Perimenopause and Menopause

1. Perimenopause and Menopause Gemma, Rebecca, Alyssa

3. CASE A 50 yo woman complains of irregular menses over the past year. It has now been 6 months since her last cycle. She describes mood changes, feelings of inadequacy, vaginal dryness, difficulty sleeping with episodes of warmth and sweating that awaken her. On examination, her blood pressure is 120/68, heart rate is 90 bpm, and temperature 37.6 degree Celcius. Cardiac and lung examination are unremarkable. Breast examination is normal. Examination of external genitalia is normal.

4. Objectives • Describe and recognize the following regarding menopause: • ageof presentation, physiologic changes, signs and symptoms andinvestigations. • Describe and recognize the following regarding menopause: • Non-pharmacologic and pharmacologic management, including effects on other organ systems. • List common signs and symptoms of menopause.

5. Perimenopause • Transition between normal ovulatory cycles to cessation of menses, and the first year of amenorrhea • Begins when the length of the menstrual cycle becomes variable • Ends 12 months after the last menstrual period (menopause) • Marked by light, irregular menses and wide variations in hormone levels • Alterations in responsiveness to gonadotropins and their secretion • Average onset age: 46 (39-51) • Average Duration: 5 years (2-8) • Usually occurs between age 40-50

6. Menopause • Permanent cessation of menses following loss of ovarian follicular activity • Retrospective Diagnosis: 12 months of amenorrhea occurring after menarche • Average age: 51 • Late: >55 • Early: 40-45 • Risk factors: smoking, short menstrual cycles, nulliparity, T1DM, Family Hx • Average duration: 5 (2-8)

7. Premature Ovarian Failure Onset of spontaneous menopause BEFORE the age of 40 Usually idiopathic or autoimmune If occurs <30 yo: chromosome studies to r/o genetic cause (mosaicism)

8. QUIZ A 35 yo woman complains of irregular menses over the past year. It has now been 13 months since her last cycle. She describes mood changes, feelings of inadequacy, vaginal dryness, difficulty sleeping with episodes of warmth and sweating that awaken her. Is this: Menopause Perimenopause Premature ovarian failure None of the above All of the above

9. Physiology of Menopause • Women are born with a set number of oocytes decreases continuously from conception • ~400-500 oocytes ovulated per lifetime • Continuous loss despite pregnancy, OCP, or anovulatory cycles • Menopause is the point at which no further oocytes are available to be recruited and ovulated (oocyte exhaustion).

11. Menopause Pathophysiology

13. Quiz A 52 yowoman complains of irregular menses over the past year. It has now been 13 months since her last cycle. She describes mood changes, feelings of inadequacy, vaginal dryness, difficulty sleeping with episodes of warmth and sweating that awaken her. Is this: Menopause Perimenopause Premature Ovarian Failure None of the above All of the above

14. Quiz What are signs and symptoms of menopause?

15. Clinical Presentation of Menopause SYMPTOMS • GU: • Amenorrhea, dyspareunia, vaginal dryness, mastodynia • Dysuria, urinary frequency/urgency, increased UTIs • Vasomotor Instability: • Hot Flashes, sweats, palpitations • Worse with stress/at night • Psychological: • Mood swings, depression, insomnia, irritability, anxiety • Loss of memory/concentration, loss of libido SIGNS: • vaginal uteral and cervical atrophy, atrophy of the breasts. • General loss of pelvic muscle tone vaginal prolapse

16. Reference: Blueprints Series Obstetrics and Gynecology, 2013

17. Long Term Consequences • Loss of protective benefits of estrogen: increased risk of CAD • Estrogen increases HDL and decreases LDL and protects against atherogenesis • Accelerated bone resorption: osteopeniaosteoperosis • Estrogen regulates osteoclast activity

18. NB: HOT FLASHES ≠ JOKE • Most common symptom of menopause • Vasodilation red flushing of chest, neck, face + sensation of heat • Sweating core heat loss cold/clammy sensation • Highly variable: • Occasional brief sensations of warmth vs • Hourly waves of heat, drenching sweat, red flushing of skin, increased HR • Associated sx: anxiety, irritability, panic, disrupted sleep, cognitive, psychological, and social dysfunction…

19. Hot Flashes The cause of hot flashes is unknown. They are thought to be due to thermoregulatory dysfunction, initiated at the level of the hypothalamus by estrogen withdrawal.

