Post on 24-Dec-2015
Menopause
Division of Urogynecology and Reconstructive Pelvic Surgery
Department of OB/GYN
Epidemiology
Average age is 51.4 years 95% confidence interval of Bell Curve gives a range of 45-
55 years. Less than 2% occur before age 40. Factors associated with early menopause
– Cigarette smoking (1.5 yrs earlier)– History of short intermenstrual interval– Family history– Chemo / Radiation / Genetic factors
Unrelated to number of prior ovulations, pregnancies, use of OCPs, height, weight, age at menarche, race, class or education
Elderly Population
In 2000, life expectancy:– Women 79.7 years– Men 72.9 years
Once you reach 65:– Women expect to live until 84.3 years old– Men expect to live until 80.5 years old
Therefore, more than 1/4 of a woman’s life is spent in menopause
Peri-menopause
Peri-menopause– Transitional period
Hallmark is menstrual irregularities– Shortened cycle length– Skipped cycles– 10% of women will have abrupt cessation of menses
Median length of 4-5 years
– Median age of onset is 47.5 years
Physiology
General feature is depletion of follicles with loss of granulosa and thecal cell function
6-7 million oocytes at 20 weeks fetal age
1 million oocytes at birth drop to 400,000 at puberty
300-400 ovulatory events over lifetime
Accelerated follicular loss 2-8 yrs before menopause
Physiology
Granulosa cells produce less inhibin, which provides negative feedback for FSH secretion by the pituitary gland.
Increase in FSH levels After menopause, LH levels are also elevated. Would you check a FSH or LH level to diagnose
menopause?
Symptoms
Menstrual irregularities is the primary reason women seek medical attention
Cycles shorten as increased FSH triggers early ovulation
Skipped cycles due to anovulation
Long periods of anovulation can lead to excessive estrogen states and irregular, unexpected menses
Symptoms
Do you think the perimenopausal women can get pregnant?
– YES
– Guinness World Record = 57 yrs & 120 days
– So, remember to recommend contraception. Low does oral contraceptives may be used in women without contraindications (i.e. smoking).
Symptoms
Hot Flushes– Subjective feeling of intense heat followed by skin
flushing and diaphoresis.
– Sudden dilation of peripheral vasculature secondary to abrupt estrogen withdrawal. Skin temperature increases and core temperature drops.
– Usually, occurs for a few seconds to minutes.
– Duration is about 1-2 years. 25% for > 5 years.
Symptoms
Genitourinary atrophy – A variety of symptoms
– Atrophic vaginitis, urethritis, recurrent UTIs, dyspareunia
– Pelvic organ prolapse is NOT caused by estrogen deficiency
Symptoms
Urinary Incontinence
– Atrophy of estrogen-dependant tissues such as the urethra may contribute to existing causes for urinary incontinence
– Typically addressed with local application of estrogen cream
Symptoms
Sexual Disturbances– Decreased interest in sexual activity
May be related to decreased testosterone levels
May be related to psychosocial stressors
– Anatomic changes secondary to estrogen deficiency Atrophy of vaginal mucosa and lower urethra
Thinning of vaginal mucosa with decreased lubrication and elasticity, leading to dyspareunia
Symptoms
Sleep Disturbances– Estrogen appears related to producing restful, deep-
stage sleep
– Hot flushes more common at night Wakening or disruption of deep-stage sleep
Contributes to feeling of overall fatigue
Symptoms
Mood Swings / Irritability / Depression– NOT associated with menopausal hormone
changes alone
– Stage of life associated with multiple changes (e.g., children leaving home, parents aging, retirement)
– Hot flushes and fatigue can lead to emotional lability
Symptoms
Cognitive Function– Some types of memory and brain function may be
influenced by estrogen
– Some evidence suggests that Alzheimer’s disease is less frequent in estrogen users and the effect was greater with increasing dose and duration of use.
Adverse Health Effects
Cardiovascular Disease– Leading cause of death in US women (f/b
malignancies, cerebrovascular disease and MVAs)– Death rate for CV disease is 3X the rate for breast
cancer and lung cancer.– Changes in lipid profile in menopause
Increased LDL Decreased HDL ? Decrease in triglycerides
Adverse Health Effects
Osteoporosis
– Spinal bone density peaks at 20 years, while cortical bone density peaks in late 20s
– Rate of loss of 0.5%/year prior to age 40, then anywhere from 2-9%/year for first 10-15 years after menopause
– Primary loss is trabecular bone, leading to compression fractures, loss of height, kyphosis
Adverse Health Effects
Osteoporosis– Osteopenia = BMD between -1 and -2.5 SD of a young, white
adult woman.
