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32 Cards in this Set
- Front
- Back
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Menopause
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•Significant life event for women
–somatic changes –physiological changes –psychological changes •Literally means “end of monthly cycles” –Healthy women spend 1/2 to 1/3 of their lives in menopause •Characteristic symptoms –hot flashes –night sweats –vaginal dryness –dyspareunia (painful intercourse) |
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Definitions of Menopause
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•perimenopause: time between menstrual irregularity and menopause
•natural menopause: no spontaneous menstrual period (amenorrhea) for 12 consecutive months with no other pathologic or physiologic cause •premature menopause: menopause onset prior to 40 years of age •induced menopause: cessation of menses following hysterectomy with or without bilateral oophorectomy |
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Estrogen, Progesterone, & Testosterone in Women
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•Estrogen
-almost all testosterone is converted to estrogen before leaving the ovaries –promotes development of secondary sex characteristics –regulation of menstrual cycle –3 existing types •17-estradiol-potent (most abundant) •Estrone-potent •Estriol-impotent (converted from 17-estradiol & Estriol in the liver; liver impairment ->increase estrogen activity) •Progesterone –regulation of menstrual cycle, pregnancy, and embryogenesis -liver degrades progesterone •Testosterone –precursor to estrogen synthesis –promotes sexual functioning |
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Endocrine Changes
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•Decreased production of inhibin
–increased FSH –increased LH •Loss of oocytes & ovarian follicles –altered estrogens –decreased testosterone –decreases follicular response |
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Structural & Physiological Changes
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•Ovaries shrink
•Genitourinary tract changes •Breasts become smaller •Endometrium becomes thinner •Mild hirsutism & other androgenic effects |
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Signs & Symptoms
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Vasomotor
•hot flashes -?GnRH release affecting adjacent temperature-regulating area in the brain - •night sweats •felt in face, neck, & upper trunk •frequency & severity can vary depending on: –race/ethnicity –menstrual status (peri- vs post-menopausal) –body mass index (BMI) –physical activity –smoking status Genitourinary •fluctuating hormone levels –irregular uterine bleeding –eventual amenorrhea •atrophy of urogenital epithelium •vulvovaginal atrophy –vaginal dryness –dyspareunia –increased UTIs •loss of uterine support –incontinence |
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Changes with Menopause
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•Osteoporosis
-increase bone resorption •Coronary artery disease (CAD) -altered lipid metabolism: increase LDL, decrease HDL -increase artherosclerosis •Fatigue •Mood changes –depression –anxiety –irritability •Sexual dysfunction •Memory loss & impaired concentration •Insomnia |
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Treatments
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•Estrogens
–HRT for urogenital atrophy •Progestins •Combination estrogens + progestins •Androgens •Non-hormonal •Nutraceutical/herbal options |
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Side Effects of Estrogens
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•Breast tenderness, bloating, nausea
•Migraine headaches •Cholecystitis •Endometrial cancer •Breast cancer •Stroke •PE, DVT |
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HRT for Urogenital Atrophy
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•Effective for vaginal dryness, dyspareunia, incontinence
•Topical estrogen creams & gels –use daily for 1-2 weeks –followed by ½ dose daily for 2 more weeks –then maintenance doses 1-3 times per week •Intravaginal estrogen rings –Inserted once every 3 months •Intravaginal estrogen tablets –inserted daily for 2 weeks, then twice weekly |
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Treaments: Progestins
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•Decreases risk of endometrial cancer & hyperplasia
-not indicated for low dose loacalised admin •Decreases risk of estrogen-induced irregular bleeding •May or may not help in the prevention of osteoporosis •Administered cyclically or continuously -Medroxyprogesterone acetate: most common -Micronized or natural progesterone: appears less likely to cause mood changes |
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Side Effects of Progestins
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•Menstrual symptoms
-breast tenderness, bloating, edema, anxiety, and depression •Limited bleeding •Weight gain •Headache •Drowsiness •Altered cholesterol levels –decreased HDL –increased LDL -Increase BP by causing sodium and water retention |
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HERS & HERS2
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•Increased rates of venous thromboembolism and biliary tract surgery in older women with CHD on HT
•No overall effect of HT on cardiovascular disease (CVD) event rates |
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Effects of Women’s HRT on MI & Stroke
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-Estrogen alone has decrease CHD, but not recommended for primary
-initiation of HT in early postmenopausal women (less than 5 years) is not likely to increase cardiovascular risk. However, risk increases when starting HT 10 or more years beyond menopause. -Not recommeded to primary/secondary strokes |
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Effects of Women’s HRT on Cancer Risks
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Breast Ca
•Increased risk for breast Ca: >5 yrs of HT •Avoid HT in women with a history of breast cancer • Ovarian cancer -Increased risk with HT • Endometrial cancer -Increased risk with unopposed estrogen • Colorectal cancer -Possible decreased risk with HT |
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Effects of Women’s HRT on Venous Thromboembolism (VTE)
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• Greater risk with increasing age, obesity, factor V Leiden mutations,
smoking • Avoid HT in women with active or a history of deep venous thrombosis (DVT) or pulmonary embolism (PE) |
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Effects of Women’s HRT
