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

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 2

3. The Menstrual Cycle
Follicular phase—first half of the cycle (days 1–14)
Luteal phase—second half of the cycle
Full cycle typically takes 28 days 3

4. The Menstrual Cycle Coordinating ovarian and uterine events
Uterine changes are brought about under the influence of estrogens and progesterone
Anterior pituitary hormones, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) regulate the menstrual cycle 4

5. Estrogens Biosynthesis and elimination Female Male
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 5

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 Adverse effects
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 7

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

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 9

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 11

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 12

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

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 14

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 15

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 16