– Osteoporosis = BMD -2.5 or greater SD
– 25-50% of women will have spinal compression fractures by age 70
– 20% of Caucasian women age 80 will have hip fractures, with 15-20% mortality.
– Annual incidence is 1.3% after age 65
Adverse Health Effects
Osteoporosis– High risk:
Caucasian, Asian Thin, inactive, smokers High caffeine/alcohol intake, low dietary calcium, high dietary
protein and phosphates H/o oligomenorrhea, excessive exercise, eating disorder Medical conditions – hyperthyroid, cancer, myeloproliferative
disorders
– Low Risk: African American Obese, active
Adverse Health Effects
Osteoporosis– Protection:
Ca supplements (1200mg, 1500mg) Weight-bearing exercise HRT: estrogen increases
– Intestinal calcium absorption– Renal conservation of calcium– Increases 1,25-dihydroxyvitamin D (active form)
Vitamin D (400-800IU)
Hormone Replacement
Types of hormone replacement– Estrogen alone (for women without a uterus)– Estrogen and progesterone
Sequential Continuous
– Local estrogen– SERM’s (Selective Estrogen Receptor Modulators)
HRT - Advantages
1. Relief of vasomotor symptomsHRT is effective in reduces the number of hot
flashes
6-8 weeks to see maximal effect
Combination HRT (0.625mg estrogen/2.5mg MPA)
What about lower doses of HRT?– For combination HRT, all doses resulted in similar relief of
symptoms
– For estrogen alone, most relief with higher doses
HRT - Advantages
2. Vaginal atrophy
– Menopause thins the vaginal epithelium and increases the vaginal pH (> 6.0).
– Estrogen decreases the vaginal pH, thickens the vaginal epithelium and reverses vaginal atrophy.
– Less atrophic changes with higher doses of HRT
HRT - Advantages
3. Bone protection
Reduction of bone loss
Prevents OP-related hip fractures
Protects the spine and the small bones
WHI: 5 fewer hip fractures per 10,000 person-yrs
HRT - Advantages
4. Colon cancer
– Some observational studies have suggested a reduced risk.
– WHI: 6 fewer cases / 10,000 person-yrs
HRT - Disadvantages
1. Endometrial cancer
8-10 fold increased risk with unopposed estrogen.
PEPI: unopposed estrogen x 3 yrs = 24% with atypical hyperplasia (vs 1% women on placebo)
Risk is increased with: – Increased duration and dose– Continuous versus cyclic therapy– Absence of a progestin
HRT - Disadvantages
2. Breast cancer
– Meta-analysis of 51 case-controlled & cohort studies showed no increased risk with short-term use.
– After 5 years of use, risk increased by 35%.
– WHI: 8 more invasive cases / 10,000 person-yrs
– Women diagnosed with breast cancer while using HRT have been shown to have better survival
HRT - Disadvantages
3. Thromboembolic disease
– Increases risk for DVT 2 – 3.5 fold
– Strokes: 8 more / 10,000 person-yrs
– PEs: 8 more / 10,000 person-yrs
HRT - Disadvantages
4. Cardiovascular disease:– Traditionally, HRT was thought to provide
protection against coronary heart disease (CHD)– Observational studies found lower rates of CHD in
postmenopausal women on HRT. – The consensus was that CHD was about 35-50%
lower in women using HRT.– Many studies showed that HRT improved lipid
profiles.
HRT - Disadvantages
4. Cardiovascular disease:– What about secondary prevention? i.e. women who
have a h/o coronary heart disease, does HRT help?
– Heart and Estrogen/Progestin Replacement Study (HERS) was a RCT, double-blinded study of 2,763 PM women with intact uteri and a h/o CHD
– 52% higher rate of major coronary events in the 1st year
– Then there was a reduction in the risk with longer use – i.e. 33% lower risk in the 4th and 5th years
HRT - Disadvantages
4. Cardiovascular disease:– What about primary prevention? i.e. in healthy
women, does HRT prevent CHD?
