1. Premenstrual Syndrome and Premenstrual Dysphoric Disorder UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series

2. Objectives for PMS and PMDD  Identify the criteria for making the diagnosis of Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD)  List treatment options for PMS and PMDD

3. PMS is a group of physical, mood-related, and behavioral changes that occur in a regular, cyclic relationship to the luteal phase of the menstrual cycle and interfere with some aspect of the patient’s life PMDD identifies women with PMS who have more severe emotional symptoms (such as anger, irritability, and depression) that may require more extensive therapy Definition

4.  PMS symptoms - 75%- 85% of women  Severe/debilitating PMS - 5-10% of women  PMDD - 3-5% of women Incidence

5. Severe (PMDD) Moderate (PMS) Mild (PMS) None Spectrum of Premenstrual Syndromes Premenstrual Syndrome Severity Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 36 (387).

6. Somatic Symptoms  Breast tenderness  Abdominal bloating – most common, occurs in 90%  Headache  Swelling of extremities  Weight gain PMS/PMDD: Symptoms

7. Affective Symptoms  Depression  Angry outbursts  Irritability  Anxiety  Confusion  Social withdrawal  Decreased concentration  Sleep disturbance  Appetite change/food cravings PMS/PMDD: Symptoms

8. Sample: Daily Symptoms Calendar Diagnostic tool used to assist the patient with recording her premenstrual symptoms diary Endicott and Harrison 2006. 5.Endicott, J., & Harrison, W. Daily Record of Severity of Problems Calendar.

9.  Patient reports 1 affective symptom and somatic symptom(s) during the luteal phase before menses  Symptoms relieved within 4 days of onset of menses, without recurrence until at least cycle day 13  Symptoms occur in 2 consecutive menstrual cycles  Patient suffers from identifiable dysfunction in social or economic performance PMS: Diagnosis

10. DSM-IV Criteria  Symptoms interfere with usual functioning and relationships  Symptoms are not an exacerbation of another disorder  Symptoms resolve at onset of menses  Premenstrual timing is confirmed by menstrual calendar in 2 consecutive cycles PMDD: Diagnosis

11. DSM-IV Criteria  At least 5 of 11 premenstrual symptoms  At least 1 of the following:  Depressed mood  Marked anxiety  Marked affective lability  Marked irritability  Other possible symptoms  Decreased interest in regular activities  Difficulty concentrating  Lethargy/fatigue  Appetite change/food cravings  Sleep disturbance  Feelings of being overwhelmed  Physical symptoms (bloating, weight gain, breast tenderness, edema) PMDD: Diagnosis

12. Rule out other diseases:  Psychological disorders  Depression, Bipolar disorders, Personality disorders, Anxiety  Gynecologic disorders  Dysmenorrhea, Endometriosis, Pelvic Inflammatory Disease, Perimenopause  Endocrine disorders  Thyroid disease, Adrenal disorders, True hypoglycemia  GI conditions  Inflammatory bowel disease, Irritable bowel syndrome  Drug or substance abuse  Chronic fatigue states PMS/PMDD: Differential Diagnosis

13.  Supportive therapy  Lifestyle changes  Frequent exercise  Nutritional supplements  Magnesium sulfate 360 mg/d  Calcium 1200 mg/d  Vitamin E 400 IU/d  Vitamin B 6 100 mg/d PMS/PMDD: Treatment (Conservative)

14.  NSAIDs  Anti-depressants  SSRI’s (Fluoxetine or Sertraline)  Buspirone  Spironolactone - bloating  Bromocriptine or Danocrine – mastalgia  Ovulation suppression  GnRH agonists (e.g. Lupron)  Danazol  OCPs PMS: Treatment (Medical)

15.  SSRIs  Can be taken throughout the cycle or during the luteal phase of the cycle  Fluoxetine 20-60 mg qd  Sertraline 50-150 mg qd PMDD: Treatment (Medical)

16.  Oophorectomy  Not generally recommended  Irreversible  Reserved for severely affected patients who only respond to GnRH agonists PMS/PMDD: Treatment (Surgical)

17. Bottom Line Concepts  PMDD identifies women with PMS who have more severe emotional symptoms that may require intensive therapy.  The physiologic mechanism that results in the occurrence of PMS and PMDD is not well understood.  The diagnosis of PMS and PMDD is based on documentation of the relationship of the patient’s symptoms to the luteal phase.  DSM-IV criteria are used to establish the diagnosis of PMDD.  In addition to lifestyle changes, behavioral therapies, and dietary supplementation, some pharmacologic agents have been shown to have symptom relief.  As an overall clinical approach, treatments should be employed in increasing orders of complexity.

