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Transcript
Menopause Drugs 1 Menopause: permanent cessation of menses following the loss of ovarian follicular activity Defined as 12 consecutive months of amenorrhea Caused by: aging (natural menopause), surgery (hysterectomy), medications, pelvic irradiation Signs and Symptoms of Menopause: Symptoms: vasomotor (hot flash/night sweat), sleep disturbances, mood changes, sexual dysfunction, memory difficulties, vaginal dryness, dyspareunia, arthralgia Signs: menstrual cycle irregularity (perimenopause), urogenital atrophy (menopause) Labs: FSH > 10-20 (perimenopause) or > 40 (menopause) Metabolic Changes: wt redistribution ( central abdominal fat); lipid profile; vascular function; bone metabolism Considerations for HT: severity of symptoms, osteoporosis risk, CV dz, breast CA, thromboembolism Drug Class Drug Layer clothing Nonpharmacologic Lower room temp Decrease hot/spicy food, caffeine, hot beverages Exercise Yoga Acupuncture MOA Pharmacokinetics/ dynamics Indications AE/DI/CI Other Menopause Drugs 2 Drug Class Drug MOA Pharmacokin/dynam Indications AE/DI/CI Other Estrogen Inhibits ovulation by suppressing FSH and LH Oral Transdermal Topical Intravaginal IM Most effective option for alleviating vasomotor symptoms, vaginal symptoms, and improving sleep quality FDA -approved AE: Nausea HA Breast tenderness Bleeding triglycerides Coagulation parameters Minimize Risks via: (prescribed +/progestogen) Hormone Therapy Alters secretions and cellularity of the endometrium Conjugated equine estrogens 17 β- estradiol Oral forms are metabolized by Induces luteolysis GI mucosa and the liver with Provides cycle high first pass control Non-oral forms bypass the GI and have less effect on lipids and coag Relief of: Vasomotor sympt. Atrophic vaginitis Prevention of postmenopausal osteoporosis Low systemic concentrations w/ intravaginal preparations Benefits: bone resorption (prevent osteoclast maturation and induce apoptosis) LDL HDL risk of colon CA CI to HT: Active liver dz, Thromboembolic dz, Breast CA, Estrogen sensitive malignancy, Known hypersensitivity, Prophyria cutanea tarda, Undiagnosed genital bleeding, Untreated endometrial hyperplasia, Untreated HTN Risks: risk of gallstones risk of VTE risk of breast CA triglycerides (CV dz increased in 1st two years of HT) Limiting duration of use Using the lowest required dose Attempting D/C annually Smoking cessation Menopause Drugs 3 Drug Class Drug MOA Pharmacokin/dynam Indications AE/DI/CI Other Progestogen Inhibits ovulation by suppressing the LH mid-cycle surge Oral Transdermal Most effective option for alleviating vasomotor symptoms, vaginal symptoms, and improving sleep quality AE: Irritability Depression HA Minimize Risks via: (prescribed with estrogen therapy) Hormone Therapy Inhibits implantation by suppressing the endometrium Medroxyprogest- Thickens cervical mucus erone acetate (MDPA) (Provera) Slows tubal motility and Micronized delays sperm progesterone (Prometrium) transport Norethindrone acetate Increases basal insulin levels and insulin response to glucose Stimulates lipoprotein lipase activity fat deposition Metabolized in the liver to inactive products Excreted in the urine Indicated for women who have NOT undergone a hysterectomy Other Indications: Contraception Dysfunctional uterine bleeding Note: NOT used in cases with hysterectomy since progesterone is used to balance uterine hyperplasia and decrease cancer risk with estrogen use CI to HT: Active liver dz, Thromboembolic dz, Breast CA, Estrogen sensitive malignancy, Known hypersensitivity, Prophyria cutanea tarda, Undiagnosed genital bleeding, Untreated endometrial hyperplasia, Untreated HTN Limiting duration of use Using the lowest required dose Attempting D/C annually Smoking cessation Menopause Drugs 4 Selective Estrogen Receptor Modulators (SERMs) Selective Estrogen Receptor Modulators (SERMs) Drug Class Drug MOA Tamoxifen Chemically distinct from estradiol (nonsteroidal compounds) Toremifene Pharmacokin/dynam Indications AE/DI/CI Breast CA Acts as an agonist in bone and in coagulation Acts as an antagonist in the breast and vasomotor center Raloxifene (Evista) Chemically distinct from estradiol (nonsteroidal compounds) Acts as an agonist in bone and in coagulation Acts as an antagonist in the breast, uterus, and vasomotor centers Metabolized extensively in the liver Prevention And Treatment of Osteoporosis Excreted in the feces Reduction of invasive breast CA in high risk women Highly protein bound NOT useful for menopausal symptoms (see AEs) AE: Does NOT alleviate hot flashes May EXACERBATE hot flashes Leg cramps Increased risk of thromboembolism Other Menopause Drugs 5 Selective Estrogen Receptor Modulators (SERMs) Drug Class Drug MOA Pharmacokin/dynam Indications AE/DI/CI Ospemifene (Osphena) Chemically distinct from estradiol (nonsteroidal compounds) Metabolized via: CYP3A4 CYP2C9 CYP2C19 Moderate severe dyspareunia Vulvar and vaginal atrophy AE: risk of DVT risk of PE Hot flushes Vaginal discharge Muscle spasm Genital discharge Hyperhidrosis (excessive sweating) Acts as an agonist in bone, endometrium, and in coagulation Acts as an antagonist in the breast and vasomotor center DI: Fluconazole (inhibits metabolism) Ketoconazole (inhibits metabolism) Rifampin (induces metabolism) Use with progestin if uterus is present due to agonistic actions on endometrium Other Menopause Drugs 6 Selective Estrogen Receptor Modulators (SERMs) Drug Class Drug MOA Bazedoxifene Chemically distinct from estradiol (nonsteroidal compounds) Acts as an agonist in bone and in coagulation Combination Estrogen + SERM Conjugated estrogens + Bazedoxifene (DuaVee) Acts as an antagonist in the breast, uterus, and vasomotor centers Combination of estrogen and estrogen agonist/ antagonist (SERM) Pharmacokin/dynam Indications Menopausal vasomotor symptoms Prevention of postmenopausal osteoporosis (in combination with estrogen) Used to decreased endometrial hyperplasia with estrogen therapy BMD in spine and hip (bone mineral density) But NO fx data available Treatment of menopausal vasomotor symptoms Prevention of postmenopausal osteoporosis AE/DI/CI Other Menopause Drugs 7 Drug Class Drug MOA Bisphosphonates Inhibits bone resorption (depth) to produce a positive bone balance via shortening the life span of osteoclasts Bisphosphonates Alendronate (Fosamaz) Risedronate (Actonel) Pharmacokin/dynam Indications AE/DI/CI Prevention And Treatment of osteoporosis AE: GI disturbances Difficulty swallowing Heartburn Esophagitis/ulceration Abdominal pain Osteonecrosis of jaw Prevention of osteoporosis AE: Constipation Intestinal bloating Excess gas Ibandronate (Boniva) Zoledronate (Reclast) Vitamins Minerals Calcium Vitamins Minerals Vitamin D Prevention of osteoporosis DI: Certain antibiotics AE: Well-tolerated Other Menopause Drugs 8 Drug MOA Calcitonin (Miacalcin) (Fortical) Teriparatide (Forteo) Synthetic Vitamins Minerals Drug Class Indications AE/DI/CI Inhibits bone resorption via reducing the life span of osteoclasts Treatment of osteoporosis AE: Nasal irritation, rhinitis Epistaxis HA Arthralgia Synthetic human parathyroid hormone Treatment of osteoporosis AE: Nausea Muscle cramps Hypercalcemia Transient hypotension Treatment of osteoporosis AE: Back and MSK pain Serious infection Dermatologic rxn Hypercholesterolemia Activates osteoblasts to stimulate new bone formation Denosumab (Prolia) Monoclonal Antibody Pharmacokin/dynam Human IgG2 monoclonal antibody inhibits RANK ligand Inhibits osteoclast formation, function, and survival Decreases bone resorption and increases bone mass and strength Other Menopause Drugs 9 Androgens Drug Class Drug MOA Pharmacokin/dynam Indications AE/DI/CI Testosterone Oral (daily) Methyltestosterone in combination with esterified estrogens Transdermal (q6mo) Lack of documented clinical and biochemical findings of androgen deficiency in women AE: Increased facial/body hair (virilization) Increased acne Reduced HDL Fluid retention Subcutaneous (q3-4days) However, still being used for: Diminished well-being Unexplanied fatigue Decreased libido Decreased sexual receptivity and pleasure CI: Androgen-dependent CA Moderate/severe acne Hirsuitism Androgenic alopecia Long-term safety unknown Other Menopause Drugs 10 Drug Class Drug MOA Pharmacokin/dynam Hot flushes Tibolone Venlafaxine Desvenlafaxine Paroxetine: CYP2D6 inhibitor Paroxetine Megesterol acetate Other Estrogen Alternatives Clonidine Gabapentin Citalopram Sertraline Fluoxetine Tamoxifen Indications Fluox: CYP2D6 inhibitor Tamox: estrogen receptor blockade Tamoxifen: metabolized by CYP2D6 to endoxifen AE/DI/CI Other Menopause Drugs 11 Other Alternatives Drug Class Drug MOA Black cohosh Cimicifuga racemosa Indications AE/DI/CI Estrogenic properties vs serotonergic effects Possibly effective for menopausal symptoms AE: Hepatotoxicity Plants compounds with estrogen-like activity Hot flushes Menopausal symptoms Isoflavones Lignans Coumestans Soy beans Cereals Flaxseed (lignans) Alfalfa Sprouts (coumestans) Other Alt St. John's wort Supplements Water-soluble lubricants Other Alternatives Other Remifemin Phytoestrogens Other Alternatives Pharmacokin/dynam Lubricant: temporary, short duration AE: Compromises condom integrity Decreased sperm motility Moisturizer: long-term relief bioadhesive polycarbophilbased polymer attaches to mucin and epithelial cells AE: Lowers vaginal pH Spermicidal activity in vitro And Moisturizers Replens