Menopause Basics Physiology, Perimenopause and Menopause JoAnn V. Pinkerton, MD Director, Midlife Health Center Professor of Ob/Gyn University of Virginia 2007 Menopause Basics Learning Objectives: Describe the hypothalamic-pituitary-ovarian axis Differentiate between Perimenopause and Menopause Learn physiologic and anatomic changes at menopause Describe typical menopausal symptoms
Perform focused history +physical for menopausal woman Interpret selected laboratory tests to evaluate menopause. Counsel patients regarding female sexuality and aging physical, emotional, and relationship-based issues What does menopause mean to women?
Cessation of menstrual periods End of reproductive capacity Hormonal changes Change of life, a life stage End of prior symptoms Beginning of new symptoms Changing emotions Changing body Aging process Disease risks Medical care needs Woods et al. Menopause 1999. Menopause: The Reality
Clinical diagnosis Permanent cessation of menses following the loss of ovarian activity Lack of menses for 12 months Mean age in US is 51 (45-55 years) Women will spend one-third to one-half of their lives postmenopausally Katz VL, Lentz GM, Lobo RA, Gershenson DM. Comprehensive Gynecology. 5th ed. Philadelphia, PA: Mosby; 2007 STRAW Menopause
The anchor point that is defined after 12 months of amenorrhea following the final menstrual period (FMP), which reflects a near complete but natural diminution of ovarian hormone secretion. Soules et al. Menopause 2001. CA MS Natural (spontaneous) menopause
Occurs after 12 consecutive months of amenorrhea, for which there is no other obvious pathologic or physiologic cause. Utian. Climacteric 1999. (Average age in Western world is 51 years) CA MS Premature menopause Menopause that occurs in women at or under 40 years old.
Utian. Climacteric 1999. Premature ovarian failure Hypergonadotropic amenorrhea 40 years old Associated with many other health conditions (eg, autoimmune, toxic, genetic) May not be permanent Is not the same as menopause premature Premature ovarian failure (continued)
Ovarian insufficiency leading to amenorrhea that occurs in women 40 Can be transient (eg, from overexercising, eating disorders, high stress levels Can be permanent (eg, from autoimmune disease or genetic abnormalities) and equivalent to premature menopause STRAW reproductive aging system Length decreases -2 days
Stages of Reproductive Aging Workshop. Menopause 2001. Symptoms of perimenopause Natural, normal changes, not a disease Subtle hormonal changes during the 30s Symptoms noticeable during the 40s Disturbances may be acute or gradual Not all midlife symptoms are attributable to menopause CA MS Induced menopause
Cessation of menstruation that follows bilateral oophorectomy (surgical menopause), iatrogenic ablation of ovarian function by chemotherapy or pelvic radiation therapy. Utian. Climacteric 1999. (No perimenopause transition for these women) Premature or induced menopause: complicating factors Early loss of fertility More severe symptoms Greater risk of osteoporosis and CVD
Possibly complicated by sequelae of underlying disease Little research regarding benefits/risks of treatment Hypothalamic-pituitary-ovarian axis Pituitary GnRH (+) LH FSH Inhibins Ovary
Hypothalamus Estradiol Progesterone Reproductive aging 1-2 million follicles at birth, only approximately 1,000 by menopause Most follicular loss due to atresia, not ovulation Atresia accelerates at around age 37 Age-related uterine changes also contribute to decreased fertility Ovarian function in perimenopause
Ovaries begin decreasing in size Estradiol still dominant estrogen Number of follicles decreases substantially Production of inhibin decreases Remaining follicles respond poorly to elevated FSH and LH Erratic ovulation results in menstrual cycle irregularity Decline in fertility
Fertility wanes starting at about age 37, before perimenopause signs occur By age 45, risk of spontaneous miscarriage increases to 50% Fertility-enhancing techniques available Natural pregnancy still possible until menopause is reached Physiology: perimenopause Estrogen and progesterone levels fluctuate erratically Very high serum estrogen levels may result Gradual decline in testosterone with age beginning mid-30s Zumoff et al. J Clin Endocrinol Metab 1995.
