Pharmacology of Repro Hormones PDF

Pharmacology of Repro Hormones HPG Axis Hormone Agonists and Antagonists Hypothalamic Pituitary-Gonadal (HPG) Axis 3 parts: o Hypothalamus o Anterior Pituitary o Gonads Hypothalamus produces GnRH o Stimulates Anterior pituitary o Releases FSH/LH to gonads § Testosterone from testes § Estrogen from o...

Pharmacology of Repro Hormones HPG Axis Hormone Agonists and Antagonists Hypothalamic Pituitary-Gonadal (HPG) Axis 3 parts: o Hypothalamus o Anterior Pituitary o Gonads Hypothalamus produces GnRH o Stimulates Anterior pituitary o Releases FSH/LH to gonads § Testosterone from testes § Estrogen from ovaries o Secondary sex characteristics § Spermatogenesis § Folliculogenesis HPG Axis Hormone Agonists/Antagonist Drugs GnRH Analog Leuprolide Goserelin Histrelin GnRH Antagonist Degarelix Ganirelix Cetrorelix Gonadotropin Agonist Menotropin (mixed LH, FSH) Follitropin (FSH) Lutropin (LH) Testosterone Agonist Testosterone Antagonist Methyltestosterone Spironolactone Finasteride Abiratone Flutamide Ketoconazole Estrogen Agonists SERMs Aromatase Inhibitors Ethinyl Estradiol Raloxifene, Clomiphene, Tamoxifen Exemestane, Anastrazole, Letrozole Progestins Levonorgestrel Medroxyprogesterone Etonogestrel Norethindrone Megestrol Mifepristone Ulipristal LH/FSH Agonist Anti-progestins General Uses of HPG Axis Drugs Inappropriate tissue growth of Hormone Dependent Tissues o Benign Prostatic Hyperplasia (BPH) o Cancers o Endometriosis (Estrogen drives growth of endometrium) o Leiomyomas (Estrogen dependent) o Puberty suppression in precocious puberty and gender dysphoria Disruption of HPG Axis o PCOS- Polycystic ovarian syndrome o Prolactinomas Hormone Replacement o Menopause (menopausal symptoms) o Prevention of osteoporosis post menopause o Low testosterone o Hypogonadism Control of Ovulation o Ovulation stimulation (infertility treatment) o Contraception Gender-Affirming Hormone Therapy GnRH Agonist/Antagonist GnRH (gonadotropin-releasing HPG axis hormone) o Released or administered in a pulsatile fashion o GnRH will INCREASE LH and FSH o Continuous use: GnRH will DECREASE LH and FSH (after a few days-weeks of initial “flare” or increase in release) FSH and LH increase production of estrogen and testosterone o Testosterone: negative feedback on its own production o Estrogen: negative or positive feedback on its own production o Progesterone: negative feedback GnRH Analogs (Agonists) GnRH analogs: leuprolide, goserelin, histrelin Initial Flare-Up (short acting): Temporary increase FSH and LH Sustained Release formulas (GnRH antagonist) Inhibiting GnRH from hypothalamus o Suppresses LH and FSH o Leads to: decrease testosterone and estrogen Used for: o Prostate carcinoma o Advanced breast cancer o Endometriosis o Endometrium thinning (prior to ablation) o Surgical excision of leiomyoma o Early puberty (abnormal)- temporarily suppressing HPG axis o Delay puberty in gender dysphoric children Side effects: o Hypogonadism o Hot flashes o Erectile dysfunction o Decreased libido o Osteoporosis (long-term exposure) GnRH Antagonists No start-up flare Degarelix– prostate cancer Ganirelix, cetrorelix: ovulation induction to control IVF timing o Stop follicular rupture for harvest o Off-label for endometriosis, uterine fibroids, menorrhagia, gynecomastia Side effects: Hot flashes, liver toxicity Glycopeptide Hormones: LH, FSH, hCG Gonadotropins (and TSH) are glycopeptide hormones Heterodimers that contain identical α subunits and β subunits that confer biological specificity Gonadotropins synthesized by Gonadotrophs and Syncytiotrophoblast o Gonadotropes (anterior pituitary): LH, FSH o Syncytiotrophoblast of placenta: hCG (exogenous hCG is LH receptor agonist for infertility tx) TSH or thyroid-stimulating hormone LH/FSH Agonists cause Ovulation Induction Stimulation of Follicle Development (endogenous LH/FSH) Controlled Ovarian Stimulation (for successful pregnancy) Triggering Ovulation (triggered by hCG or GnRH agonist) LH/FSH agonists use in vitro fertilization (IVF) or intrauterine insemination (IUI) hCG is an LH receptor agonist Menotropin: Purified from the urine of menopausal women hMG (high LH/FSH) Follitropin: FSH from urine of menopausal women Lutropin (hCG): Recombinant LH Goal: gain control of ovulatory cycle to harvest multiple oocytes o GnRH agonist and antagonist suppress endogenous cycle o hMG stimulates follicular development, hCG or FSH stimulate ovulation Menotropin Fertility treatment Regulates Hormone Levels Ovarian Stimulation to produce multiple follicles Hormone Replacement Therapy: Stimulate growth and development of ovarian follicles Side effects: ovarian hyperstimulation syndrome o Ovarian Hyperstimulation Syndrome (OHSS) § Caused by stimulation of ovaries for infertility § Excessive stimulation of the ovaries →multiple ovarian follicles → large amounts of ovarian hormones § Bloating, weight gain § Ascites: Dyspnea (pleural effusion), oligura/anuria § Thromboembolism, sepsis, death