20. Quiz A 42 yo woman complains of irregular menses over the past year. It has now been 6months since her last cycle. She describes mood changes, feelings of inadequacy, vaginal dryness, difficulty sleeping with episodes of warmth and sweating that awaken her. She thinks she is going through menopause, but her mom didn’t go through menopause until she was 52 and her sister was just diagnosed with cancer. Are there any investigations you would to do help decide your management?

21. Investigations • FSH • Increased levels of FSH (>35 IU/L) on day 3 of cycle if still cycling • FSH not always predictive due to monthly variation • LH • FSH>LH • Estradiol • Decreased levels of estradiol occurs later

22. Investigations Others: • Inhibin B • progressively decreases in menopausal transition • AMH (antimullerian hormone) • a product of the granulosa cell, progressively decreases • AFC (Antral Follicle Count) • Follicles measuring between 2-10mm in diameter on transvaginal ultrasound, declines steadily from reproductive years through post menopause Inhibin B and AMH are used in straw staging *Not validated for the evaluation of menopausal status

23. Stages of Reproductive Aging Workshop (STRAW) staging system

24. And Blood Work to rule out other causes • Serum human chorionic gonadotropin (hCG) • If sexually active and not using reliable contraception • Prolactin • hyperprolactinemia • TSH • Thyroid disease

25. Again, but in break down by age • Under age 40 years • Premature ovarian failure evaluation • Estradiol (low), FSH (high), Tansvaginal US for AFC • Ages 40-45 years • Endocrine evaluation • B-hCG, prolactin, TSH • Over age 45 years • Menopause evaluation • Irregular menses and menopausal symptoms, no evaluation necessary • FSH can be misleading, use SWAN to stage • Consider B-hCG, if signs of if hyerprolactinemia or thyroid disease should evaluate these future

26. Quiz A 52 yo woman complains of irregular menses over the past year. It has now been 13 months since her last cycle. She describes mood changes, feelings of inadequacy, vaginal dryness, difficulty sleeping with episodes of warmth and sweating that awaken her. She finds the hot flashes very distressing and they are significantly impairing her everyday activities. Is there anything we can do to help?

27. Hormone Replacement Therapy Estrogen is the most effective treatment available for relief of menopausal symptoms, especially hot flashes. Estrogen alone or combined with progestin is currently indicated for treatment of moderate to severe hot flashes during menopause.

28. Risks of HRT Historically HRT was often prescribed to as it was thought to prevent coronary heart disease (CHD) and osteoporosis. However, data from the Women’s Health Initiative (WHI) Study showed adverse outcomes associated with estrogen-progestin therapy including increased risk of: Coronary Heart Disease Stroke Venous Thromboembolism Breast Cancer Benefits: Reduction of fractures and colorectal cancer

29. Limitations of the WHI Study This study included healthy postmenopausal women with a mean age of 63. The study clearly demonstrated adverse effects of HRT in older postmenopausal women (over 60), however, most women seek medical attention for new onset of menopausal symptoms. Therefore, the average age of those requesting HRT is women in their late 40’s and early 50’s. The risks of HRT are less well studied in this population.

30. Current Guidelines for HRT For women with moderate to severe vasomotor symptoms (and no history of breast cancer or heart disease) estrogen-progestin therapy can be used. Unopposed estrogen may be used in those who have had a hysterectomy. For women with vaginal atrophy only, vaginal estrogen is used. HRT should not be used for more than 5 years.

31. Other Options Non-hormonal pharmacologic options: Gabapentin SNRIs SSRIs Clonidine Nonprescription options: Soy Black cohosh Isoflavone supplements Vitamin E Lifestyle Modifications: Keep the core body temperature cool Regular exercise Maintain a healthy weight Smoking cessation

32. References Martin K.A., Barbieri R.L. (2014). Postmenopausal hormone therapy: benefits and risks. In P. Synder, W Crowley UpToDate. Available from: http://www.uptodate.com/contents/postmenopausal-hormone-therapy-benefits-and-risks?source=search_result&search=hormone+replacement+therapy&selectedTitle=1~150 Casper, R.F., Santen R.J (2014). Menopausal hot flashes. In R. Barbieri, W. Crowley UpToDate. Available from: http://www.uptodate.com/contents/menopausal-hot-flashes?source=search_result&search=hot+flashes&selectedTitle=1~150

33. References Obstetrics and Gynecology (Blueprints Series). Tamara Callahan and Aaron Caughey, Lippincott Williams & Wilkins 2013 www.SOGC.org Bachmann, GA. “Menopausal Vasomotor Symptoms: Causes, Effects, and Evidence-Based Treatment Options”. University of medicine and dentistry New Jersey. 2004