Menopause Overview Menopause is a natural part of a woman's life cycle. monthly periods end. freedom from pregnancy and additional child- raising responsibilities.
Effects of Menopause Vasomotor instability- hot flashes, and waking during the night Mood changes -Mood swings; depression or anxiety Cognitive function- decreased verbal memory Sexual function - libido Urogenital - dryness, itching, pain during sexual intercourse sudden or frequent urinating
Menopause Increases Women's Risk for Osteoporosis women can lose up to 5 percent of their bone mass per year in the first 5 years following menopause.
Risk of Cardiovascular Disease Also Increases after Menopause The risk of CVD increases in women after menopause By age 60 heart disease becomes as common in women as in men.
Managing Menopause Healthy lifestyle to protect against osteoporosis and cardiovascular disease Maximize medications for these conditions A balanced diet, calcium and vitamin D; Weight reduction if overweight; Stop smoking; Weight-bearing exercise Yearly mammogram and breast examination
Treating the Symptoms of Early Menopause: Individual counseling or support groups Vaginal moisturizers such as Vagisil or Replens. Lubricants, such as K-Y Jelly or Astroglide Low-dose vaginal estrogen Lack of desire may be helped with more open communication with your partner. Creating a pleasurable atmosphere at home and making a point to enjoy other activities with your partner.
Treating the Symptoms of Early Menopause with Non-Hormones: Selective-Serotonin Reuptake Inhibitor (SSRI) drugs and Serotonin Norephinephrine Reuptake Inhibitor (SNRI) drugs. Gabapentin Medroxyprogesterone acetate and megestrol acetate, progesterone-type drugs. Clonidine
Changing Aspects of Hormone Replacement Therapy Conventional rationale for HRT derived from favorable outcomes of observational studies in perimenopausal women Recent randomized clinical trials showed potentially adverse effects of HRT in late postmenopausal women RCTs results have discouraged HRT use in perimenopausal women
Benefits of HRT Relief of menopausal symptoms Increase bone density CVD benefit ? Improve memory? Improve sexual function? Youthful look? Decrease colon cancer Decrease macular degeneration
Women's Health Initiative 2002 The largest randomized prospective trial evaluating the effects of estrogen plus progestin and estrogen alone versus placebo (no hormone).
WOMENS HEALTH INITIATIVE CLINICAL TRIAL ( WHI – US ) OBSERVATIONAL, CLINICAL CORHORT 150,00 POSTMENOPAUSAL WOMEN GRP ,000 WOMEN Objective : To evaluate the efficiency of Low Fat diet in the prevention of breast, colorectal cancer and coronary heart disease. GRP ,000 WOMEN Objective : To evaluate the effect of Calcium &Vitamin D in fractures and colorectal cancer. GRP ,500 WOMEN Objective : To assess HRTs efficacy in the prevention of cardiovascular diseases and fractures.
Estrogen in Osteoporosis Prevention of bone loss and fragility fracture WHI – 33% reduction in fracture ratethe only therapy with efficacy data on prevention of fracture in women with osteopenia
Alternate Treatments Are Available Non-hormonal treatments to prevent and treat osteoporosis bisphosphonates, elective estrogen receptor modulators (SERMs), parathyroid hormone (PTH) calcitonin.
HRT and Risk of Cardiovascular Disease The increase in risk following menopause suggests that estrogen made by the ovary prior to menopause may protect against heart disease. However, recent studies have shown no benefit to the use of postmenopausal hormone therapy in heart disease prevention and indicate the need to use other modalities to help women fight heart disease.
