Menopause 2010

Katherine Beach, CNM

Maine Medical Partners

Women’s Health

Definition of Menopause

• Cessation of Menses for 12 consecutive months– Genetic factors– Lifestyle factors (smoking, alcohol abuse)– Long term health– Transition time is very individual

• Ranges from easy to very difficult

Age of Menopause

• Average age in the US is 51– Range is 42-58 years

• Average of 2 years earlier in smokers• Diagnosis is given retrospectively• Earliest clinical finding is a decrease in cycle

length– Age 18-30: 30 day cycles– Age 40: 25 day cycles– Age 45: 23 day cycles

Outline/Introduction

• Menopause as time of transition

• Health considerations– Cardiac disease– Loss of bone mass– Breast cancer

• Current understanding of hormone therapy

General Considerations

• Life expectancy is now 80 years– 30 years longer than in 1910

• One-third to One-half of life is post-menopause

• Public Health Impact– Cardiac disease– Osteoporosis

10 Leading Causes of Death

• Heart Disease• Cancer (Lung Ca in Maine)• Stroke• Chronic Respiratory Disease• Accidents/Unintentional Injuries• Diabetes• Alzheimer’s Disease• Influenza/Pneumonia• Nephritis/Kidney Disease• Septicemia

Peri-Menopause

• Defined as the years surrounding the final menstrual period

• Often characterized by hot flashes/night sweats

• Can be accompanied by mood swings, irritability

Counseling the Perimenopausal Woman

• Discuss changes in cycles

• Expectations

• Seek medical attention if:– Bleeding more frequently than every 21 days– Bleeding is heavy for more than 7 days– Hot flashes and/or insomnia are disturbing to

daily life

Terminology

• Natural/spontaneous menopause– The final period, confirmed after 12

consecutive months of amenorrhea with no obvious pathologic cause

• Induced menopause– Permanent cessation of menstruation after

bilateral oophorectomy or iatrogenic ablation of ovarian function

Terminology (continued)

• Premature menopause– Menopause reached at or under age 40, whether

natural or induced

• Premature ovarian failure– Ovarian insufficiency experienced under age

40, leading to permanent or transient amenorrhea

Perimenopausal Endocrine Changes

• Hypothalamic-ovarian axis– Inhibin levels decrease– Ovaries become resistant to pituitary FSH– This results in higher estradiol levels– Corpus luteum function decreases, leading to

shorter luteal phases and lower progesterone levels

– End result is shorter cycles with heavier bleeding

Initial Clinical Symptoms

• Hot flashes (75% of women in the US)– Sleep disturbances– Insomnia

• Vaginal dryness

• Irritability

• Mood swings

Multi-Organ Changes Due to Estrogen Loss

• Urinary and reproductive tracts

• Bone

• Vascular lining

• Skin

• Brain

• Central nervous system

• Teeth

Later Clinical Symptoms

• Osteopenia/Osteoporosis– Higher incidence if Caucasian or Asian descent

– Slender body build

– Positive family history

– Early estrogen deficiency

– Abuser of tobacco and/or alcohol

– Low calcium and Vitamin D intake

– Sedentary lifestyle

• Cardiac disease

Screening for Bone Density Loss

• Dual Energy X-Ray Absorptiometry (DEXA) is current standard of care

• Non-invasive

• Accurate

• Bone Density is measured in standard deviations from the norm

Diagnosis of Osteoporosis Using WHO Criteria

Normal T-score above –1

Osteopenia T-score between –1

and –2.5

Osteoporosis T-score of –2.5 or below

When to start screening and how often should it be done?

• Usually best to obtain baseline at time of menopause

• If normal, repeat in 5 years• If abnormal, recommend treatment and repeat in 2

years– For all women, Calcium 1500 mg/day and Vitamin D

1000 IU/day– Daily weight-bearing exercise

• Osteopenia vs Osteoporosis

Estrogens Produced by the Body

• Estradiol– Major estrogen secreted by the ovaries

• Estriol– Weak peripheral metabolite of estradiol and estrone

• Estrone– Minor estrogen secreted by the ovary and produced

from peripheral conversion of androstenedione

Who Should Use Hormone Therapy?

