Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download HRT
Document related concepts
no text concepts found
Transcript
Hormone replacement therapy (HRT) is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women. It involves the use of one or more of a group of medications designed to artificially boost hormone levels. The main types of hormones involved are oestrogens, progesterone or progestins, and sometimes testosterone. Menopause is the permanent cessation of menses following the loss of ovarian follicular activity. It is a physiologic event that occurs after 12 consecutive months of amenorrhea—so the time of the final menses is determined retrospectively. Women who have undergone hysterectomy must rely on their symptoms to estimate the actual time of menopause. It occurs at the age of late 40’s and early 50’s Average age is 51and average life expectancy is 81 years. It is genetically predetermined. Approximately 1% of women develop ovarian failure before the age of 40 years (premature menopause or premature ovarian failure). It may be due to chemotherapy, radiation, extensive ovarian surgery, X-chromosome abnormalities, as a component of autoimmune syndrome (hypothyroidism, hypoparathyroidism , monocutaneous candidiasis), enzyme deficiencies , Gonadotropin receptor abnormalities etc. Perimenopause : The perimenopause is the period immediately prior to the menopause and the first year after menopause. The menopausal transition usually begins approximately 4 years prior to menopause and is characterized by menstrual cycle irregularity caused by increased frequency of anovulatory cycles. Postmenopause : The term postmenopause is applied to women who have not experienced a menstrual bleed for a minimum of 12 months. Responsible for all the pubertal changes. ( growth of uterus , fallopian tubes and vagina) Maintains bone mass primarily by retarding bone resorption. Osteoclast pit formation is inhibited and there is increased expression of bone matrix proteins such as osteonectin, osteocalcin, collagen and alkaline phosphatase. Maintains positive calcium balance , partly by inducing renal hydroxylase enzyme which generates active form of vit-D3. Decreases plasma LDL cholesterol while HDL levels and triglycerides levels are raised. Induces the synthesis of clotting factors (factors 2, 7, 9 and 10) Increases lithogenecity of bile by increasing cholesterol secretion and reducing bile salt secretion. Induce nitric oxide synthase in vascular endothelium and promote vasodilation. Plasma levels of sex harmone binding globulin (SHBG), thyroxine binding globulin (TBG), cortisol binding globulin (CBG) are elevated - but without any change in harmonal status. Has secretory activity on uterine wall. Converts the watery cervical secretions induced by estrogens to viscid, scanty and cellular secretion hostile to sperm penetration. Induce pregnancy like changes in the vaginal mucosa. Prepares breast for lactation during pregnancy. High circulating conc during pregnancy appears to have a sedative effect. It causes a slight (o.5 degree centigrade) rise in body temperature by resetting the hypothalamic thermostat and increasing heat production. Progestins in relatively higher doses stimulate respiration , as occurs during pregnancy. Raise LDL levels and lower HDL levels. Progesterone is a weak inhibitor of gonadotropin secretion from pituitary. It decreases the frequency of LH pulses by action on hypothalamic pulse generator but increases the amount of LH secreted per pulse. Osteoporosis Cardiovascular disease Vasomotor instability Cholesterol elevation Sexual dysfunction Affective disorders Alzheimer's disease VASOMOTOR SYMPTOMS Hot flush (coincide with increases in LH, ACTH, and cortisol levels, but are not the cause) Night sweats and inappropriate sweating. Chilly sensations Symptoms increases as estrogen level declines Variable in severity, can persist for years Vaginal atrophy Urinary urgency Vaginal dryness and change in pH Nocturia Vulval shrinkage Itching Dyspareunia Predisposition to urinary tract infection Irritability Lethargy/Fatigue Depression Loss of Libido Sexual dysfunction Insomnia Difficulty with concentration Anxiety and dementia Loss of osteoid as well as calcium Thinning and weakening of bone Minimal trauma fractures especially of femur, hip , radius, vertebrae. Dermatological changes Thinning of skin Drying and loss of elasticity of skin Wrinkles Thin and listless hair Other changes include increased risk of cardiovascular diseases such as Coronary Artery Disease (CAD) Myocardial