18. References and Resources  APGO Medical Student Educational Objectives, 9 th edition, (2009), Educational Topic 49 (p104-105).  Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 39 (p347-352).  Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 36 (p386-388).

19. Dysmenorrhea UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series

20. Objectives for Dysmenorrhea  Define dysmenorrhea and distinguish primary and secondary dysmenorrhea  Describe the pathophysiology and identify the etiologies of dysmenorrhea  Discuss the steps in the evaluation and management options for dysmenorrhea

21. Painful menstruation that prevents a woman from performing normal activities  Primary dysmenorrhea – no readily identifiable cause  Secondary dysmenorrhea – identifiable organic cause Definition

22.  Caused by excess prostoglandin F 2α (PGF 2α ) and PGE 2 produced from shedding endometrium  Prostoglandins are potent smooth-muscle stimulants that cause uterine contractions and ischemia  Prostoglandin F 2α causes contractions in smooth muscle elsewhere in the body, resulting in nausea, vomiting, and diarrhea Primary Dysmenorrhea: Pathophysiology

23.  Pain  Onset within 2 years of menarche  Begins a few hours before or just after onset of menses  Lasts 48 – 72 hours  Described as “cramp-like”  Strongest over lower-abdomen  Radiates to back or inner thighs  Associated symptoms  Nausea and vomiting  Fatigue  Diarrhea  Lower backache  Headache Primary Dysmenorrhea: Symptoms

24.  Reassurance and explanation  Medical  NSAIDs  Hormonal contraceptives (e.g. OCPs, IUD, Vaginal rings, Patches)  Progestins (e.g. Medroxyprogesterone acetate)  Tocolytics (e.g. Salbutamol)  Analgesics  Other Measures  Transcutaneous nerve stimulation  Acupuncture  Psychotherapy  Hypnotherapy Primary Dysmenorrhea: Treatment

25.  Depends on underlying (secondary) cause and in most cases is not well understood  Causes of secondary dysmenorrhea:  Endometriosis  Pelvic inflammation  Adenomyosis  Fibroid tumors (benign, malignant)  Ovarian cysts (e.g. endometriosis, luteal cysts)  Pelvic congestion Secondary Dysmenorrhea: Pathophysiology

26.  Pain  Develops in older women (30’s to 40’s)  Not limited to menses  Associated symptoms  Dyspareunia  Infertility  Abnormal uterine bleeding Secondary Dysmenorrhea: Symptoms

27. ConditionSigns and Symptoms EndometriosisPain extends to premenstrual and postmenstrual phase Deep dyspareunia Tender pelvic nodules (e.g. uterosacral ligaments) Onset in 20’s – 30’s Pelvic inflammationPain initially menstrual, with each cycle extends into premenstrual phase Intermenstrual bleeding Pelvic tenderness Fever, chills, malaise Adenomyosis,Pain + menorrhagia Uterus symmetrically enlarged, mildly tender, “boggy” Uterine fibroidsPain + menorrhagia Firm, irregularly enlarged uterus Ovarian cystsMid-cycle, unilateral pain Pelvic congestionDull, ill-defined pelvic ache Pain worse premenstrually and relieved by menses History of sexual problems

28.  Management consists of treatment of the underlying disease  Treatment used for primary dysmenorrhea often helpful Secondary Dysmenorrhea: Treatment

29. Bottom Line Concepts  Primary and secondary dysmenorrhea are a source of recurrent disability for a significant number of women in their early reproductive years.  Primary dysmenorrhea is caused by excess prostoglandin produced by the shedding endometrium.  Secondary dysmenorrhea is due to organic pelvic disease, including; endometriosis, PID, adenomyosis, uterine fibroids, and pelvic congestion.  Primary dysmenorrhea presents within 2 years of menarche, where as secondary dysmenorrhea more often presents in older women.  For patient’s with dysmenorrhea, the physical exam is directed at uncovering possible causes of secondary dysmenorrhea.  Treatment of secondary dysmenorrhea should be directed at the underlying condition.

30. References and Resources  APGO Medical Student Educational Objectives, 9 th edition, (2009), Educational Topic 46 (p98-99).  Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 30 (p277-279).  Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 21 (p256-259).