• Current thinking is to use HT to relieve hot flashes on a short-term basis (2-5 years) and at the lowest dose that will achieve the desired effect

• Should be initiated at the time of menopause, not many years after menopause

Women’s Health Initiative

• First Randomized Control Trial for Women– Not until 2002

• Primary objective was prevention of Cardiac Disease

• ET and EPT neither reduce nor increase incidence of cardiac disease

• Average age of women in study was 63 yrs• Data may not translate to more typical woman

seeking HT at age 50

WHI (continued)

• Also looked at Breast Cancer, Stroke, DVT, Dementia, Diabetes, Endometrial Cancer, Osteoporosis, and Depression with use of HT

• EPT arm of study was discontinued early

• ET arm continued

• On-going studies are continuing

Terminology

• ET—Estrogen Therapy

• EPT—Combined Estrogen-Progestogen Therapy

• HT—Hormone Therapy (includes both ET and EPT)

• Progestogen—Includes both natural progesterone and synthetic progestins

Local Estrogen Therapy for Vaginal Dryness

• Can be initiated safely at any time in a woman’s life

• 3 forms currently available– Estrogen cream (1 gram per vagina 1-2 times

per week)– Vagifem tablets (1 tablet per vagina once a

week)– Estring (1 ring per vagina every 3 months)

Vaginal Estrogen Treatment

• Local effect, not systemic– Does not increase risk of cardiac disease,

stroke, breast cancer, or DVT– Relieves dyspareunia (painful intercourse) that

is due to vaginal atrophy– Will not improve decreased libido– May benefit urge incontinence– May reduce risk of recurrent UTIs

Systemic Hormone Therapy

• Must use both estrogen and progesterone if uterus is intact to protect endometrium

• Estrogen alone will cause hyperplasia and can lead to uterine cancer

• Safe to use estrogen alone if uterus is absent

• At usual doses, does not affect weight or Body Mass Index

HT and Quality of Life

• Must weigh risks and benefits

• HT can improve health-related QOL through mood elevation and decreased menopause symptoms

• Less fatigue (as result of better sleep) often leads to fewer mood swings and less irritability

HT and Osteoporosis

• Not first line of therapy• Should use bisphosphonates if possible

– Fosamax– Actonel– Boniva

• If bisphosphonates are not tolerated (GI upset) can use HT, but patient must understand risks

• Osteoporosis is long-term problem—cannot be addressed with 2-5 year therapy in most cases

HT & Cardiac Disease

• HT may reduce cardiac disease risk if initiated in younger and more recently postmenopausal women

• Follow-up studies from WHI show longer HT duration may be associated with less mortality in women who initiate therapy at time of menopause and continue use beyond 5 years

HT & Cardiac Disease (continued)

• HT not recommended for women who have gone through menopause more than 5 years ago

• Even short-term use in this group of women is associated with increased risk of cardiac disease

• HT currently not recommended as sole or primary indication for coronary protection in women of any age

Stroke & Venous Thromboembolism

• Systemic HT increases risk of ischemic stroke and therefore HT is not recommended for primary or secondary prevention of stroke

• Oral HT increases risk of VTE in women over age 60

• VTE risk emerges soon after HT initiation (1-2 years) and decreases over time

• Possible lower risk with transdermal patch than with oral HT, but no RCT evidence

HT & Diabetes Mellitus

• HT reduces new DM onset

• Inadequate evidence to recommend HT for sole or primary indication of DM prevention in peri- or postmenopausal women

• Transdermal ET may have advantages over oral route in women with DM

HT & Breast Cancer

• Breast cancer risk increases with HT use beyond 5 years

• Increased absolute risk of EPT in WHI was rare (4-6 cases/10,000 women/yr of EPT for >5 years)

• WHI ET trial showed no increased risk after 7.1 years (6 fewer cases/10,000 women/yr of ET use; not statistically significant)

HT & Breast Cancer (continued)

• EPT and, to a lesser extent, ET, increase breast cell proliferation, breast pain, and mammographic density

• EPT may impede diagnostic interpretation of mammograms

• HT not recommended if personal history of breast cancer

• Evidence unclear when family history of breast cancer exists (no RCTs)

HT & Mood/Depression

• Progestogens in EPT may worsen mood if woman has a history of premenstrual syndrome, premenstrual depressive disorder, or clinical depression

• Controversial if ET augments antidepressant effects of SSRIs (selective serotonin re-uptake inhibitors)

HT & Dementia

• HT not recommended at any age for the prevention of dementia

• HT seems to increase dementia if initiated at age 65 or older

• Inadequate data as to whether HT started soon after menopause increases or decreases later dementia risk