Infarction (MI) Stroke The vasomotor changes subside over a few years , but other changes progresses continuosly. Since estrogen therapy relieves symptoms and improve HDL:LDL ratio, retard atherogenesis , reduce arterial impedance , prevent osteoporosis , it was believed that estrogen therapy in postmenopausal woman will have a protective cardiovascular influence. A segment of doctors contended that menopausal women should take HRT for the rest of their lives. But the studies conducted by “ Women’s Health Initiative” (WHI) and many cohort studies and placebo studies yielded opposite results. It was concluded that the risks associated with HRT are more than the benefits. The study 16,608 younger women Women ages 50-79 Purpose was to identify risks and benefits of long-term HRT use Use of both estrogen and progestin in combination Stopped prematurely because of findings( occurrence of prespecified level of invasive breast cancer ) The primary outcome was coronary heart disease events, defined as nonfatal myocardial infarction and coronary artery disease death, with invasive breast cancer as the primary adverse outcome. The study also examined secondary outcomes, including stroke, thromboembolic disease, fractures, colon cancer, and endometrialcancer. Results 26 percent increase of invasive breast cancer 29 percent increased risk of death from coronary heart disease 41 percent increased risk of stroke 200 percent increased risk of blood clots Limitations to the study Breast cancer In 2003 there was 14,000 less cases of breast cancer possibly due to the decrease in women taking HRT If a woman is diagnosed with breast cancer while taking HRT, she is advised to stop immediately. Endometrial cancer Cardiovascular disease Stroke Blood clots Maintains thickness and vascularity of vaginal and urethral tissue for comfort and lubrication during sexual interaction . Treatment of Vaginal atrophy. Reduces hot flashes and sleep disturbances from night sweats. Protects against osteoporosis and resultant fractures, particularly of the hip. Reduces risk of colon cancer when used in combination therapy. CANDIDATES FOR HRT Symptomatic patients at the time of menopause Premature ovarian failure patients Surgically menopausal patients As a treatment for Osteoporosis CONTRAINDICATIONS FOR HRT Breast cancer patients Endometrial cancer patients Pregnant patients Thromboembolic hx (DVT, PE) Hypercoaguability disorders Liver disease Undiagnosed genital bleeding Lowest dose for shorter duration is recommended. Therapy directed at menopausal symptoms, such as hot flushes, is often short term. However, therapy directed at prevention of osteoporosis should be long term. In women with an intact uterus, hormone therapy consists of an estrogen plus a progestogen. Inwomen who have undergone hysterectomy, estrogen therapy is given unopposed by a progestogen. Estrogen Orally Transdermal patches Topical gels or creams Vaginal cream or pills Injectable Progesterone Orally Topical Vaginal cream Injectable DRUG DOSE FREQUENCY ROUTE Conjugated equine 0.3 - 0.45 mg estrogen OD Oral Esterified estrogens OD Oral Estropipate 0.625mg (piperazine estrone sulfate) OD Oral Ethinyl estradiol 5mcg OD Oral Micronized 17βestradiol 1–2 mg (0.25-0.5mg) OD Oral Transdermal 17βestradiol 50 mcg (25 mcg) Once or twice weekly Transdermal Intranasal 17βestradiol 150 mcg, OD Intranasally Implanted 17βestradiol 50 to 100 mg( 25mg) every 6 months. subcutaneously 0.3 mg DRUG DOSE FREQUENCY ROUTE 17β-estradiol emulsion -0.05 mg, gel- 0.04 mg OD Transdermal (Percutaneous) Vaginal rings (Estring , Femring). PROGESTERONES : Due to increased risk of endometrial hyperplasia and endometrial cancer with estrogen monotherapy (unopposed estrogen), women who have not undergone hysterectomy should be treated concurrently with a progestogen in addition to the estrogen. Progestogens must be taken for a sufficient period of time during each cycle. A minimum of 12 to 14 days of progestin therapy each month is required for complete protection against estrogeninduced endometrial hyperplasia. Even low dose estrogen should contain progesterone for endometrial protection . Various progestogens used are : Dydrogesterone Medroxy progesterone acetate Micronized progesterone Norethisterone Norethindrone acetate Norgestrel Levonorgestrel Most commonly used oral progestogens are medroxyprogesterone acetate, micronized progesterone,and norethisterone acetate. Methods of Estrogen and Progestogen Administration Continuous Cyclic Estrogen/Progestogen Treatment. Continuous-Combined