​Kembara Xtra - Medicine - Premenstrual Syndrome and Premenstrual Dysphoric Disorder

​Kembara Xtra - Medicine - Premenstrual Syndrome and Premenstrual Dysphoric Disorder  
The luteal phase of menstruation is when premenstrual syndrome (PMS), a mix of physical and mental symptoms severe enough to interfere with daily life, cyclically occurs.
According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS) characterized by severe recurrent depressive and anxiety symptoms that begin during the luteal phase and subside a few days before the onset of menstruation.
 Endocrine/metabolic, neurological, and reproductive system(s) affected 

Prevalence of Epidemiology
Before menstruation, many women have physical and psychological symptoms that range from minor molimina to severe and incapacitating ones.
It has been estimated that 20% to 30% of menstrual women suffer with PMS. According to DSM-5 criteria, 1.2% to 6.4% of women experience PMDD, with up to 18% of menstrual women partially matching the criteria.


Pathophysiology and Etiology 

Although the pathophysiology is still not fully known, there are two basic schools of thought:  Allopregnanolone, a progesterone metabolite that fluctuates in concentration, interacts with serotonin and gamma-aminobutyric acid (GABA) receptors, resulting in decreased GABA-mediated inhibition and decreased serotonin levels as a result.
The fundamental issue is a diminished function of the serotonin system, specifically the serotonin transporter, which when affected by sex hormones results in decreased serotonin levels in those with PMS/PMDD.

The significance of genetic predisposition is debatable, but twin studies certainly indicate a genetic component.
The serotonergic 5HT1A receptor gene and allelic forms of the estrogen receptor gene (ESR1) may both be involved.

Risk Elements 
Age: typically appears in the late 20s to mid 30s; Mood disorder history (including major depression, bipolar disorder), anxiety disorder, personality disorder, or substance abuse; Family history; Low parity; Cigarette smoking and other nicotine-containing products; Psychosocial stressors/history of trauma; High BMI (>27.5)

Accompanying Conditions 
In patients with PMS/PMDD, comorbid mood disorders and/or anxiety disorders are very common.

The International Society for Premenstrual Disorders (ISPMD) has defined criteria for the diagnosis of PMS, which include: - Physical or emotional symptoms
- Symptoms appear during the luteal phase and diminish when menstruation starts - A week without symptoms
- Symptoms during the luteal phase are linked to substantial impairment. The DSM-5 includes PMDD diagnostic criteria that were developed by the American Psychiatric Association in 2013.
In the week following menses, symptoms are limited or nonexistent (during the majority of menstrual cycles over the past year), improving in the first few days after menses start.
5 of the following, 1 of which must be one of the first 4: - Prominently low mood, a sense of helplessness, or self-deprecating thoughts - Prominently nervous, tense, or feeling on edge - Prominent affective lability (mood swings)
- A substantial increase in interpersonal disputes or impatience. Lethargy, easy fatigue, lack of energy, changes in appetite, overeating, and food cravings. Hypersomnia or insomnia. Feeling out of control or overwhelmed. Subjective difficulty concentrating. Physical symptoms like abdominal bloating, breast tenderness, headaches, weight gain, and joint/muscle pain.  Emotional symptoms may be overlaid on an underlying psychiatric problem but may not constitute a worsening of another condition, such as panic disorder/major depression. Symptoms must be severe enough to interfere with job, school, regular social activities, or relationships with others.
 The prospective patient's record of symptoms for at least two consecutive menstrual cycles must confirm the criteria; otherwise, the diagnosis should include the word "provisional."
Symptoms shouldn't be linked to drug misuse, prescription drugs, or other illnesses.
A validated tool, such as the Daily Record of Severity of Problems (available online at http://www.aafp.org/ afp/ 2011/ 1015/ p918-fig1.pdf) or a comparable inventory, can be used to make the diagnosis.

clinical assessment 

No particular physical examination is necessary; if further patient symptoms warrant it, thyroid and pelvic exams may be taken into account. 

Differential diagnosis: Bipolar disorder, major depression, anxiety, thyroid disorders, perimenopause, premenstrual migraine, chronic fatigue syndrome, irritable bowel syndrome (painful symptoms), seizures, anemia, endometriosis (painful symptoms), drug or alcohol abuse.

Laboratory Results If a traditional history is given, lab tests are not necessary due to the recurrent nature of symptoms.
Hemoglobin may be used to rule out anemia.
- TSH (thyroid-stimulating hormone) serum levels to rule out hypothyroidism To identify the causes of dysmenorrhea and pelvic discomfort, imaging with pelvic ultrasonography may be required.

Management 
Although physical activity boosts beta-endorphins in the brain, it is yet unknown how it might be used to treat premenstrual illnesses.