– Women’s Health Initiative (WHI)
– RCT of 16,608 postmenopausal women aged 50-79 years old with an intact uterus
– 40 different US centers
– Combination HRT – 0.625mg CEE and MPA 2.5mg vs placebo
HRT - Disadvantages
4. Cardiovascular disease (WHI):– 7 more CHD events– 8 more strokes– 8 more PEs– 8 more invasive cancers
– Study stopped after 5.2 yrs (planned 8.5yrs) because of cases of breast cancer
SERMs
Selective estrogen receptor modulators
Work as agonists and antagonists depending on the tissue
Raloxifene and tamoxifen
SERMs
Estrogen Raloxifene TamoxifenPrevent OP ↑ ↑ ↑ ↑ ↑ ↑
Risk Breast ↑ ↑ ↓ ↓ ↓ ↓Cancer
Hot Flashes ↓ ↓ ↓ ↑ ↑
Endometrial ↑ ↑ no effect ↑ Cancer
Venous ↑ ↑ ↑ ↑ ↑ ↑ Thrombosis
SERMs
Overall, SERMs can help to prevent OP and breast cancer
However, they aggravate hot flashes, the most common indication for estrogen therapy.
Also, tamoxifen stimulates the endometrium.
Alternative Medicine
Limited studies with relatively short duration of therapy and follow-up.
Soy and isoflavones may be helpful in the short-term (< 2 yrs) for vasomotor sx and may protect against osteoporosis.
35-75mg qd isoflavones / day
Black cohosh may be helpful in the short-term (< 6 mos) for vasomotor symptoms.
Summary
Health Risks– Osteoporosis– Lipid abnormalities– Cardiovascular disease– Cancer
Summary
Menopause is the natural course aging of the female reproductive system, driven by loss of oocytes
Symptoms of menopause include:– Menstrual irregularities– Hot flushes– Sleep disturbances– Mood changes– Sexual disturbances– Urinary incontinence– Cognitive function– Hair growth
Hormone Replacement
Benefits Detriments
Vasomotor sx
Vaginal atrophy
Osteoporosis
Colon cancer
Endometrial ca
Breast ca
VTE
CHD
Abnormal Bleeding
A 44-year old woman presents for evaluation of abnormal menstrual bleeding. Her periods have been regular in the past but for the last 6 months she has had a period every 35-56 days, lasting 7-9 days. The bleeding is heavier than usual and she feels tired all the time. She has gained 15 lbs over the last 2 years, which she believes is due to lack of exercise and increased eating/sleeping. She complains that her skin is dry. Exam is unremarkable. What would your recommend next?
– Check pregnancy test– Discuss exercise / eating patterns– Check TSH, PRL– Consider endometrial biopsy– Expectant management versus hormonal management
Health Maintenance
58 year old postmenopausal woman referred to you by a friend. She has no known medical problems and is on no medications. Her social history is remarkable for an 80-pack/year history of tobacco use. Her physical exam is unremarkable. What are the important health maintenance aspects of the exam to focus on?
– Blood pressure– Pelvic exam– Breast exam / mammography– Fecal occult blood– Smoking cessation– Flu shot– Osteoporosis
Abnormal Bleeding
A 47 year old woman, G2P2, presents with menstrual cycles varying in length from 20 to 40 days. Until 9 months ago she had regular 28 day cycles. She reports frequent hot flushes. She recently resumed sexual activity and uses no contraception, but she does not desire pregnancy. She does not smoke and has no other medical problems. Her physical exam is unremarkable. What are her options for cycle control?
– Low dose combination oral contraceptive– Continuous low dose estrogen and progestin menopause regimen– Cyclic progestin therapy for 12 days a month– Continuous low dose estrogen (0.625mg conj EE)– Estradiol vaginal ring
Osteoporosis
A menopausal patient with osteoporosis has been reading information on the Internet about different treatment modalities for osteoporosis. She wishes to know more about what therapies are actually available and how they work?
– Estrogen: Reduces osteoclast activity– SERMs: Reduces osteoclast activity– Bisphosphonates: Reduces osteoclast activity
Take on empty stomach, first thing in AM with 8oz water and no food for 30 minutes
Take sitting up due to esophagitis risk Calcium supplementation within 4 hours
– Calcium / Vitamin D supplements