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

Natl Center for Health StatisticsNatl Center for Health Statistics

Perimenopausal Transition Years100

75

50

25

0

30 35 40 45 50 55 60

Age (years)

PostmenopauseReproductive

Years

Wom

en (

%)

Changes Prior to Menopause

Anovulatory cycles

or Menstrual cycle length

FSH level (day 3)

Inhibin B

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.

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

The Perimenopausal Transition: Endocrine Changes

Mean Circulating Hormone LevelsMean Circulating Hormone Levels

Adapted from Speroff, Glass, and Kase. Clinical Gynecology and Endocrinology. 6th ed.Williams & Wilkins;1999:653.

8070

6050403020100

FSH &LHIU/L

EstradiolEstronepg/mL

2001601208040

044 46 48 50 52 54 56 58

Age (years)

Menopause

FSH

LH

Estradiol

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

Symptoms

• 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

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

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.

Menstrual Cycle Changes:

Hallmark of Perimenopause

Changes in Cycle Length During Perimenopause

Menstrual Cycle Length ShortensMenstrual Cycle Length Shortens

35

30

25

15 20 25 30 35 40 45

Age (years)

Mean

5th, 25th, 50th, 75th,and 95th centile values

Cyc

le L

eng

th(d

ays)

Adapted from Munster K et al. Br J Obstet Gynaecol. 1992;99:422-429.

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.

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.

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.

Menstrual StatusMenstrual Status % Reporting Hot Flashes% Reporting Hot Flashes

PremenopausalPremenopausal** ~10 ~10

PerimenopausalPerimenopausal†† ~30 – 85% ~30 – 85%

Recently postmenopausalRecently postmenopausal ~20 – 90%~20 – 90%

4 years postmenopause4 years postmenopause ~20 – 60%~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.1. McKinlay SM et al. Maturitas. 1992;14:103-115.2. Kronenberg F. Ann N Y Acad Sci. 1990:592:52-86.3. Nachtigall LE. Clin Obstet Gynecol. 1998;41:921-927

Serum Concentrations of Ovarian Hormones

Premenopause (mean) Postmenopause (mean)

Estradiol (pg/mL) 50-400 8-35 (<25)

Estrone (pg/mL) 30-300 20-60

Testosterone (ng/dL) 20-50 (35) 30

Androstenedione (ng/dL) ~130 ~50

Ovaries produce more androgen than estrogen.

Consequences of MenopausalHormone Deficiency

Last period

Age (year)

Bone loss/osteopenia

40 90+45 5550 60 65 70 75 80 85

Menopause symptoms

Sexual complaints

Urogenital atrophy and symptoms

Vascular and heart disease

Osteoporosis

• 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

Prevalence of Vasomotor Complaints

Oldenhave A, et al. Am J Obstet Gynecol. 1993;168:772-780.

Severity

0 Absence

1

2

3-4

5-6 Moderate/Severe

100

75

50

25

0

Regular menstrual bleeding

Pre/perimenopause(months since last

menstrual bleeding)

Postmenopause (years since last menstrual

bleeding)

<1 1-3 3-6 6-12 1 2 43 5 6-7 8-10 >10

Rep

orti

ng

Com

pla

ints

(%

)

Genitourinary Symptoms Associated With Menopause

Genital

• Irritation, burning, pruritus

• Leukorrhea

• Dyspareunia

• Decreased vaginal secretions

• Shortening/lessening of vaginal distensibility

Urinary

• Frequency, urgency

• Dysuria

• Nocturia

• Incontinence*

*Controversial.

Vaginal Cytology

Premenopause Postmenopause

Effect of Estrogen on Vaginal Symptoms

E2 = 17 ß-estradiol; CEE = conjugated equine estrogens.

Rioux JE, et al. Menopause. 2000;7:156-161.

Vaginal symptoms score: 0 = none, 1 = mild, 2 = moderate, 3 = severe

0.0

0.5

1.0

1.5

2.0

0 2 12 24

Mea

n C

omp

osit

e Sc

ores

Weeks of Treatment

Vaginal tablets E2 25 g (n = 80)

Vaginal cream CEE 1.25 mg (n = 79)