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

1. Discuss the anabolic steroids and associated health risks for males and females.

2. Describe mechanisms of action, clinical uses, and adverse effects of reproductive hormones and associated agents.