MODULE 4:
PHARMACOLOGY OF SEX
HORMONES
Molly Downing, PhD
Clinical Instructor
College of Pharmacy
downing.211@osu.edu
2
Objectives
• Define endocrine system, hormones, and glands.
• Explain the regulation of sex hormone synthesis and release.
• Explain the mechanism of action and adverse effects of
hormonal contraceptives.
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Roadmap
1. The basics of hormone signaling
2. Female & Male Sex Hormones
3. Clinical & Non-clinical Uses
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Terminology
• Endocrine system: glands that
secrete hormones into the
bloodstream to regulate growth,
metabolism, or reproduction
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Terminology
• Endocrine system: glands that
secrete hormones into the
bloodstream to regulate growth,
metabolism, or reproduction
• Hormone: substance secreted into
the bloodstream that acts at a distant
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Types of endocrine hormones
The pancreas The ovaries secrete
secretes insulin (a estrogen (a steroid)
polypeptide) to to facilitate breast &
lower blood glucose. uterine function.
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Hypothalamic-Pituitary-
Axis regulates
hormone release
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Roadmap
1. The basics of hormone signaling
2. Female & Male Sex Hormones
3. Clinical & Non-clinical Uses
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Sex hormones
• Includes estrogens, progestins, and androgens
• Important for:
• Conception
• Sexual behavior/development
• Others
Sex hormone synthesis
• Estrogens
• Principal circulating estrogen:
Estradiol
• Progestins
• Principal circulating progestin:
Progesterone
• Androgens
• Principal circulating androgens:
Testosterone and DHT
Sex hormone regulation
Hormone feeds back
Hypothalamic-Pituitary-Gonadal Axis and turns on/off circuit…
Hypothalamus
+/-
Gonadotropin releasing hormone
(GnRH)
Pituitary Gland
+/-
Luteinizing hormone (LH),
Follicle-stimulating hormone (FSH)
Ovaries or Testes
Estrogen, progesterone, testosterone
Target Tissues
Sex hormone
effects:
Estrogen
Sex hormone
effects:
Testosterone
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Roadmap
1. The basics of hormone signaling
2. Female & Male Sex Hormones
3. Clinical & Non-clinical Uses
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Clinical & Non-clinical Uses
• Estrogens & Progesterone:
1. Hormonal contraceptives
2. Fertility enhancement
3. Hormone replacement therapy
4. Adjunctive therapy for some cancers
• Testosterone:
1. Hormone replacement therapy
2. Anabolic actions (stimulates protein synthesis)
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Ovulation Overview “LH Surge”
triggers ovulation
• Ovulation: hormone changes
trigger ovaries to release an egg
• Estradiol feeds back and turns
off GnRH, reducing LH &FSH
levels
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Knowledge Check
What would happen if you prevented the LH & FSH surge?
A. Ovulation would not occur.
B. Fertilization could not occur.
C. Pregnancy could not occur.
D. All of the above
E. None of the above
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Hormonal Contraceptives
• Goal: prevent pregnancy
• Approach: deliver estrogen
and/or progestin hormones to
prevent ovulation
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Hormonal Contraceptives
Estradiol and/or
Mechanism of Action progestins feeds back
and turns off circuit…
Hypothalamus
-
• Provides hormones to GnRH
provoke negative
feedback in axis Pituitary Gland
-
LH & FSH
• No hormone surges to
trigger ovulation Ovaries or Testes
Estrogen, progesterone
Target Tissues
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Hormonal Contraceptives
Mechanism of Action
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Hormonal Contraceptives
Mechanism of Action
• Target: estrogen and progesterone
receptors (nuclear receptors).
• Cellular Action:
1. Activates receptors inside target tissues
(agonist action)
2. Alters transcription of target genes
3. Mimics effects of endogenous hormones
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Are hormonal
contraceptives
effective?
(Handbook of Nonprescription Drugs, 18th ed.)
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But adverse effects exist for some patients…
Older women, smokers,
• Increased risk of thromboembolism family history, genetic
propensity
in select patients
• Lifetime risk of breast cancer not
changed
(Burkman et.al., 2004)
(Burkman et.al., 2004)
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Hormonal Contraceptives
Other Adverse Effects & Issues
• Depression
• Breakthrough bleeding
• Nausea
• Headache
• Skin pigmentation
• Drug-drug interactions
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Knowledge Check
CYP450s metabolize hormonal contraceptives. Also, some drugs
increase CYP450 activity (antibiotics, St. John’s Wort). If a patient
takes an antibiotic with an oral contraceptive, drug hormone levels will:
A. Increase
B. Decrease
C. Not change
