Transcript Menopause
Menopause Gyne I 1. Menopause is the period in which a permanent cessation of menses occurs because of loss of ovarian activity. 2. Menses usually stop between 50 and 52 years of age; the median age of menopause is 51.3 years, with a range of 41 to 55 years. 3. Premature menopause is defined as the permanent cessation of menses occurring before 40 years of age. Peri-menopause 1. The perimenopause refers to the period just before and after the menopause, usually ranging from 40 to 55 years of age. 2. The transition is a term used to describe the years leading up to and preceding the menopause. a. This period is marked by menstrual cycle irregularity b. The median age of onset of menstrual irregularity is 47.5 years; the transition lasts an average of 4 years. c. Ten percent of women abruptly stop menstruating without preceding cycle irregularity. Climacteric 1. Climacteric is a broad term encompassing the transitional years, the menopause, and the postmenopausal years. 2. This period reflects the decline and loss of ovarian function and the long-term consequences of reduced estrogen levels. PHYSIOLOGY OF THE PERIMENOPAUSE Ovarian function.. 1. The number of remaining follicles is reduced and those remaining are less sensitive to gonadotropin stimulation 2. Follicular function varies from cycle to cycle within the same individual. 3. As follicular maturation declines, ovulation becomes less frequent as the menopause approaches. Although fertility rates are markedly reduced, conception can occur during this time of fluctuating ovarian activity. Endocrinology 1. Inhibin production by the ovary is reduced. Inhibin exerts a negative feedback on the secretion of follicle-stimulating hormone (FSH) by the pituitary. 2. An increase in FSH levels 3. Luteinizing hormone (LH) secretion escapes the negative feedback of inhibin, LH levels rise much later in the transition than FSH levels 4. Estradiol levels fluctuate but remain within normal until follicular development stops completely. 5. Progesterone levels fluctuate depending on the presence and adequacy of ovulation and are frequently low during the transition. 6. Androgen levels steadily decline during the transition period. Menstrual cycles Changes in the menstrual cycle reflect changes in ovarian function 1. Changes in menstrual cycle regularity occur as a woman progresses through her forties. Cycle length is determined by the length of the follicular phase. It is variable and may be normal, shortened, or prolonged. 2. Shortening of cycle length occurs early in the transition and is associated with ovulatory cycles, 3. Anovulatory cycles and prolonged cycles become more frequent as the menopause approaches, resulting in dysfunctional uterine bleeding (DUB) and oligomenorrhea. Manifestations of hormonal fluctuation 1. Menstrual cycle changes. a. Menorrhagia Increased flow may result from a relative reduction in progesterone levels. b. Metrorrhagia or polymenorrhea c. Midcycle spotting. With a drop in estradiol levels just before ovulation, midcycle estrogen withdrawal bleeding may occur. d. Oligomenorrhea. As the menopause approaches, 2. Other symptoms a. Hot flushes or flashes. b. Headaches. Premenstrual migraines may appear or worsen during this time. c. Premenstrual psychological symptoms. d. Sleep disturbances. CLINICAL MANIFESTATIONS OF MENOPAUSE Urogenital atrophy. The vaginal epithelium becomes pale, thin, and dry vaginal walls lose elasticity and compliance; the vagina becomes smaller, and the size of the upper vagina diminishes The labia minora have a pale, dry appearance, and there is a reduction of the fat content of the labia majora. The pelvic tissues and ligaments that support the uterus and the vagina lose their tone, predisposing to disorders of pelvic relaxation The epithelium of the urethra and bladder mucosa becomes atrophic; there is a loss of urethral and bladder wall elasticity and compliance 2. Uterine changes a. The endometrial tissue becomes sparse, with an atrophic appearance. b. The myometrium atrophies, and the uterine corpus decreases in size. c. The squamocolumnar junction relocates high in the endocervical canal; the cervical os frequently becomes stenotic. d. Fibroids, if present, reduce in size but do not disappear. 3. Breast changes a. Progressive fatty replacement with atrophy of active glandular units b. Regression of fibrocystic changes Others 4. Skin changes. Skin collagen content and skin thickness decrease proportionately with time after the menopause. 5. Bone changes. Bone loss is accelerated for the first 5 to 7 years after the menopause associated with decreased estrogen levels. a. The greatest effect is seen in trabecular bone, particularly in the spine. b. Excessive loss predisposes to the development of osteoporosis and increased fracture risk. 6. Hair changes. As estrogen decreases, circulating androgens increase and the chance of developing increased facial hair and androgenic alopecia increases. 7. Brain changes. Estrogen receptors are located throughout the brain. Reduced estrogen levels may affect cognitive function and moods after the menopause, although the precise contribution has not been fully defined. 8. Cardiovascular changes. The incidence of cardiovascular disease increases after the age of 50 years in women coincident with the age of menopause. Cardiovascular disease is the cause of the largest number of deaths of menopausal women. Symptoms related to estrogen reduction 1. Vasomotor instability Hot flushes or flashes are the most common symptom related to the menopause and occur in 75 to 85% of perimenopausal women. (1) more frequent and severe at night or during times of stress. (2) They also can be precipitated by foods and beverages that are hot or spicy or contain methylxanthines; they can be precipitated by alcohol as well. (3) The vasomotor instability lasts for I to 2 years in most women but may last for as long as 5 years or more in up to one third of symptomatic women. Hot flushes are the result of inappropriate stimulation of the body's heatreleasing mechanisms by the thermoregulatory centers in the hypothalamus. Although the core