on Cognition & Dementia |
• Reduced risk of dementia with long-term
estrogen use seen in observational studies • HRT is NOT recommended for treatment or prevention of dementia |
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Effects of Women’s HRT
on Urinary Incontinence |
Increased risk of urinary incontinence with estrogen plus
progestin therapy • 3 times more likely to develop urge incontinence • 5 times more likely to have stress incontinence |
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Effects of Women’s HRT on Osteoporosis
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• Estrogen can reduce rate of osteoporosis
– prevent hip fractures – prevent vertebral fractures – prevent other osteoporotic fractures • Should not be used solely for prevention of osteoporosis in postmenopausal women – safer & more effective agents are available |
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Effect of Women’s HRT on Gallbladder Disease
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• Estrogen +/- progestin increases the risk
of biliary tract disease – Gall bladder procedures (predominantly cholecystectomies) • Estrogen is thought to promote gallstone formation & cholecystitis • Progestin does not seem to influence this effect |
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Contraindications & Precautions
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Contraindications
• unexplained vaginal bleeding • active liver disease or chronic impaired liver function • active or history of DVT or PE • active or recent (within past yr) arterial thromboembolic disease – stroke, MI • known, suspected, or history of breast cancer • endometrial carcinoma • untreated hypertension -unknow or suspect edestrogen-dependent neoplasm Monitoring • at least annually • blood pressure • breast exam & mammogram • bone densitometry • endometrial hyperplasia • vision changes • new or worsening migraines • thromboembolic disorders • lipid profiles |
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Treatment: Non-Hormonal
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instability of serotonin and norepinephrine in the hypothalamus
SSRIs -Fluoxetine 10-30mg daily -Paroxetine 10-37.5mg daily (highest effinity for NA receptors) Others -Clonidine 0.1-1.5mg daily (not for normotensive pts) -Transdermal Clonidine -Gabapentin 900-2700mg SNRI -Venlafaxine 37.5-75mg daily • Non-pharmacologic management of hot flashes – avoid caffeine, alcohol, & spicy foods – adjust room temperature & dress in layers – maintain a normal body weight – smoking cessation – regular exercise -maybe vitamin E |
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Treatment: Nutraceutical/Herbal Options
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• No clinically important effects on hot flashes
-black cohosh -red clover Soy & soy extracts - phytoestrogen -not recommend in current or hx of breast ca |
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Options & Alternatives to HRT for Menopause-Related Conditions
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• Cardiovascular diseases
• Aspirin • Lipid-lowering agents • Antihypertensive agents • Vaginal symptoms • Nonhormonal lubricants, moisturizers, oils • Vasomotor symptoms • SSRIs • SNRIs • Clonidine • Gabapentin • Black cohosh • Soy isoflavones • Osteoporosis • Calcium and vitamin D • Bisphosphonates • Calcitonin salmon • Teriparatide • SERMs :Does not increase risk of breast cancer |
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Summary of Women’s HRT
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• Short-term therapy should still be considered,
although careful consideration of the risks & benefits should be observed • HRT should NOT be offered for prevention of chronic diseases • HRT should NOT be recommended to women with a high risk of CV disease • Long-term treatment is associated with an increase incidence of breast cancer • All women should be counseled on the risks, benefits, & uncertainties of HRT Elderly that are on HRT for long time should consider ceasing as increase risk of CVD/cancer |
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Andropause
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• As men age, their serum concentrations of
testosterone and, to a greater extent, free testosterone, decrease • Decline is sometimes referred to as "andropause" or "late-onset hypogonadism“ |
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Clinical Consequences
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No consequence are known but symptoms do parallel with aging & hypogonadism
– Sexual dysfunction – Decreased BMD – Muscle mass decline, increase in adipose – Decreased muscle strength – Decreased cognition – Metabolic changes |
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Testosterone Recommendations – The Endocrine Society
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-no pituitary/testicular disease
-testosteron <200ng/dl or 6.9nmol/l -clinically symptoms of androgen insufficiency |
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Transdermal Testosterone
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Gel
– Wash hands thoroughly after application – Avoid skin contact until the gel has dried – Keep the application site covered |
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Adverse Effects of Testosterone Therapy
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• Pain at injection site (IM preparations)
• Contact dermatitis (patch >> gel) • Acne or oily skin • Gynecomastia • Aggressive behavior (adolescents) • Short stature (adolescents) • Increased prostate volume/PSA • Urinary retention (BPH exacerbation) • Sleep apnea • Erythrocytosis (high haematocrit) |
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Testosterone Tx: Potential Harm?
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Prostate Ca
-longer trials needed to rule out -may increase PSA BPH -May worsen BPH but meta-analysis says no significant worsen Erythrocytosis -esp. w/long acting testosterone esters -4x more likely to have hematocrit >50% -monitor hematocrit at baseline, 3, 6 months. -if high rule out other cause, if still high stop/reduce dose of testosterone -High haematocrit males has greater mortality & CV mortality |
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Contraindications to Testosterone Therapy
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• Very high risk of adverse outcomes
– Prostate cancer – Breast cancer • High risk of adverse outcomes – Undiagnosed prostate nodule – Unexplained PSA elevation – BPH with severe urinary retention – Erythrocytosis – NYHA Class III or IV heart failure |