• Limited data do not support HT for prevention of Alzheimer’s disease

HT & Premature Menopause, Premature Ovarian Failure

• Most data suggest HT has protective cardiac effect in these women

• Data regarding HT in women experiencing menopause at the typical age cannot be extrapolated to these women

• Likely that risks attributable to HT are smaller and benefits greater in these younger women, but no RCTs exist

HT & Total Mortality

• HT may reduce total mortality when initiated soon after menopause

• Both ET and EPT may reduce total mortality by 30% when initiated in women <60 years old

• HT not associated with mortality reduction among women who initiate HT at >60 years old

HT Dosages

• Therapeutic goal is lowest effective estrogen dose (plus corresponding low progestogen dose for women with a uterus) consistent with individual treatment goals, benefits, and risks

• Lower doses better tolerated, may have more favorable benefit-risk ratio than standard doses

HT Dosages (continued)

• Estrogen– 0.3 mg oral conjugated estrogens

– 0.5 mg oral micronized 17ß-estradiol

– 0.014-0.025 mg 17ß-estradiol patch

• Progestogen– 1.5 mg oral medroxyprogesterone acetate

– 0.1 mg oral norethindrone acetate

– 0.5 mg oral drospirenone

– 50-100 mg oral micronized progesterone

HT Routes of Administration

• No clear benefit of oral vs. transdermal if no risk factors

• Transdermal bypasses the liver, and therefore is recommended for women with liver disease

• Transdermal ET may be associated with lower DVT risk than oral route

• Local ET preferred when solely vaginal symptoms• Systemic progestogen required for endometrial

protection from unopposed systemic ET

Bioidentical Hormone Therapy

• Custom-made HT compounded in accordance with healthcare provider’s prescription

• Custom BHT may provide doses, ingredients, and routes of administration not commercially available– Apothecary By Design

• Salivary hormone testing used to adjust custom BHT levels is not justified on any scientific basis

Evaluation Prior to HT Initiation

• Complete history and physical exam

• Mammography within the 12 months before HT initiation and yearly while on HT

• DEXA as needed

• After discussion of risks and benefits, begin therapy as close to menopause as possible

• Never begin therapy in women over age 60

Individualization of Therapy

• Imperative to review risk profile• Each woman must be informed of her

known risks• Acceptance of HT risks varies with the

individual• Acceptance of HT risks varies as to primary

indication (e.g. relief of hot flashes now vs. prevention of osteoporosis later in life)

Duration of Use

• Again, must individualize for each woman

• Review risk/benefit ratio each year

• Use lowest effective dose

• May continue for further osteoporosis prevention/treatment if alternate therapies are not acceptable

• Must have clinical supervision

When HT is Discontinued…

• 50% chance of symptoms recurring

• Hot flashes are similar whether tapered or abrupt discontinuance

• Data conflicting regarding breast cancer incidence after discontinuance

• Decision to resume HT must be individualized

Explaining Risk

• Essential to understand basic concepts of risk and be able to explain to patients

• Tailor the discussion to the individual patient• Be sensitive to whether she wants numerical

information, your honest opinion, or both• Providing figures for absolute risk is clearer than

relative risk• Put the risk is perspective (ie, a risk is “rare” if it

occurs <10 per 10,000 patients per year, it’s “very rare” if it occurs <1 per 10,000 patients per year)

Explaining Risk (continued)

• Potential absolute risks for use of HT are low, especially for ET in WHI

• In WHI, risks for EPT were “rare”, except for stroke• For younger women (<50 yrs) or those at low risk of

cardiac disease, osteoporosis, breast cancer, or colon cancer, absolute risk is likely to be even smaller than seen in WHI

• Each regimen, route of administration, and timing of therapy has distinct beneficial and adverse effects

HT Risk is Related to…

• A woman’s baseline disease risks• Her age• Age at menopause• Cause of menopause• Time since menopause• Prior use of any hormone• HT types, routes of administration, and doses used• Emerging medical conditions during treatment

Summary

• Menopause is a retrospective diagnosis

• We serve women best if we individualize discussion and treatment based on symptoms and risk factors

• Ideal world—few symptoms, and no need for any hormone replacement therapy

• As women’s life expectancy continues to increase, must look at menopause as third phase of life, and optimize health