Pharmacology of the Reproductive System Notes

Introduction

• Overview of the pharmacology of the reproductive system, focusing on the roles of hormones and their therapeutic applications.

Female Hormones

• Estrogens and Progesterone are the main hormones discussed in relation to the female reproductive system.

Hormonal Regulation

• GnRH (Gonadotropin-Releasing Hormone) is secreted by the hypothalamus, stimulating the adenohypophysis to release FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone).

• Hormonal levels vary during the cycle:- Days 1-12: FSH increases, leading to follicular development.

  • Day 13-28: Peak in estrogen and progesterone triggers ovulation.

Natural Estrogens

• E2 (Estradiol): The most potent estrogen, synthesized from testosterone.

• E1 (Estrone): Considered the standard for estrogens, weaker than estradiol.

• E3 (Estriol): Weaker than estrone; significant during pregnancy.

• E4 (Estetrol): Produced only by the fetal liver during pregnancy.

Effects of Natural Estrogens

• Morphogenic effects on reproductive organs and maintenance of sexual characteristics.

• Regulate skeletal morphogenesis and endometrium maturation.

• Influence menstruation via estrogen/progesterone balance.

Physiological Effects

• Increased capillary permeability and positive hydroelektrolytic balance.

• Altered plasma lipoprotein profiles (increased HDL, decreased LDL).

• Enhance coagulation factor synthesis, affecting clotting properties.

Hormonal Interactions

• Synergistic effect with progesterone:- Small doses stimulate GnRH and pituitary gonadotropins; high doses inhibit.

Side Effects (SE) of Estrogens

• Potential side effects include nausea, nausea, hypertension, and risks of thromboembolic disorders.

Mechanism of Action (MoA)

• Estrogens enter cells and bind to intracellular receptors, forming a receptor complex that affects gene transcription across various tissues, including the uterus, vagina, and bones.

Therapeutic Indications for Estrogens

• Treatment of ovarian failure, amenorrhea, dysmenorrhea, and osteoporosis in menopause. Estrogens can also be used in prostate cancer.

• Contraindications include breast cancer, history of thrombosis, and pregnancy complications.

Estrogen Types

• Natural: Estradiol, Estrone, Estriol.

• Synthetic: Ethinylestradiol, Diethylstilbestrol.

Overview of Progesterone

• Key natural hormone involved in the reproductive cycle, secreted by ovaries and placenta.

Role of Progesterone

• Crucial for ovum implantation and maintaining pregnancy.

• Converts proliferative endometrium into secretory endometrium.

Indications and Side Effects of Progesterone

• Used for imminent abortion, ovarian hypofunction, and treatment of endometrial cancer.

• Side effects may include edema and potential virilization of female fetuses when administered in pregnancy.

Progestatives

• With androgenic effect: Lynestrenol, Norgestrel.

• Without androgenic effect: Didrogestone, Medroxyprogesterone. Mifepristone as an anti-progestin.

Selective Estrogen Receptor Modulators (SERMs)

• Medications like clomiphene, tamoxifen, and raloxifene that act as receptor modulators.

Clomiphene

• Partial agonist inducing ovulation by increasing GnRH secretion.

Tamoxifen and Toremifene

• Act as antagonists in breast cancer therapy by inhibiting endogenous estrogen.

Hormonal Contraception

1. Estroprogestative combinations.

2. Progestative-only contraceptives (minipills).

3. Emergency contraception with high doses of progestin.

Other Contraceptive Methods

• IUDs, subdermal implants, injectables, vaginal rings, and transdermal patches with varying duration and efficacy.

Side Effects of Hormonal Contraceptives

• DVT risk, breakthrough bleeding, and increased cancer risks.

Gonadorelin Analogues

• Triptorelin, Goserelin, Leuprolide — used in various malignant diseases and therapeutic conditions.

Early Puberty and Gonadotropins

• Characteristics of precocious puberty and hormonal involvement.

Gonadotropins Overview

• Hormones such as hCG and FSH with varied medical uses including ovulation induction.

Uterine Stimulation

• Induction of labour, therapeutic abortion, and management of postpartum hemorrhage with specific medications.

Uterine Stimulation Drugs

• Oxytocin, Ergometrine, and Prostaglandins — used in various scenarios of labor and delivery.

Uterine Relaxation Agents

• Beta2 agonists and others used to prevent premature labor.

Pharmacotherapy of Osteoporosis

• Introduction to osteoporosis and its implications.

Epidemiology and Definition of Osteoporosis

• A silent disease characterized by fractures and age-related risk factors.