First Line of Medicine
When compared to placebo, SSRIs are advised as the first-line therapy for the management of somatic, functional, and behavioral symptoms of PMS and PMDD:
All SSRIs studied proved to be effective; there is no discernible difference in effectiveness between continuous full-cycle dose and intermittent luteal phase dosing.
SSRIs are effective at low dosages, but in some people, titrating the dose may be necessary to achieve the desired response.
Although the effects of higher doses are greater, so are the adverse effects.
Fluoxetine (Prozac, Sarafem) 20 mg daily or 20 mg daily only during the luteal phase; Sertraline (Zoloft) 50 to 150 mg daily or 50 to 150 mg daily only during the luteal phase; Citalopram (Celexa) 10 to 30 mg daily or 10 to 30 mg daily only during the luteal phase; Adverse effects (number needed to harm [NNH] with moderate-dose SSRI]: nausea (N
Patients on monoamine oxidase inhibitors (MAOIs) are contraindicated. Precautions - It's not known whether people using SSRIs for PMDD are at increased risk of suicidal thoughts and actions in children and adolescents with depressive disorders.
Bipolar disorder, epilepsy, and QTc prolongation (when citalopram is used)
- Dysfunctions of the liver and kidneys
Next Line
If SSRIs are ineffective, one should investigate alternative therapies: Spironolactone (Aldactone), 50–100 mg/day for 7–10 days during the luteal phase; beneficial for fluid retention.
Lethargy, headaches, irregular periods, hyperkalemia, and other negative effects - Consistent electrolyte monitoring is advised due to the possibility of hyperkalemia.
 Oral contraceptive pills (OCPs) - OCPs can have side effects that are comparable to those of PMDD.
- A shorter placebo interval (e.g., 24 active pills with 4 placebo days [24/4] compared with 21/7 preparations) or an extended cycle of OCP use (e.g., 12 weeks on and 1 week off) may be advantageous.
- OCPs containing the progestin drospirenone, which is chemically related to spironolactone, may lessen PMDD-related physical symptoms and mood swings. Attention: Compared to other OCPs, there may be a little increase in the risk of venous thromboembolism.
Levonorgestrel/ethinyl estradiol therapy given continuously may lessen PMDD patients' symptoms.
 Proposed formulations for OCP:
Levonorgestrel 90 g/ethinyl estradiol 20 g (Amethyst/Lybrel): 1 tablet/day Anxiolytics - Alprazolam (Xanax) 0.25 mg TID-QID only during luteal phase; taper at the onset of menses (other benzodiazepines not studied for PMDD); caution: Ovulation inhibitors - Buspirone (BuSpar) 10 to 30 mg/day divided BID-TID in the luteal phase - Leuprolide (Lupron) depot 3.75 mg/month IM - Gonadotropin-releasing hormone (GnRH) agonists
 Safety measures: Menopause-like side symptoms, such as vaginal dryness, irritability, headaches, hot flashes, and osteoporosis Danazol (Danocrine) 300 to 400 mg BID; adverse effects: androgenic and antiestrogenic effects (e.g., amenorrhea, weight gain, acne, fluid retention, hirsutism, hot flashes, vaginal dryness, emotional lability) - Estrogen, transdermal preferred, 100 to 200 g: limit treatment to 6 months; may be the first step if considering bilateral oophorectomy for severe  Requires concurrent progesterone add-back therapy to protect against uterine hyperplasia and endometrial cancer Precautions: increased risk of blood clots, stroke, heart attack, and breast cancer Progesterone: inadequate evidence to sustain usage


Referral 
If the patient has a sufficient response to treatment, short-term follow-up (within 1-3 months) can determine this. If not, a psychiatrist should be consulted for additional assessment.


Further Therapies 
Given its use for symptom reduction in other mood disorders, cognitive-behavioral treatment (CBT) is potentially beneficial for PMS/PMDD, but there is a lack of concrete evidence to support this.

Surgical Techniques S
For rare, recalcitrant instances with severe, incapacitating symptoms, bilateral oophorectomy—typically combined with hysterectomy—is a possibility.

Alternative Therapies 

With no indication of harm, acupuncture outperformed progestins, anxiolytics, and sham acupuncture.
● According to certain data, the following should be used: - 600 mg BID of calcium
- 50 to 100 mg each day of vitamin B6
- Chasteberry (Vitex agnus-castus): 20 to 40 mg/day of fruit extract, or 4 mg/day of an extract containing 6% agnuside. Omega-3 fatty acids: 2 grams per day; inadequate information exists for the following: - Manganese: 1.8 mg/day - St. John's wort: 900 mg/day - Magnesium: 200 to 400 mg/day - Vitamin D: 2,000 IU/day - Vitamin E: 400 IU/day
- Soy: 68 mg isoflavones per day
The following products/interventions have not been found to be helpful for PMS/PMDD, although not all studies are of high quality and able to completely rule out the possibility of benefit: Ginkgo: 160 to 320 mg/day Saffron: 30 mg/day There is insufficient evidence to support the efficacy and/or safety of herbal products. Evening primrose oil, black currant oil, black cohosh, wild yam root, dong quai, kava kava, and light-based therapy are all effective treatments.

Patient Follow-Up Monitoring
When SSRIs are first started, there is an increased risk of suicide thoughts and actions among kids and teenagers with depressive disorders; it is unclear if this risk also applies to people taking SSRIs for PMDD.

Diet 
Consume less alcohol, coffee, dairy products, salt, sugar, and other additives (anecdotal reports).
Eat complex carbohydrate-rich foods in small, regular servings (limited data).

Patient education – Encourage patients to follow a balanced diet reduced in saturated fat and caffeine, high in calcium, vitamin D, and omega-3 fatty acids.
 Encourage patients to stop using cigarettes and other nicotine products (further study is required to determine the advantages of quitting smoking in PMS and PMDD).
Women should be assured that they are not "crazy." Despite being poorly understood, PMDD is a real condition with a physiologic foundation that is frequently treatable.


Prognosis: The symptoms of many patients can be successfully managed. Menopause causes PMS to stop, although if the ovaries are still present after a hysterectomy, PMS may still persist.