Pharmacology of Female Sex Hormones (PDF)

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Pharmacology of Natural and Synthetic Female (ovarian) Sex Hormones: Agonists and Inhibitors George Ainooson (PhD) Dept. of Pharmacology CHS,...

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Pharmacology of Natural and Synthetic Female (ovarian) Sex Hormones: Agonists and Inhibitors George Ainooson (PhD) Dept. of Pharmacology CHS, KNUST 1  Lecture Module description: This lecture will help students identify the actions, medical uses, and adverse reactions of natural and synthetic female (ovarian) sex hormone agonists and inhibitors. Exit Learning Outcomes/Objectives: At the end of the module, students will be able to: Describe the physiological effects of the major endogenous estrogens and progestogens. Give examples of clinically relevant natural and synthetic estrogens, progestogens and their respective inhibitors and describe their therapeutic uses and adverse reactions. www.knust.edu.gh 2 SEX HORMONES: The Hypothalamic-Pituitary-Endocrine Axis www.knust.edu.gh 3  Brainkart www.knust.edu.gh 4 SYNTHESIS: The Natural SEX HORMONES 5 ESTROGEN AND ANTI-ESTROGENS www.knust.edu.gh 6  Estrogen Some key effects of estrogen Inhibits gonadotropin secretion by pituitary Proliferation of uterus Lowers LDL and raises HDL Induces vasodilation Improves bone density – inhibits osteoclast and enhances osteoblast activity Promotes breast tissue proliferation www.knust.edu.gh 7 www.knust.edu.gh 8  Estrogens: Ethinyl estradiol Uses Adverse Effect of Estrogen Hormone replacement therapy (HRT) in Nausea, vomiting, headache postmenopausal women Breast discomfort Senile vaginitis: (oral /topical agents) Hypertension Delayed puberty in girls Endometriosis Dysmenorrhea: (they are used to induce Endometrial carcinoma anovulatory cycles when there is painful Deep vein Thrombosis (DVT) menstruation Acceleration of breast cancer Acne: Estrogen will inhibit androgen release by Early fusion of epiphyses in children the inhibition of the release of gonadotropin Benign hepatoma release from the pituitary Suppression of libido and induction of Dysfunctional uterine bleeding (progestin may be gynecomastia in men added as an adjunct) Prostate Cancer (palliative) www.knust.edu.gh 9  Anti-Estrogens: Clomiphene Citrate Action Block estrogen feedback inhibition of the Adverse Effect Multiple pregnancies, hypothalamus causing increased FSH and LH release Hot flashes that leads to enlargement of ovaries and induction of ovulation. Risk of ovarian tumour Hypertension Uses Endometriosis Induce ovulation in fertility treatment in females. Increased risk of endometrial Oligozoospermia in males carcinoma www.knust.edu.gh 10  Selective estrogen receptor modulators: Action Have both estrogenic and antiestrogen effects in a tissue-specific manner (Tamoxifen, Toremifene, Raloxifene). Tamoxifen Estrogenic effect; Agonist of the estrogen receptors on the uterus, pituitary, bone liver Antiestrogenic effect: Antagonist on estrogen receptors of the breast and blood vessels www.knust.edu.gh 11  Selective estrogen receptor modulators: Tamoxifen Uses Adverse Effect ER+ Breast Cancer in premenopausal Vomiting and postmenopausal women. Hot flashes Vaginal bleeding (endometrial Effective in male breast cancer. proliferation) DVT Risk of endometrial carcinoma www.knust.edu.gh 12 Selective estrogen receptor down regulators: Fulvestrant Action Adverse Effect Inhibits ER dimerization to suppress symptoms similar to menopause, such ER-induced nuclear activity. as hot flashes and mood changes. GIT effect: Nausea, vomiting, Uses diarrhea. In ER+ Breast Cancer in postmenopausal women who do not respond to tamoxifen www.knust.edu.gh 13  Aromatase Inhibitors Examples: Adverse Drug Reactions Letrozole, Anastrozole, Exemestane Hot flushes Nausea Action Diarrhoea Reversibly inhibit aromatization resulting in total Bone loss estrogen deprivation Thinning of hair Uses Early Breast cancer in postmenopausal women Advanced Breast cancer after tamoxifen failure www.knust.edu.gh 14 PROGESTERONE AND ANTI-PROGESTOGENS www.knust.edu.gh 15 16 Progesterone: Physiological Effects Thickens endometrium for implantation Supports pregnancy after implantation Breast engorgement Rise in Body Temperature Mood swings Oedema Irregular bleeding Low HDL levels Carbohydrate intolerance www.knust.edu.gh 17 www.knust.edu.gh 18 Progesterone receptor analogues C-21 Compounds Antiandrogen Pharmacology ic effect Weak antiovulatory action Clinical Uses As an adjuvant to C-19 compounds estrogen in HRT They have potent antiovulatory action, but the estranes have Threatened androgenic and anabolic action, while Gonanes have little or no abortion androgenic/anabolic action hence preferred. Endometriosis Clinical Uses 19 Mainly used for contraception  Selective Progesterone Receptor Modulators (SPRM) Mifepristone Clinical Uses Potent antiprogestational action Termination of pregnancy (up to 7 weeks) Antiglucocorticoid action Antiandrogenic action Can be used to induce labour (not very popular). Postcoital Contraceptive/emergency (with 72h of unprotected intercourse) Action Decreases follicular development and inhibits ovulation ADR Abdominal pain, fatigue, and Blocks progesterone support to the endometrium Vaginal bleeding/heavy bleeding leading to contractions and induction of Birth defects if the pregnancy doesn’t end. menstruation Dislodges the conceptus www.knust.edu.gh 20  Selective Progesterone Receptor Modulators (SPRM) Ulipristal Action ADR Suppresses LH surge to inhibit Headache ovulation Nausea Stomach pain Clinical Uses Unusual tiredness or weakness Emergency contraceptive www.knust.edu.gh 21  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana References/further reading Katzung's Basic & Clinical Pharmacology, Todd W. Vanderah, 16th Edition, 2023 Rang & Dale's Pharmacology - 10TH Edition(2024) Goodman and Gilman's ‘The Pharmacological Basis of Therapeutics’, 14th Edition (2022) Int. J. Mol. Sci. 2021, 22(20), 11039; https://doi.org/10.3390/ijms222011039 22