Osteoclasts and Osteoblasts

• Definitions and roles of key bone cells involved in bone remodeling.

Postmenopausal Bone Imbalance

• Imbalance between bone formation and destruction.

Prevention of Osteoporosis

• Diet, calcium, and vitamin D recommendations.

Risk Factors for Osteoporosis

• Lifestyle factors such as alcohol use, immobility, and nutritional deficiencies.

WHO Classification of Osteoporosis

• Based on BMD (Bone Mineral Density) and T-scores.

Universal Recommendations for Osteoporosis

• Counseling, diet, exercise, and fall prevention strategies.

Influencing Factors for Bone Health

• Nutritional and hormonal influences affecting bone metabolism.

Bone Physiology

• Details about bone cells and structure.

Calcium Regulation

• Mechanisms involving PTH and calcitonin in maintaining calcium homeostasis.

Clinical Signs

• Chvostek's and Trousseau's signs indicative of low calcium levels.

Physiological Importance of Calcium

• Calcium functions beyond bone health, impacting multiple body systems.

Bone Remodeling

• Introduction of osteoclasts and osteoblasts in bone homeostasis.

Calcitonin and PTH Roles

• Regulation of calcium levels in the blood and their physiological feedback mechanisms.

Vitamin D and Its Pathways

• Conversion of Vitamin D and its critical roles in calcium absorption.

Osteoporosis Classification

• Types of osteoporosis and their characteristics.

Therapy for Osteoporosis

• Overview of FDA-approved drugs, including bisphosphonates and others.

Vitamin D Homeostasis

• Roles in calcium health and associated physiological pathways.

Calcitonin Overview

• Formulations and their uses in treating osteoporosis.

Role of Estrogens in Osteoporosis

• Estrogens and their protective effects against bone loss.

Estrogen Receptor Interactions

• Mechanisms of estrogen regulation in bone health.

Different Types of Estrogens

• Classes of estrogens including synthetic and tissue-selective agents.

Raloxifene as a SERM

• Unique properties of Raloxifene as a selective estrogen receptor modulator.

Bisphosphonates

• Mechanism and effects on osteoclast behavior in bone remodeling.

Bisphosphonate Pharmacokinetics

• Insights into absorption, metabolism, and side effects of bisphosphonates.

Relative Potency of Bisphosphonates

• Potency rankings of various bisphosphonates used in clinical settings.

Denosumab Overview

• Mechanism of action and clinical usage in osteoporosis treatment.

Parathyroid Hormone (PTH) Agents

• Use and efficacy in stimulating bone formation and managing osteoporosis.

Strontium Ranelate

• Unique dual action on bone metabolism and its pharmacokinetics.

Bisphosphonates and Statins Interaction

• The relationship between statins and bone metabolism.

Male Hormones Overview

• Focus on androgens as key male sex hormones.

Definition of Androgens

• Their primary roles in male development and body composition.

Androgen Biosynthesis

• Hormonal pathways involved in testosterone production.

Characteristics of Natural Androgens

• Details on testosterone and its metabolism in the body.

Testosterone Secretion

• Mechanisms and effects of testosterone production during puberty.

Androgen Effects

• Distinction between anabolic and androgenic effects of testosterone.

Anabolic Effects of Androgens

• Overview of protein synthesis stimulation and muscle growth.

Anabolic Index

• Definitions and examples of anabolic steroids and their ratios.

Virilizing Actions of Androgens

• The role of androgens in male sexual characteristics and reproductive function.

Anabolic Actions

• Effects on muscle and bone, counteracting glucocorticoids.

Metabolic Effects of Androgens

• Influence on metabolism, fat deposition, and calcium absorption.

Other Physiological Effects

• Overview of androgens on bodily functions and metabolism.

Mechanism of Action

• Interaction of androgens with nuclear receptors and related conditions.

Clinical Indications for Androgens

• Indications for both male and female patients, and related conditions.

Precautions and Side Effects

• Common side effects and contraindications associated with androgens.

Pharmacokinetics of Androgens

• Absorption and distribution patterns for different administration methods.

Virilizing Androgens

• Practical application and considerations for testosterone therapies.

Anabolizing Steroids

• Their role in muscle regeneration, effects on appetite, and potential uses in specific cases.

Anabolizing Steroid Effects

• Side effects and concerns around their use, particularly in young populations.

Clinical Indications for Anabolic Steroids

• Use cases in medical treatments and dietary needs.

Hormonal Antagonists

• Antiandrogens used in prostate cancer and other cases, along with their effects.

Conclusion

• Summary of the key themes of pharmacology relating to the reproductive system and hormones.