HERS II Results from extended, open-label evaluation of the HERS (Heart Estrogen/progestin Replacement Study) indicate no cardiovascular benefit of HT in postmenopausal women with previous history of cardiovascular disease JAMA 2002
WHI and CVD risk Estrogen + Progestin increased CVD by 29% Estrogen only in hysterectomized no increase in CVD risk
Estrogen+Progestin Therapy and Risk of CHD: Results According to Time Since Menopause Womens Health Initiative – E+P trial Women <10 years since menopause: RR=0.89 Women yrs since menopause: RR=1.22 Women 20+ years since menopause: RR=1.71 (But no modifying effect of age) Manson JR et al NEJM 2003
Reducing Risk of CVD Statins have been shown to lower the risk of CVD in individuals with abnormal circulating lipids and those who have a family history of heart disease. Small doses of aspirin daily
HRT and cognitive function WHI Memory Study (WHIMS) Women aged 65 or older who took estrogen plus progestin had twice the rate of dementia, including Alzheimers disease, as those taking placebo. Estrogen plus progestin did not protect against mild cognitive impairment (e.g., trouble paying attention and remembering). JAMA 2003
Cognitive function The Women's Health Initiative data suggest that women who initiate hormone therapy at age 65 or older have worsening dementia than women who take no hormones. Until more is known, hormone therapy cannot be recommended for prevention of Alzheimer's disease.
Other Benefits Taking estrogen plus progestin lowers the risk of developing colon cancer by 37% Taking estrogen lowers the risk of developing age-related macular degeneration, a degeneration of the retina of the eye.
Risks of HRT Stroke WHI 39% increased in E 41% increased in E+P Breast cancer WHI no significant increase in E 26% increased in E+P Venous thromboembolism 47%
Discordance between observational and randomized studies: different populations StudiesObservationalRandomized Characteristics Healthier, less comorbidities, leaner, less smokers Less healthier, more comorbidities, fatter, more smokers Age at start of HRT Typically 35 to 55 years Typically >60 years HERS: 66.7 years ERA: 65.8 years WHI: 63.2 years Time since menopause Peri- or early postmenopausal Late menopause HERS: 17.7 years ERA: 15.8 years WHI: 18.0 years Adapted from Karas RH. Clin Obstet Gynecol 2005;47:489.
"Designer Estrogens" Selective Estrogen Receptor Modulators (SERMs). Act as beneficially as estrogen on some tissues and as estrogen-blockers on other tissues Tamoxifen-used to prevent breast cancer Raloxifene - used to prevent osteoporosis, Selective estrogen tissue Tibolone
Commonly Used Alternatives to Hormone Replacement Therapy Black Cohash- Camomile-Chasteberry- Dong Quai- Ginseng- Licorice Root- St. John's Wort- Valerian- Soy Products
Testosterone/DHEA Supplement in Women Not approved Variable to no benefit Data shows benefit in hypopituirarism, premature ovarian failure, bilateral oophorectomy and primary adrenal insufficiency
Conclusion 1 Short-term hormone therapy is approved by the U.S. Food and Drug Administration in younger women for some symptoms of menopause, including hot flashes, vaginal dryness and painful intercourse the lowest effective dose possible. the lowest effective dose possible. Individualized and time dependent
WHAT IS ANDROPAUSE? (Late Onset Hypogonadism) [PADAM / ADAM] A clinical condition characterized by a partial deficiency of androgens in blood and/or decreased testosterone availability to various systems or organ functions.
