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Chapter 61

Chapter 61. Estrogens and Progestins: Basic Pharmacology and Noncontraceptive Applications. Estrogens and Progestins. Hormones with multiple actions Promote female maturation Help regulate ongoing activity of female reproductive organs

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Chapter 61

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  1. Chapter 61 Estrogens and Progestins: Basic Pharmacology and Noncontraceptive Applications

  2. Estrogens and Progestins • Hormones with multiple actions • Promote female maturation • Help regulate ongoing activity of female reproductive organs • Estrogens affect bone mineralization and lipid metabolism • Principal endogenous estrogen is estradiol; principal progestational hormone is progesterone

  3. The Menstrual Cycle

  4. The Menstrual Cycle

  5. Estrogens Biosynthesis and elimination • Female • Ovary is the principal organ • Follicles, then corpus luteum • Placenta produces large amounts pregnancy • Major estrogen produced is estradiol • Male • Small amounts of testosterone converted into estradiol and estrone by the testes • Peripheral tissues

  6. Estrogens • Effects on primary and secondary sex characteristics • Reproductive tract and secondary sex characteristics • Physiologic processes related to reproduction • (1) ductal growth in the breast • (2) thickening and cornification of the vaginal epithelium (3) proliferation of the uterine epithelium • (4) copious secretion of thickened mucus from endocervical glands

  7. Estrogens • Metabolic actions • Positive effect on bone mass • Favorable effects on cholesterol levels • Blood coagulation • Adverse effects • Endometrial hyperplasia and carcinoma • Promotes growth of existing breast cancer • Ovarian cancer • Cardiovascular events • Nausea • Adverse effects from use during pregnancy

  8. Estrogens • Therapeutic uses • Hormone therapy after menopause • Female hypogonadism • Acne • Routes of administration • Oral • Transdermal • Intravaginal • Parenteral

  9. Selective Estrogen Receptor Modulators (SERMs) • Activate in some tissues and block estrogen receptors selectively in others • Developed to provide benefits of estrogen while avoiding the drawbacks • Three available • None of the three offers all the benefits of estrogen and avoid all the drawbacks

  10. Selective Estrogen Receptor Modulators (SERMs) • Tamoxifen (Nolvadex) • Activates estrogen • Breast cancer treatment: inhibits cell growth in the breast • Protects against osteoporosis • Produces hot flashes • Risk for endometrial cancer and thromboembolism

  11. Selective Estrogen Receptor Modulators (SERMs) • Raloxifene (Evista) • Does not activate estrogen • Protects against breast cancer, osteoporosis • Promotes thromboembolism • Induces hot flashes

  12. Progestins • Compounds that act like progesterone • Principal endogenous progestational hormone • Produced by ovaries and placenta • Adverse effects • Teratogenic effects • Gynecologic effects • Breast cancer • Depression • Breast tenderness

  13. Progestins • Therapeutic uses • Postmenopausal hormone therapy • Dysfunctional uterine bleeding • Amenorrhea • Prematurity prevention • Endometrial carcinoma and hyperplasia

  14. Menopausal Hormone Therapy Benefits • Relief of vasomotor symptoms • Management of urogenital atrophy • Prevention of osteoporosis and related fractures • Cardioprotection • Prevention of colorectal cancer • Positive effect on wound healing • Tooth retention • Glycemic control

  15. Menopausal Hormone Therapy Benefits • Physiologic doses of estrogen (with or without progestin) • Taken to manage symptoms caused by loss of estrogen in menopause • Hot flashes, sleep disturbances, urogenital atrophy, bone loss, altered lipid metabolism • Use of hormone replacement therapy (HRT) has declined sharply • Landmark studies: WHI and HERS

  16. Menopausal Hormone Therapy Risks • Cardiovascular events: myocardial infarction, stroke, pulmonary embolism, and deep venous thrombosis • Endometrial cancer • Breast cancer • Ovarian cancer • Gallbladder disease • Dementia • Urinary incontinence

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