Estrogen/Progestogen Treatment. Continuous Long-Cycle Estrogen/Progestogen Treatment. Intermittent-Combined Estrogen/Progestogen Treatment. Continuous-Cyclic Estrogen taken daily Progestogen for 12 -14 days of a 28 cycle. Progestogen causes scheduled withdrawl bleeding in 90% women. Continuous-Combined Both are given daily . Best reserved for women who are at least 2 years postmenopause. Continuous Long-Cycle Estrogen is given daily,and progestogen is given six times a year, every other month for 12 to 14 days, resulting in six periods a year. Bleeding episodes may be heavier and last for more days than withdrawal bleeding with continuous-cyclic regimens. Intermittent-Combined : 3 days of estrogen therapy alone, followed by 3 days of combined estrogen and progestogen and repeating the same. Designed to lower the incidence of uterine bleeding. ANDROGENS Given primarily to patients who have undergone surgical menopause . Testosterone treatment should not be administered to postmenopausal women who are not receiving concurrent estrogen therapy. Estrogen combined with androgen increases bone density sooner and to a greater degree than estrogen therapy ANDROGEN Regimen for women DRUG DOSE FREQUENCY ROUTE Methyltestosterone + Esterified Estrogen Mixed testosterone esters 50–100 mg Every 4 to 6 weeks Intramuscular Testosterone pellets 50 mg Every 6 months Subcutaneous (implanted) testosterone system 150–300 mcg/day Every 3 to 4 days Transdermal Nandrolone decanoate 50mg every 8-12 weeks Intramuscular ESTROGENS Breast tenderness Abnormal bleeding Nausea Increased incidence of GB disease Stimulation of preexisting estrogen dependent tumor Increases sex hormone binding globulin PROGESTOGENS Weight gain Moodiness Acne Carbohydrate intolerance Break through bleeding Bloating ANDROGENS Weight gain Hirsuitism Lowering of the voice Acne Oiliness of the skin Decreases sex hormone binding globulin Selective estrogen-receptor modulators (SERMs), Tamoxifen, the first-generation SERM, It has estrogen antagonist activity on the breast and estrogenlike agonist activity on bone and endometrium. Ex: raloxifene, prevent bone loss and spinal fractures. Used for preventing osteoporosis in women contraindicated to HRT. Tibolone It is a gonadomimetic synthetic steroid in the norpregnane family with combined estrogenic, progestogenic, and androgenic activity. For the treatment of menopausal symptoms and prevention of osteoporosis. Tibolone has beneficial effects on mood and libido and improves menopausal symptoms and vaginal atrophy. Tibolone protects against bone loss, and its effect on fracture rates is currently being evaluated. Black cohosh (Cimicifuga racemosa) is used widely and has been shown to be an effective alternative for the relief Of vasomotor symptoms (may act through serotonergic system). Soy isoflavones in soy products Relieves a number of symptoms, including hot flashes, night sweats, fatigue and vaginal dryness Soy has also been shown to assist the body in absorbing and retaining calcium, suppress bone loss, lower LDL cholesterol and decrease blood clotting Alternatives to treat vasomotor symptoms SNRIs( Serotonin Norepinephrine reuptake inhibitors) —Venlafaxine (Effexor) shows good results SSRIs ( Selective Serotonin Reuptake Inhibitor) — Paroxetine with good data, fluoxetine less but helpful Megestrol Acetate (synthetic progestin)—hot flash reduction of 85% vs 21% for placebo (wt gain side effect) Clonidine- alpha-2 adrenergic agonist Consider in women with hypertension Gabapentin—unknown mechanism, generally demonstrates reduction in hot flashes Pre treatmemt assessment should be done and the patient should be explained with risks and benefits so that they can outweigh them Should consider parameters like coronary artery disesase risk , thromboembolism risk , breast cancer and osteoporosis . Recommendations should be specific to each woman and her background. The main indication for hormone therapy is to relieve from menopausal symptoms, and hormone therapy should be used only as long as symptom control is necessary (typically for about 2 to 3 years). When used under such conditions, the absolute risk of harm to an individual woman is very small . Recommended for not more than 5 years. Pharmacotherapy , A Pathophysiologic approach by Joseph T. Dipiro . Textbook of therapeutics drug and disease management . By Herfindal ,Gourley. 7th edition. Essentials of medical physiology by KD Tripathi. Human physiology by Dr.C.C.Chatterjee , volume -2 Hormone replacement therapy - wikipedia , google. ANY QUESTIONS ????
