Chapter 61
Estrogens and Progestins:
Basic Pharmacology and
Noncontraceptive Applications
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Estrogens and Progestins
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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The Menstrual Cycle
Follicular
phase—first
half of the cycle
(days 1–14)
Full cycle
typically
takes 28
days
Luteal
phase—
second half
of the cycle
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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The Menstrual Cycle
Coordinating ovarian and
uterine events
Uterine changes are brought
about under the influence of
estrogens and progesterone
Anterior pituitary hormones, folliclestimulating hormone (FSH), and
luteinizing hormone (LH) regulate the
menstrual cycle
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Estrogens
Biosynthesis and elimination
 Female
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Estrogens

Effects on primary and secondary sex
characteristics
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Estrogens

Metabolic actions
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Positive effect on bone mass
Favorable effects on cholesterol levels
Blood coagulation
Adverse effects
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Endometrial hyperplasia and carcinoma
Promotes growth of existing breast cancer
Ovarian cancer
Cardiovascular events
Nausea
Adverse effects from use during pregnancy
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Estrogens
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Therapeutic uses
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Hormone therapy after menopause
Female hypogonadism
Acne
Routes of administration

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Oral
Transdermal
Intravaginal
Parenteral
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Selective Estrogen Receptor
Modulators (SERMs)
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Selective Estrogen Receptor
Modulators (SERMs)

Tamoxifen (Nolvadex)

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Activates estrogen
Breast cancer treatment: inhibits cell growth in the
breast
Protects against osteoporosis
Produces hot flashes
Risk for endometrial cancer and thromboembolism
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Selective Estrogen Receptor
Modulators (SERMs)

Raloxifene (Evista)

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Does not activate estrogen
Protects against breast cancer, osteoporosis
Promotes thromboembolism
Induces hot flashes
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Progestins

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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Progestins
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Therapeutic uses
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
Postmenopausal hormone therapy
Dysfunctional uterine bleeding
Amenorrhea
Prematurity prevention
Endometrial carcinoma and hyperplasia
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Menopausal Hormone
Therapy Benefits
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Menopausal Hormone
Therapy Benefits
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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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Menopausal Hormone
Therapy Risks

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Cardiovascular events: myocardial infarction,
stroke, pulmonary embolism, and deep
venous thrombosis
Endometrial cancer
Breast cancer
Ovarian cancer
Gallbladder disease
Dementia
Urinary incontinence
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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