Chapter 61
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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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Chapter 61

Chapter 61

Estrogens and Progestins: Basic Pharmacology and Noncontraceptive Applications


Estrogens and progestins

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


The menstrual cycle

The Menstrual Cycle


The menstrual cycle1

The Menstrual Cycle


Estrogens

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


Estrogens1

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


Estrogens2

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


Estrogens3

Estrogens

  • Therapeutic uses

    • Hormone therapy after menopause

    • Female hypogonadism

    • Acne

  • Routes of administration

    • Oral

    • Transdermal

    • Intravaginal

    • Parenteral


Selective estrogen receptor modulators serms

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


Selective estrogen receptor modulators serms1

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


Selective estrogen receptor modulators serms2

Selective Estrogen Receptor Modulators (SERMs)

  • Raloxifene (Evista)

    • Does not activate estrogen

    • Protects against breast cancer, osteoporosis

    • Promotes thromboembolism

    • Induces hot flashes


Progestins

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


Progestins1

Progestins

  • Therapeutic uses

    • Postmenopausal hormone therapy

    • Dysfunctional uterine bleeding

    • Amenorrhea

    • Prematurity prevention

    • Endometrial carcinoma and hyperplasia


Menopausal hormone therapy benefits

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


Menopausal hormone therapy benefits1

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


Menopausal hormone therapy risks

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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