body temperature is normal, the body is stimulated to lose heat. The onset of the flushes initially depends on a reduction of previously established estrogen levels. Flushes are characterized by progressive vasodilation of the skin over the head, neck, and chest, accompanied by reddening of the skin, a feeling of intense body heat, and perspiration. Palpitations or tachycardia may accompany the flush. The flush may last a few seconds to several minutes and recur with variable frequency. Treatment (1) Hormone replacement or estrogen replacement reduces or eliminates hot flushes. (2) Progestins, clonidine, methyldopa, vitamin E, and herbal remedies are used to treat hot flushes in women in whom estrogen is contraindicated. Relief is not as complete as that seen with estrogen therapy. (3) Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, given in low doses has been effective in reducing or eliminating vasomotor instability in 60% of symptomatic women. 2. Altered menstrual function. Oligomenorrhea is followed by amenorrhea. If vaginal bleeding occurs after 6 months of amenorrhea, endometrial disease (e.g., polyps, hyperplasia, or neoplasia) must be ruled out. 3. Vaginal atrophy a. Dyspareunia (painful intercourse). (1) Changes in the vaginal epithelium and vaginal vasculature lead to decreased lubrication during sexual activity. Decreased compliance and elasticity of the vaginal wall contribute to vaginal stenosis. (2) Continued sexual activity into the menopause is associated with increased vaginal blood flow and fewer problems with sexual function compared with women who are less frequently sexually active. b. Atrophic vaginitis (1) The postmenopausal vagina becomes more susceptible to pathogenic and nonpathogenic organisms. (2) Atrophy of the vaginal mucosa and changes in pH predispose to vaginitis, which presents with symptoms of discharge, pruritus, odor, and irritation. c. Treatment. Symptoms related to vaginal atrophy respond to estrogen therapy. 4. Urinary tract symptoms Changes in the mucosal lining of the urethra and bladder may lead to symptoms of dysuria, nocturia, urinary frequency, urgency, and urge incontinence. Urinary stress incontinence may progressively worsen after the menopause because of urethral changes and a loss of pelvic support. There is an increased incidence of bacteriuria b. Treatment. Vaginal, urethral, and bladder symptoms improve with estrogen therapy. 5. Osteoporosis . This systemic skeletal disease is characterized by low bone mass and microarchitectural deterioration of bone structure Both result in fragile bones that are at an increased risk for fracture. Osteoporosis may be a primary disease state or may be secondary to other diseases that affect calcium and bone metabolism. Epidemiology and etiology (1) Peak bone mass is reached in the late twenties for trabecular bone and the early thirties for cortical bone. (2) Thereafter, there is a gradual loss of bone with aging. (3) Bone loss is accelerated for the first 5 to 7 years after the menopause as a direct result of declining estrogen levels. Problem size In the United States; An estimated 1.3 million fractures occur annually. Approximately 25% of white American women older than 60 years of age who are not treated with estrogen replacement have spinal compression fractures. Approximately 32% of white American women older than 75 years of age suffer hip fractures; Risk factors Inadequate calcium intake Sedentary lifestyle Smoking Alcohol use Thinness premature menopause genetic predisposition white and Asian race Steroid and thyroxine use. Diagnosis Imaging modalities can be used to detect bone loss and bones at risk for fracture earlier in the disease. (1) Dual-energy x-ray absorptiometry is the most popular technique used today to measure bone density. Independent measurements can be made at the hip, spine, and other bone sites. (2) Quantitative computed tomography gives the most precise measurement of bone density at specific sites. However, its use has been limited by expense and higher radiation doses. Prevention of osteoporosis Exercise adequate calcium intake (early) estrogen replacement after the menopause The higher a woman's bone mineral density at the onset of menopause, the less risk of fracture. Treatment Calcitonin √ Fluoride X Androgens X bisphosphonates (alendronate, etidronate disodium, risedronate)√ SERMs (selective estrogen receptor modulators such as raloxifene). √ HRT: not therapeutic Regimens of HRT 1. Unopposed estrogen. This is the treatment of choice in women who have undergone hysterectomy. If not, Endometrial biopsy on an annual basis is recommended. 2. Sequential combined therapy. Estrogen is administered every day, and progestogen is administered for 12 to 14 days every month. Scheduled bleeding should occur on completion of the progestogen. 3. Continuous combined therapy a. Estrogen and progestogen are administered daily. (1) There is no scheduled withdrawal bleeding. (2) Symptoms that worsen with hormonal fluctuations, including mood disturbances, migraines, and cyclic mastalgia, are improved. (3) The regimen is easy for patients to remember. But irregular spotting and bleeding in up to 40% of women during the first year. 4. Periodic or quarterly progestogen X a. Progestogen is administered for 14 days once every 3 months b. Withdrawal bleeding may be heavy 5. Local applications a. Topical estrogen is used intravaginally to treat symptoms of urogenital atrophy and dyspareunia. Estrogen-containing creams, tablets, and synthetic rings are available for this use. b. Peak systemic absorption is in the first few days of initial use. Once the vaginal mucosa becomes cornifled, there is minimal systemic absorption of estrogen. c. Progestin intrauterine devices are being used as a way to provide endometrial protection and avoid the side effects of systemic progestin. Route 1. Estrogens. Estrogens, for the purpose of replacement, are administered orally or transdermally or locally 2. Progestogens medroxyprogesterone acetate. Starting doses depend on the regimen used. (1) 5 mg for 12 days monthly for sequential therapy (2) 2.5 or 5 mg for continuous regimens