Burger et al. J Clin Endocrinol Metab 2000. Serum hormone levels at menopause Circulating estrogens Ratio of estrogen to androgen Sex hormone-binding globulin secretion Peripheral aromatization of DHEA to estrone Reversal of E2 to E1 ratio No significant change in testosterone levels E, FSH, and inihibins prior and following FMP
Burger et al. J Clin Endocrinol Metab 1999. Health evaluation at perimenopause Determine the primary complaint(s) Medical, psychological, and social history Family history Complete physical examination Determine quality of life Laboratory tests For differential diagnosis of problems Screening tests for specific chronic conditions Routine screens
Standard blood screens Periodic serum cholesterol (total, HDL, LDL, TG) Fasting glucose Thyroid screen Annual Pap test Periodic stool guaiac test, sigmoidoscopy, colonoscopy
Annual mammogram Urine screen, when indicated Sexually transmitted infections, when indicated Bone density, when needed Evaluate need contraception Proportion of Allfor U.S. Unintended Pregnancies Age: 1994 Proportion of all US unintendedby
pregnancies by age: 1994 Unintended Pregnancies Unintended pregnancies Unintendedpregnancies Pregnancies Ending in Abortion Unintended ending in abortion Percent
100 90 80 70 60 50 40 30 20 10 0 Less than 15 15-19
20-24 25-29 Age (years) 30-34 35-39 40 and older Henshaw. Fam Plann Perspect 1998. Confirming menopause
Age, medical/menstrual history, and symptoms usually sufficient Rule out other causes of symptoms (eg, thyroid disorder) Consistently elevated FSH (> 30 mIU/mL) diagnostic, but rarely necessary except with nonsurgically induced menopause Serum estradiol testing may be of value; value of salivary levels unproven Evaluate risk for specific conditions and diseases
Vasomotor symptoms/sleep disturbance Vulvovaginal health Psychological health Cardiovascular disease Diabetes Osteoporosis Cancer
Sexual function Sexually transmitted infections Urinary incontinence Alcohol/drug use/abuse Domestic abuse/violence risk Assess all women for alterable risk factors Smoking Poor diet
Obesity Lack of exercise Stress Habit-forming drugs Unsafe sex Excess alcohol No seat belts Therapeutic options No intervention/treatment
Lifestyle modification Nonprescription remedies Complementary and alternative medicine (CAM) approaches Prescription drugs Surgical procedures Write a lifestyle Rx Stop smoking Have a nutritionally sound diet Achieve and maintain healthy weight Reduce stress Avoid excess alcohol Say no to drugs and unsafe sex Wear seat belts Exercise regularly
Benefits of regular exercise Decreases hot flashes Improves mood and sleep Decreases/maintains weight Supports joint/muscle flexibility Prevents bone loss Decreases risk of many other diseases Improved control of behavioral risk factors, such as use of tobacco, alcohol, and other drugs, lack of exercise, and poor nutrition, could prevent half of premature deaths, one-third of all cases of acute disability, and all cases of
chronic disability. US Preventive Services Task Force. Guide to Clinical Preventive Service 1989. Vasomotor symptoms One of the hallmarks of perimenopause Includes hot flashes and night sweats Recurrent, transient episodes of flushing, perspiration, and intense warmth on upper body and face Skin temperature increases 1-7 C, returns to normal gradually Chill often follows Causes of hot flashes Precise cause is unknown Estrogen levels alone not predictive
of hot flash frequency or severity Other conditions: thyroid disease, epilepsy, infection, insulinoma, carcinoid syndromes, leukemia, pancreatic tumors, autoimmune disorders, mast-cell disorders Hot Flushes May Continue Years After Menopause Number of Subjects 50 Ages 29 to 82 Years
45 40 35 30 Number of years women report having hot flushes as estimated by a survey of 501 untreated women who experienced hot flushes 25 20 15 10 5 0 0
1 2 3 4 5 6 7 8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 28 29 30 32 36 38 41 44 Years Mean age of natural menopause was 49.5 years; mean age of surgical menopause was 43.7 years. Kronenberg F. Ann NY Acad Sci. 1990;592:52-86. Used with permission. 33 Causes of hot flashes (continued) Drugs: tamoxifen, raloxifene Lifestyle factors: warm ambient air temperature, higher BMI, cigarette smoking, less physical activity
Hot Flashes: Demographics, Lifestyle, Health Symptoms vary by race/ethnicity More African Americans and Hispanics than Caucasians affected Fewer Chinese than Caucasian affected Significant association with BMI Passive smoke exposure History of premenstrual symptoms Use of OTC pain medication History of comorbidities Perceived stress Age Gold EB et al. Am J Epidemiol. 2004;159(12):1189-1199
Alternative Approaches for Vasomotor Symptoms: Lifestyle Adaptations Guidelines from NAMS Limited effectiveness Cooling body core temperature Exercise Paced respirations (catecholamine control) Relaxing activities yoga, massage, meditation, paced respiration, leisurely bath Avoid Triggers spicy food, hot drinks, caffeine, alcohol NAMS Position Statement (Treatment of menopause-associated vasomotor symptoms) Menopause. 2004;11:11-33; Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-813 Huntley AL, Ernst E. Menopause. 2003;10:465-76.