Typical appearance of testosterone deficiency Clinical Symptomatology Usual appearance of young men
Recent Insights into the Andropause Low testosterone levels affect mood, vitality, sexuality brain: decreased libido depressed mood heart: increase in cardiovascular risk muscle: decrease in strength & mass kidney: anemia due to < erythropietin production bone: decreased bone mineral density sexual organs: erectile dysfunction
Pathophysiology Testosterone decreases with aging SHBG increases with aging with a decrease in bioavailable testosterone Decline in testicular Leydig cells Due to abnormal hypothalamic –pituitary- testicular axis
Testosterone Replacement: Is it necessary? IMPROVEMENT OF SXS OF ANDROPAUSE BPH AND PROSTATE CANCER RISK CV EVENTS, ETC
Expectations from testosterone treatment Bone density Lean body mass / muscles Erythropoesis Physical activity Mental activity Mood Cognitive abilities Libido Quality of life
Osteoporosis Not just a female disease! 25–30% of hip fractures occur in men! Serious ! 25% die of it in the short term 25% die of it in the longer term Only 20% return to their former quality of life; many more need assistance 51 % suffer from depression (Cowith activities of daily living olsaet, Aging Male congress 2002) Gooren L Lecture Int. Symposium of Andropause Society, London, 2003
Amory JK et al. J Clin Endocrinol Metab 89(2): (2004) Bone Mineral Density (Lumbar Spine) after 36 Months of Testosterone Treatment in 70 Elderly Men (mean age 71, T<350 ng/dL) * * * * p<0.05 * *
Body Composition, Strength and Function Role of testosterone Increases nitrogen retention Increases protein synthesis Bhasin (NEJM, 1996) TRT dose related increase in skeletal muscle mass and strength In a systematic review of 6 trials T reduced fat mass and increased lean body mass
Testosterone Improves Physical Performance in 70 Elderly Men (mean age 71, T<350 ng/dL) Page ST et al. J Clin Endocrinol Metab 90(3): (2005) leftright * * * * * * * *p<0.05
TRT and Depression Margolese, HC, J Geriatr Psychiatry Neurol 2000; 13: Testosterone decreases with advancing age in males Lower bio-T in depressed aging males Testosterone deficiency and depression symptoms overlap, current treatments are often insufficient for depression The use of testosterone for depressed hypogonadal males (with documented low Bio- T) holds promise
Sexual Function Jain Meta-analysis (J Urol, 2000) TRT 57% overall improvement rate for ED TRT improved nocturnal erection and penile rigidity in hypogonadal males (Cunningham 1990, J Clin Endoc Metab; Arver, 1996 J Urol) TRT –direct vascular effect on the corpora cavernosa mediating nitric oxide effects (Aversa 2003, Clin Endocrin) TRT potentiates libido by a central effect and erection by central and peripheral effects
TRT and CV Old dogma: T is a risk factor for cardiac disease Men have both high incidence of CV and higher T levels than women But: Little data support a causal relationship between higher T levels and heart disease. (Rhoden & Morgentaler 2004)
Hematopoietic Effects of TRT Red Blood Cells T stimulates erythropoietin secretion by the kidneys and bone marrow RBC precursors
Indications for testosterone substitution Symptoms of hypogonadism and morning testosterone levels below 12 nmol / l Absolute contraindications for testosterone substitution Prostate carcinoma Desired paternity (for secondary hypogonadism, gonadotropin administration is required) Relative contraindications for testosterone substitution Benign prostate hyperplasia, sleep apnea, polycythemia, criminal sexual behavior Nieschlag and Behre, Andrology, 2000, Springer
Conclusion 2 Late Onset Hypogonadism can lead to dysfunction of multiple organ systems and detriment of the quality of life of the aging male Diagnosis can be made by clinical and biochemical parameters Testosterone replacement is indicated in carefully selected patients and leads to improvement of symptoms
Can Growth Hormone Prevent Aging? NEJM Volume 348: NEJM Volume 348: February 27, 2003 Number 9NextFebruary 27, 2003Next Mary Lee Vance, M.D.
The Bottom Line on growth hormone Although growth hormone levels decline with age, it has not been proven that trying to maintain the levels that exist in young persons is beneficial. Considering the high cost, significant side effects, and lack of proven effectiveness, HGH shots appear to be a very poor investment. So called "growth-hormone releasers," oral "growth hormone," and "homeopathic HGH" products are fakes.
Summary Menopause and Andropause are characterized by decreasing sex hormones and clinical features that go with it. Hormone replacement in men and women has benefits and risks. Hormone replacement should be used in the perspective of current available data.
In the autumn years of life, a woman or a man deserves an Indian summer rather than a winter of discontent. by : Robert Greenblatt