Advancing Age And Menopause ppt

Menopause and Reproductive Aging

• Menopause: Permanent cessation of menstruation due to ovarian follicular failure; occurs around age 51.4 (median), range 48-55 years. Perimenopause, the transitional phase, typically lasts 4 years, beginning around age 47.5.
• Climacteric: The physiologic period of ovarian function decline.
• Primary Ovarian Insufficiency: Cessation of menstruation due to ovarian follicle depletion before age 40.
• Factors Associated with Earlier Menopause: Surgical causes (30%), family history, smoking, (possible) blindness, abnormal karyotype, precocious puberty, and left-handedness.
• Factors Associated with Later Menopause: Obesity, higher socioeconomic status.
• Menopause in Different Populations: In many underdeveloped countries, lifespans are shorter, limiting the experience of menopause. In developed nations, most people live beyond menopause. This is due to lower birth rates and longer lifespans.
• Types of Menopause: Physiologic, iatrogenic (surgical, radiation, chemo), autoimmune ovarian tissue destruction, and infections/tumors (rare).
• Reproductive Aging: At birth, a woman has about 1 million follicles; only approximately 1,000 remain by menopause. Most follicular loss is due to atresia (follicle death) rather than ovulation. Atresia accelerates around age 37.

Perimenopause

• Ovarian Function in Perimenopause: Ovaries decrease in size; estradiol production declines, with estrone becoming more significant; follicle numbers decrease; inhibin production decreases (which normally suppresses FSH; reduced follicle response to FSH/LH leads to irregular ovulation).
• Perimenopause Contraception: Women still need contraception.
• Inhibin: A hormone produced in the gonads, pituitary, placenta, corpus luteum, and other organs. It inhibits FSH and LH. Follicle aging results in less inhibin production, leading to FSH and LH elevations (predictive of reduced fertility).
• Fertility Decline: Fertility begins to decline around ages 35-37, before perimenopausal signs are evident. Natural pregnancy is still possible until menopause.
• Day 3 FSH Testing: A method for assessing ovarian reserve. Elevated Day 3 FSH indicates reduced ovarian reserve (fewer eggs, reduced quality). Normal Day 3 FSH (<9) doesn't guarantee good ovarian reserve/quality.
• Perimenopause Length: Typically +/- 3 years from the defined menopause. Characterized by shortening of menstrual cycles, or anovulatory/prolonged cycles in duration, and a shorter follicular phase.

Menopause and Hormone Levels

• Serum Hormone Levels at Menopause: Circulating estrogens, the ratio of estrogen to androgen, sex hormone-binding globulin (SHBG), peripheral aromatization of DHEA to estrone, E2: E1 ratio, circulating bioavailable testosterone all decrease.
• Menopausal Hormone Levels (FSH, LH, Estradiol): FSH and LH levels generally increase, and estradiol levels sharply decrease. Testosterone levels decrease slightly, making it relatively more prevalent post-menopause.
• Estrogen Level Testing: Estrogen levels widely fluctuate during reproductive years, making it unreliable for predicting fertility. Specific ranges for mid-follicular, periovulatory, and mid-luteal phases are provided, with postmenopausal levels being 0-40 pg/mL.
• Diagnosis of Menopause: Determining menopause is primarily achieved through increased FSH levels.

Menopause Symptoms and Manifestations

• Menopause Affects Androgen Levels: Bioavailable 5-DHT increases leading to defeminization, hirsutism, and mild virilism.
• Estrogen Changes During Menopause: In premenopausal women, estradiol (E2) is the primary estrogen, produced by the ovary. In postmenopausal women, estrone (E1) is primarily generated by peripheral conversion of Androstenedione.
• Target Organs Affected by Estrogen: Cardiovascular, urogenital, bone, skin/teeth, and brain.
• Symptoms of Estrogen Deficiency: Vasomotor instability, altered menstrual function, vaginal atrophy (dryness, discomfort, dyspareunia, bleeding), urinary tract symptoms (incontinence/pain), osteoporosis.
• Hot Flashes: Temporary increases in skin temperature, vasodilation, blood flow, skin conductance, and heart rate followed by a drop and sweating.
• Hot Flash Onset: 10% prior to menopause, 50% after cessation of menses.
• Cardiovascular Changes: Increased risk of CVD (leading cause of death in US women); cholesterol increases, triglycerides and LDL increase, HDL decreases near/after menopause.
• Genitourinary Symptoms of Menopause: Vaginal and urethral atrophy, reduced urethral closure pressure (increasing incontinence), urinary tract prolapse, urethritis and cystitis, increased urgency/frequency/dysuria/nocturia.
• Menopause & Osteoporosis: Accelerated bone loss (1-2% per year), mainly trabecular bone initially, then cortical bone. Risk factors include low BMI, early menopause, family history, low calcium/vitamin D intake, high caffeine/alcohol/protein intake, and smoking.
• Skin and Teeth Changes: Decreased epidermal thickness, collagen content, and slowed healing postmenopausally. Postmenopausal estrogen therapy preserves collagen and reduces skin thinning.
• Neurologic Symptoms: Anxiety, depression, irritability, fatigue, headaches, sleep difficulties, inability to concentrate.

Menopause Treatment

• Hormone Replacement Therapy (HRT): Oral treatment with low-dose estrogen +/- progesterone (depending on uterine status). Methods (examples provided) include lowering doses, vaginal or transdermal routes.
• HRT Indications: Moderate-severe vasomotor symptoms (hot flashes), vulvar/vaginal atrophy (GUSM), and osteoporosis prevention.
• HRT Contraindications: History of breast cancer, CVD, VTE, stroke, active liver disease, unexplained bleeding, or high-risk endometrial cancer.
• HRT Potential Side Effects: Headaches, breast pain/tenderness, vaginal bleeding, nausea, mood changes, leg cramps, rash, itching, diarrhea.
• Hormone Replacement Patches: Available as estrogen-only and estrogen + progesterone; observational studies suggest that transdermal routes may have lower risk of VTE.
• Bioidentical Hormone Replacement Therapy (BHRT): Uses plant-derived hormones; poses similar risks/benefits and side effects for conventional HRT. FDA does not consider it safer.
• Intravaginal Estrogen Therapy: For urogenital symptoms (GUSM only); does not treat hot flashes. Potential side effects include abnormal bleeding, breast pain and nausea.
• Intravaginal DHEA Insert (Intrarosa): For vaginal dryness/dyspareunia; potential side effects include discharge and abnormal Pap smear.
• Why Concern about HRT? Women's Health Initiative (WHI) study—stopping early due to increased CVD/breast cancer risks with combined estrogen-progesterone therapy. WHI found mixed results (benefits/risks) of estrogen-only therapy.
• Breast Cancer Risk & HRT: HRT is a weak risk factor but still needs consideration. Breast cancer risk in general increases over time.
• Alternatives to HRT: Dietary/lifestyle changes.
• Other Hot Flash Treatments: SSRIs and SNRIs (paroxetine approved FDA for hot flashes). Options for those who don't want or can't take HRT.
• Non-Hormonal GUSM Treatments: Lifestyle changes, vaginal lubricants/moisturizers, microablative CO2 laser.
• Osteoporosis Treatments: Bisphosphonates (decrease osteoclast activity); concerns about digestive irritation (take on empty stomach, with water, and remain upright).