Non-Prescription Remedies Side effects and drug interactions clearly occur Lack long-term safety and efficacy data Phytoestrogens/isoflavones Dietary or supplements (soy-derived) Red clover Black cohosh Vitamin E - not clinically significant Studies show no effect compared with placebo Dong quai Ginseng Evening primrose oil
NAMS Position Statement (Treatment of menopause-associated vasomotor symptoms). Menopause. 2004;11:11-33; Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-813; Huntley AL, Ernst E. Menopause. 2003;10:46576. Clinical Management Mild Vasomotor Symptoms For mild vasomotor symptoms Encourage lifestyle changes Non-prescription remedies- tested short term with little efficacy over placebo but no evidence of harm Dietary isoflavones Black cohosh Vitamin E Clinical Management Mod-Severe Vasomotor Symptoms Hormone therapy is only FDA approved
treatment gold standard SSRIs and gabapentin have efficacy in early studies Progestogens effective however large doses required Clonidine (oral or transdermal) Lifestyle Issues in Menopause
Vasomotor (hot flushes and night sweats) Low libido/painful intercourse Weight gain Memory problems, difficulty concentrating Mood swings Insomnia, fatigue Dizziness, rapid irregular heartbeat Atrophic vaginitis, bladder irritability Headaches Rapkin AJ. Am J Obstet Gynecol. 2007;196(2):97-106. OCs:
noncontraceptive benefits Suppress vasomotor symptoms Restore predictable menses Decrease dysmenorrhea Enhance BMD Prevent endometrial and ovarian malignancies OCs: when to stop FSH testing not reliable in perimenopausal women or in those using OCs If contraception needed, continuation to mid-50s reasonable Otherwise, consider stopping early 50s Low-dose OC has more hormone
EPT than Depression or Menopause? Depression Depressed1,2 Irritable1,2 Anhedonia1,2 Thoughts of death1,2 Worthlessness1,2 Menopause Energy2 Concentration2
Hot flushes1 Sleep2 Perspiration1 Weight change1 Libido1 1. Soares CN, Cohen LS. CNS Spectrums. 2001;6:167-174. 2. Joffe H et al. Psychiatr Clin North Am. 2003;26:563-580. Vaginal dryness1 Sleep disturbances
1/3 - 1/2 of US women aged 40-54 report sleep problems Occur mainly in women with nighttime hot flashes Most adults require 6-9 hr sleep nightly Potential causes: ovarian hormone changes, advancing age, onset of sleep disorders (eg, apnea), stress, painful chronic illnesses (eg, arthritis), other conditions (eg, CVD, allergies), drugs (eg, thyroid medication) Insomnia produces fatigue, irritability, chronic illness (eg, CVD), mood disorders (eg, depression) Improve sleep hygiene
Lower light and noise Adjust temperature (cool preferred) Avoid heavy evening meals Avoid alcohol, caffeine, nicotine throughout the entire day Exercise daily, but not close to bedtime Use bedroom only for sleep and sexual activities Have a regular sleep schedule, even on weekends
Use relaxation techniques ET effects on sleep Decreases frequency of Night sweats1-4 Periods of wakefulness during the night 3,4 Reduces sleep latency 1,2 Improves sleep in menopausal women with insomnia, even in the absence of vasomotor symptoms4 Increases the percentage of REM sleep 2,5 For EPT, use bedtime dosage of progesterone, a mild soporific, to improve sleep Scharf et al. Clin Ther 1997. 2 Schiff et al. Maturitas 1980.
