By 2010, 45% of American women will be over age 50

1. By 2010, 45% of American women will be over age 50 Natl Center for Health Statistics

2. Perimenopausal Transition Years 100 75 50 25 0 Reproductive Years Postmenopause Women (%) 30 35 40 45 50 55 60 Age (years)

3. Changes Prior to Menopause •  Anovulatory cycles •  or  Menstrual cycle length •  FSH level (day 3) •  Inhibin B

4. Perimenopause • Time of transition characterized by unstable endocrine physiology and highly variable, unpredictable hormone profiles1 • Although cycle length begins to shorten, potential for ovulation and pregnancy is preserved for a number of years1,2 1. Klein NA, Soules MR. Clin Obstet Gynecol. 1998;41:912-920. 2. Munster K et al. Br J Obstet Gynaecol. 1992;99:422-429.

5. The Perimenopausal Transition: Endocrine Changes Mean Circulating Hormone Levels FSH & LHIU/L Estradiol Estrone pg/mL Menopause 80 FSH 70 LH 60 50 200 Estradiol 40 160 30 120 20 80 10 40 0 0 44 46 48 50 52 54 56 58 Age (years) Adapted from Speroff, Glass, and Kase. Clinical Gynecology and Endocrinology. 6th ed. Williams & Wilkins;1999:653.

6. Changes Associated WithDeclining Estrogen Concentrations • Hot flushes • Urogenital atrophy • Mood changes • Changes in cognitive function • Bone loss • Changes in skin appearance • Increase in risk of cardiovascular disease • Physiologic changes of the eye

7. Early phase Breast tenderness Irregular menstruation Irritability Loss of sense of wellness Hot flashes/night sweats Sleep disturbance Late phase Cognitive dysfunction Irregular and abnormal flow Sexual dysfunction Somatic symptoms increase Symptoms

8. When Does Perimenopause Occur? Average 1 Range* Age of Onset (y) 46 39-51 Duration (y) 3.8 2 2-8 *95% of women. 1 Adapted from Speroff, Glass, and Kase. In: Clinical Gynecology and Endocrinology. 6th ed. Williams & Wilkins;1999:653. 2 McKinley Maturitas 1992; 14: 103-115

9. Age of Menopause Median age of natural menopause (y)1,2 Overall 51.1-51.4 Smokers 1 to 2 years younger Likelihood of being menopausal by1,2 Age 50 y ~30% Age 55 y* 80% *May be more appropriate than age 50 for OC discontinuation. 1. Stanford JL et al. J Chron Dis. 1987;40:995-1002. 2. McKinlay SM et al. Ann Intern Med. 1985;103:350-356.

10. Menstrual Cycle Changes:Hallmark of Perimenopause

11. Changes in Cycle Length During Perimenopause Menstrual Cycle Length Shortens 35 Mean 5th, 25th, 50th, 75th, and 95th centile values 30 Cycle Length (days) 25 15 20 25 30 35 40 45 Age (years) Adapted from Munster K et al. Br J Obstet Gynaecol. 1992;99:422-429.

12. Menstrual Cycle Changes:Hallmark of Perimenopause • Usually shorter cycle length (eg, by 2 to 7 days) • longer or irregular less common • Changes in quality • Heavier initially, then lighter • Spotting prior to menses Adapted from Nachtigall LE. Clin Obstet Gynecol. 1998;41:921-927.

13. Vasomotor InstabilityDuring Perimenopause “Hot flashes are one of the chief menopausal complaints for which women in Western societies seek medical treatment.” 1 1. Kronenberg F. Ann N Y Acad Sci. 1990:592:52-86.

14. Vasomotor InstabilityDuring Perimenopause • ~ 85% of perimenopausal women experience vasomotor instability • hot flushes, night sweats, sleep disturbances • Intensity, duration, and frequency highly variable • 1-2 to 40 flushes/day Nachtigall LE. Clin Obstet Gynecol. 1998;41:921-927.

15. Menstrual Status % Reporting Hot Flashes Premenopausal* ~10 Perimenopausal† ~30 – 85% Recently postmenopausal ~20 – 90% 4 years postmenopause ~20 – 60% Vasomotor InstabilityDuring Perimenopause • * Menstruation within the 3 prior months with no change in regularity of cycle. • †3 to 11 months of amenorrhea or increased menstrual irregularity. • McKinlay SM et al. Maturitas. 1992;14:103-115. • Kronenberg F. Ann N Y Acad Sci. 1990:592:52-86. • Nachtigall LE. Clin Obstet Gynecol. 1998;41:921-927

16. Serum Concentrations of Ovarian Hormones Ovaries produce more androgen than estrogen.

17. Consequences of MenopausalHormone Deficiency Last period Menopause symptoms Sexual complaints Urogenital atrophy and symptoms Vascular and heart disease Bone loss/osteopenia Osteoporosis 40 45 90+ 50 55 60 65 70 75 80 85 Age (year)

18. Hot flushes/night sweats Palpitations Sleep disturbance Chest pressure Shortness of breath Headaches Numbness Fatigue Weakness Joint pain Decreased sexual desire Vaginal dryness and painful intercourse Loss of urinary control Memory loss Anxiety Depression The Menopausal Syndrome

19. Severity 0 Absence 1 2 3-4 5-6 Moderate/Severe 100 75 50 25 0 Reporting Complaints (%) <1 1-3 3-6 6-12 1 2 3 4 5 6-7 8-10 >10 Regular menstrual bleeding Pre/perimenopause(months since last menstrual bleeding) Postmenopause (years since last menstrual bleeding) Prevalence of Vasomotor Complaints Oldenhave A, et al. Am J Obstet Gynecol. 1993;168:772-780.

20. Genital Irritation, burning, pruritus Leukorrhea Dyspareunia Decreased vaginal secretions Shortening/lessening of vaginal distensibility Urinary Frequency, urgency Dysuria Nocturia Incontinence* Genitourinary Symptoms Associated With Menopause *Controversial.

21. Vaginal Cytology Premenopause Postmenopause

22. 2.0 Vaginal tablets E2 25 g (n = 80) Vaginal cream CEE 1.25 mg (n = 79) 1.5 Mean Composite Scores 1.0 0.5 0.0 0 2 12 24 Weeks of Treatment Vaginal symptoms score: 0 = none, 1 = mild, 2 = moderate, 3 = severe Effect of Estrogen on Vaginal Symptoms E2 = 17 ß-estradiol; CEE = conjugated equine estrogens. Rioux JE, et al. Menopause. 2000;7:156-161.