PC1320 W3 Lecture 3b_Pharmacology of_Reproductive Hormones
Page 3: Learning Outcomes
Demonstrate understanding of:
GnRH (Gonadotropin-releasing hormone) from the hypothalamus
FSH (Follicle-stimulating hormone) and LH (Luteinizing hormone) from the anterior pituitary
Testosterone, estrogen, and progesterone from gonads
Effects of Reproductive Hormones:
Androgenic and anabolic effects
Endogenous testosterone and therapeutic uses of synthetic analogues, including toxicities
Application of synthetic estrogen and progesterone in contraception and hormone replacement therapy (HRT)
Page 5: Gonadal Hormones
Primary Female Sex Hormones: Estrogen and Progesterone
Primary Male Sex Hormone: Testosterone
Hormonal Presence: Women produce small amounts of testosterone; men produce small amounts of estrogen and progesterone
Page 6: Testosterone
Production: Primarily in testes; minimal from adrenal glands
Functions:
Influences puberty, size of penis and testes, body hair, sex drive, sperm production, fat distribution, red cell production, and maintenance of muscle strength
Body Impact: Affects heart, brain, bones, liver, kidneys, skin
Low Testosterone Symptoms:
Decreased mood and energy, muscle mass/strength loss, decreased facial/body hair, erectile dysfunction, loss of sex drive, anemia
Page 7: Estrogen and Progesterone
Estrogen: Main female hormone produced from ovaries, adrenal glands, and fat cells
Affects sexual development, reproductive health, brain, cardiovascular system, etc.
Life Stages Affected: Puberty, menstruation, pregnancy, menopause
Progesterone: Prepares uterine lining for fertilization, supports pregnancy, suppresses estrogen after ovulation
Page 8: Gonads & Gonadal Hormones
Processes Involved:
Male Gonads: Testis, involves Sertoli cells for gametogenesis, GnRH influences FSH, LH leading to testosterone production
Female Gonads: Ovaries produce estrogens and progesterone during reproductive processes
Gonadal hormones regulate secondary sex organs and reproductive tract tissues
Page 9: Biosynthesis of Gonadal Hormones
Starting Point: Cholesterol biosynthesis of steroids
Key hormones include Progesterone, Testosterone, Estrogens via distinct pathways like 5-alpha-reductase and aromatase
Differences: Quantitative variations between sexes, but qualitative similarities
Page 10: Mechanism of Action of Testosterone
Conversion: Testosterone to dihydrotestosterone (DHT) via 5-alpha-reductase
Testosterone interacts with nuclear receptors to affect gene transcription
DHT is the active form in many tissues, showing higher receptor affinity
Page 11: Circulating Levels of Hormones
In Utero:
Hormonal levels determine sex differentiation starting at >6 weeks
Lack of testosterone can result in microphallus and cryptorchidism
At Puberty:
Surge in GnRH, LH, FSH, testosterone leading to secondary sex characteristics development; anabolic effects on skeletal/muscle growth
Behavioral and psychological impacts often seen (increased physical vigor, libido, aggression)
Page 12: Bone & Spermatogenesis Effects
Oestrogen Deficiency:
Impacts growth spurts, epiphyseal closure, skeletal maturation, and testosterone feedback
Potential effects: infertility, delayed maturation, and changes in sexual development
Page 13: Estrogen Deficiency in Men
Illustration: Man with aromatase deficiency showing signs like genu valgum, affecting body anatomy/function
Page 14: Testosterone Deficiency
Consequences:
Leads to infertility and excess testosterone can inhibit LH & FSH, leading to testicular atrophy
Relevant hormones involved: Spermatozoa, Leydig cells
Page 15: Therapeutic Uses of Testosterone
Forms: Rapidly metabolized; non-orally active, but as testosterone undecanoate, it can be administered via various routes
Uses:
Hypogonadism, delayed puberty, impotence, reversing muscle loss due to disease
Page 16: Antiandrogens
Cyproterone Acetate:
Androgen receptor antagonist, uses include treatment of masculinization in females, libido suppression in males, and prostate cancer
Finasteride:
Inhibits 5-alpha-reductase; used for benign prostatic hyperplasia and androgenic alopecia
Page 17: Gonadal Hormones in Females
Mechanism of Action:
Estrogen binds to nuclear receptors, leading to genomic effects
Critical for development of secondary sex characteristics and menstrual cycle regulation
Page 18: Oestrogen Effects
Sources: Ovarian follicular cells and placenta during pregnancy
Influences reproductive tissue maintenance, acts on endometrium, and increases HDL
Page 19: Pharmacy Preparations
Forms of Oestrogens: Available in various dosage forms including oral, transdermal, and implantable
Includes both natural and synthetic oestrogens for various indications
Page 20: Oestradiol Effects
Oral Activity: Inactive orally except for 17-ethinyl oestradiol
Functions in female sex characteristics, metabolic actions, and blood coagulability
Risks associated with increased thromboembolism
Page 21: Therapeutic Uses of Oestradiol
Applications:
Hypogonadism, hormone replacement therapy, and contraception
Uses in cancer treatment and inducing ovulation
Page 22: Risks Associated with Oestradiol Use
Major Concerns:
Increased risk of endometrial carcinoma, breast cancer, and metabolic/gastrointestinal effects
Cardiovascular risks such as thromboembolism
Page 23: Progesterone Functions
Production: From corpus luteum/placenta
Prepares uterus for implantation, cervical mucus changes, and influences body temperature
Page 24: Progestogen Activity
Orally Active:
Example: Norethindrone, enables effective contraception
Mechanism of action through nuclear receptor alterations
Page 25: Roles of Progestogens
Clinical Uses:
Contraception, hormone replacement, and treating endometriosis
Support roles in pregnancy and cytogenesis
Page 26: Anti-progestogens (Mifepristone)
Mechanism: Breaks down uterine lining to terminate early pregnancy
Used with PGE derivatives to enhance effectiveness
Adverse effects include gastrointestinal discomfort and prolonged bleeding
Page 27: Contraceptive Mechanisms
Oestrogen: Inhibits FSH release, thus follicle development
Progestogen: Prevents LH surges and thins endometrium, blocking implantation
Page 28: References Used
Multiple pharmacology textbooks and Australian Medicines Handbook 2024 for study references.
Page 29: Practice Questions
Discuss the anabolic steroids and associated health risks for males and females.
Describe mechanisms of action, clinical uses, and adverse effects of reproductive hormones and associated agents.