1 Erlik et al. JAMA 1981. Polo-Kantola et al. Am J Obstet Gynecol 1998. 5 Antonijevic et al. Am J Obstet Gynecol 2000. 3 4 Uterine bleeding changes during perimenopause Strong predictor of perimenopause About 90% of women have 4-8 years of cycle changes before reaching menopause No universal definition of irregular but unique to each woman
Possible changes: lighter bleeding (avg blood loss, < 20ml) heavier bleeding (avg blood loss, > 40ml) bleeding lasting for < 2 days or > 4 days cycle length < 7 days or > 28 days skipped periods Bleeding during postmenopause Must be assessed Vaginal causes Uterine fibroids Endometrial or endocervical polyps Uterine or cervical malignancy EPT
Diagnostic workup for AUB Comprehensive history and pelvic exam Blood tests Endometrial biopsy Vaginal ultrasound Additional tests, such as sonohysterogram or hysteroscopy Presenting genital symptoms and physical signs of vaginal atrophy Symptoms Dryness Itching Burning Dyspareunia
Burning leukorrhea Vulvar pruritus Feeling of pressure Yellow malodorous discharge Signs on physical exam Pale, smooth, or shiny vaginal epithelium Loss of elasticity or turgor of skin Sparsity of pubic hair Dryness of labia Fusion of labia minora Introital stenosis Friable, unrugated epithelium Pelvic organ prolapse
Rectocele Vulvar dermatoses Vulvar lesions Vulvar patch erythema Petechiae of epithelium Bachmann et al. Am Fam Physician 2000. Physiology of Vulvovaginal Changes: Structure and Histology Loss of collagen and adiposity in vulva1 Clitoral glans loses protective covering2 Vaginal surface thinner,
less elastic; more friable2 Oriba HA, Maibach HI. Acta Derm Venereol. 1989;69:461-5. Bachmann GA, et al. In: Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. 2nd ed. 1999:195-201. 1 2 Non-Rx therapies for vaginal dryness Vaginal moisturizers effective; also produce low pH to guard against infection Vaginal lubricants ease penetration Avoid use of petroleum-based products Douches may worsen condition; antihistamines may have drying effect Continued sexual activity and/or
stimulation may benefit vaginal health ET and vulvovaginal atrophy Local estrogen appears at least as effective as systemic ET If genital atrophy present without vasomotor symptoms, nonsystemic therapy preferred Stimulation of endometrium observed with high doses, some advise adding progestogen1 1 NAMS Position Statement. Menopause 2004. Improvement in vaginal
cytology with local CEE Baseline Cycle 1 Open-label, single-treatment group, outpatient study N = 105 women with data valid for efficacy analysis Treatment significantly increased superficial and intermediary cells and decreased parabasal cells (P < .05) Raymundo et al. International Federation of Gynecology and Obstetrics 2000. Traditional sex response cycle Plateau Orgasm
Sexual excitement and tension Arousal Reduction Desire Time Kaplan. The New Sex Therapy: Active Treatment of Sexual Dysfunctions 1974. Sexual Response: Male vs Female Female sexual dysfunction: definition and classification International Consensus Development Conference on Female Sexual Dysfunction
I. Sexual desire disorders hypoactive sexual desire disorder sexual aversion disorder II. Sexual arousal disorder III. Orgasmic disorder IV. Sexual pain disorders dyspareunia vaginismus noncoital sexual pain disorder Basson et al. J Urol 2000. Female sexual dysfunction Affects 20% to 50% of women1 Multidimensional and multicausal combining
biological, psychological, and interpersonal factors1 Physically and emotionally distressing, and socially disruptive1 Increases with age2 Must cause distress to be a dysfunction Basson et al. J Urol 2000. 2 Goldstein. Int J Impot Res 2000. 1 Effect of perimenopause on parameters of sexual functioning Cross-sectional data reported from longitudinal, population-based Australian cohort, 45-55 yrs
Sexual responsivity Sexual frequency Libido Vaginal dyspareunia Partner problems Dennerstein et al. Obstet Gynecol 2000. Physician-Patient Communications Concerning Sexual Problems May Not Be Optimal If You Wanted to Talk to Your Doctor About a Sexual Problem, How Concerned Would You Be About the Following? There Would Be No Medical Treatment for Your Problem 46
Your Doctor Would Dismiss Your Concerns and Say It Was All Just in Your Head 30 51 20 76 71 Very Concerned
Somewhat Concerned Your Doctor Would Be Uncomfortable Talking About the Problem Because It Was Sexual in Nature 46 0 20 23
40 60 68* 80 100 Percentage *Numbers do not add up because of rounding; n = 500. Bennett, Petts & Blumenthal. National Survey of American Adults 25 and Older. Washington, DC: March 1999. Marwick C. JAMA. 1999:281:2173-4. Used with permission. Sexual history sample questions Are you sexually active?
Are you having any sexual difficulties or problems at this time? Have you noted any change in your sexual interest? Are you having any difficulty with vaginal lubrication? Do you have any concerns about your sexual health? Bachmann et al. Obstet Gynecol 1989. Model of complete clinical care Communication Tasks Opening
Engage Empathize Find It Educate Enlist 63 Fix It Closing Biomedical Tasks
Criteria for Informed Decision Making 1. 2. 3. 4. 5. 6. 7. Discussion of patients role in decision making Discussion of clinical issue or nature of decision Discussion of alternatives Discussion of the pros and cons of alternatives Discussion of uncertainties of decision
Assessment of patient understanding Exploration of patient preference Source: Braddock CH et al. J Gen Intern Med. 1997;12(6):339-345
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