and returned to the office two cycles later. The log is consistent with the history. Her physical examination and general laboratory profile showed no abnormalities.

During what phase of the menstrual cycle do symptoms of PMDD manifest?
Symptoms occur during the luteal phase of the menstrual cycle and resolve with menstruation.

Key Points:

  • Repeated episodes of significant depression and related symptoms during the week before menstruation

DSM-5 Diagnostic Criteria

In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week post menses.

One (or more) of the following symptoms must be present:

  • Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).
  • Marked irritability or anger or increased interpersonal conflicts.
  • Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.
  • Marked anxiety, tension, and/or feelings of being keyed up or on edge.

One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from above.

  • Decreased interest in usual activities (e.g., work, school, friends, hobbies).
  • Subjective difficulty in concentration.
  • Lethargy, easy fatigability, or marked lack of energy.
  • Marked change in appetite; overeating; or specific food cravings.
  • Hypersomnia or insomnia.
  • A sense of being overwhelmed or out of control.
  • Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating,” or weight gain.

The symptoms are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).

SSRIs (fluoxetine 10 mg, sertraline 50 mg qd, etc) are useful for the treatment of PMDD.

  • These medications can be administered continuously during the menstrual cycle or only when the patients experience symptoms.
  • Luteal phase or intermittent administration involves initiating medication at the time of ovulation and stopping it at the beginning of menses.
  • SNRIs such as venlafaxine may also be effective in women with predominantly psychological symptoms.

Other useful agents are benzodiazepines (addictive) and the tricyclic antidepressant clomipramine (25 mg QD as starting dose).

Birth control, low-dose estrogen, and diuretics may also be beneficial.

Gonadotropin-releasing hormone (GnRH) - accelerated bone loss and vasomotor symptoms associated with long-term use of a GnRH agonist will require add-back therapy.

  • Hormonal intervention with monthly intramuscular injections of leuprolide has been reported effective in some patients; however, it should be reserved only for patients unresponsive to first- and second-line agents.

Nutritional supplementation (vitamin B6 up to 100 mg/day, vitamin E up to 600 IU/day, calcium carbonate up to 1200 mg/day, and magnesium up to 500 mg/day) are also commonly used for symptom reduction in some patients with limited results.

Ovariectomy may be considered in severe refractory cases.

Picmonic (Phases of the menstrual cycle and PMDD)

The 28-day menstrual cycle can be described by the ovulatory hormones in two phases: the follicular (proliferative) phase and the luteal (secretory) phase. The follicular phase describes the balance between FSH, estrogen, LH, and ovulation. In PMDD symptoms occur during the luteal phase of the menstrual cycle and resolve with menstruation.

Ovulatory Hormones II – Luteal Phase
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Ovulatory Hormones I – Follicular Phase
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Question 1
Which of the following factors is most strongly associated with the pathophysiology of Premenstrual Dysphoric Disorder (PMDD)?
A
Elevated levels of estrogen during the luteal phase
Hint:
While hormonal fluctuations are involved in PMDD, it is the sensitivity to these changes, rather than the absolute levels of estrogen, that is more critical in the pathophysiology of PMDD.
B
Increased production of progesterone metabolites
Hint:
Similar to estrogen, it's the sensitivity to progesterone changes rather than increased production of its metabolites that is associated with PMDD.
C
Deficiency of vitamin D and calcium
Hint:
While these deficiencies can affect mood and physical symptoms, they are not directly associated with the pathophysiology of PMDD.
D
Chronic endometrial inflammation
Hint:
This is not a recognized factor in the pathophysiology of PMDD.
E
Abnormal serotonin neurotransmission
Question 1 Explanation: 
Explanation: PMDD is thought to be primarily related to abnormal serotonin neurotransmission. Women with PMDD appear to have an abnormal response to normal hormonal fluctuations, particularly a heightened sensitivity to the normal cyclical changes in estrogen and progesterone, which in turn affects serotonin levels. This neurotransmitter is key in regulating mood, and its dysregulation is linked to the mood and anxiety symptoms characteristic of PMDD.
Question 2
A 27-year-old woman is presenting to her physician assistant with a constellation of physical and affective symptoms that she believes are associated with her menstrual cycle. Which of the following is consistent with premenstrual syndrome and does not warrant further testing?
A
Difficulty swallowing
Hint:
These symptoms are not consistent with PMS.
B
Sudden bleeding
Hint:
These symptoms are not consistent with PMS.
C
Weight gain
D
Breast size decrease
Hint:
These symptoms are not consistent with PMS.
E
Cold intolerance
Hint:
These symptoms are not consistent with PMS.
Question 2 Explanation: 
Premenstrual syndrome (PMS) encompasses a range of both physical and emotional symptoms that occur during the luteal phase of a woman's menstrual cycle, typically easing off once menstruation begins or shortly after. To diagnose PMS, a thorough history is taken to distinguish it from other conditions that might have similar symptoms, such as anemia, hormonal imbalances, or various psychiatric disorders. Common symptoms of PMS include mood swings like depression and anxiety, a lack of pleasure or interest in activities (anhedonia), tiredness, headaches, bloating, and weight gain. These symptoms are significant enough to disrupt daily activities in social or work environments. Notably, there's a symptom-free period of at least one week during each menstrual cycle.
Question 3
A 35-year-old woman diagnosed with PMDD has not responded to lifestyle modifications and cognitive-behavioral therapy. She is seeking pharmacological treatment. Which of the following is the most appropriate first-line pharmacological treatment for her condition?
A
Clomiphene citrate
Hint:
This is used in the treatment of infertility, not PMDD.
B
Gonadotropin-releasing hormone (GnRH) agonists
Hint:
These are used in severe cases of PMDD where other treatments have failed, due to their significant side effects and risk of inducing menopause-like symptoms.
C
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Hint:
While they can help with physical symptoms like cramps, they do not address the core emotional and psychological symptoms of PMDD.
D
Selective serotonin reuptake inhibitors (SSRIs)
E
Combined oral contraceptives
Hint:
OCP may be beneficial in some cases, but they are not considered the first-line pharmacological treatment for PMDD.
Question 3 Explanation: 
Explanation: SSRIs are considered the first-line pharmacological treatment for PMDD. They have been shown to be effective in reducing the emotional and physical symptoms of PMDD. SSRIs can be used continuously or just in the luteal phase of the menstrual cycle. Their efficacy in PMDD is thought to be related to their ability to modulate serotonin neurotransmission, which is implicated in the pathophysiology of PMDD.
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References: Merck Manual · UpToDate

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