Académique Documents
Professionnel Documents
Culture Documents
Hypothalamus GnRH Anterior Pituitary FSH and LH Ovary Estrogen and Progesterone
FEMALES
Reference: Hansen L, Gunning K. Disorders Related to the Menstrual Cycle. In: Koda-Kimble et al. Applied TherapeuJcs; The Clinical Use of Drugs, Ninth EdiJon. LippincoN Williams & Wilkins, 2009: 47-1 to 47-27.
2/24/12
Reference: Hansen L, Gunning K. Disorders Related to the Menstrual Cycle. In: Koda- Kimble et al. Applied TherapeuJcs; The Clinical Use of Drugs, Ninth EdiJon. LippincoN Williams & Wilkins, 2009: 47-1 to 47-27.
Follicular Phase
FSH stimulates a number of follicles (each containing
an ovum) begin to develop After 5 to 6 days, a dominant follicle forms The theca cells and granulosa cells of this dominant follicle multiply and synthesize and release estrogens. The estrogen inhibits FSH release and may cause regression of the immature follicles. Estrogen peaks just before midcycle and causes an LH and FSH surge. The LH surge leads to ovulation.
Chrousos G. The Gonadal Hormones & Inhibitors. In: Basic & Clinical Pharmacology. Editors: Betram G. Katzung, Susan B. Masters, Anthony J. Trevor, 11th edition. (2009) Mcgraw-Hill, New York, NY.
2/24/12
Luteal Phase The theca cells and granulosa cells form the corpus luteum. The corpus luteum produces estrogen and progesterone. If pregnancy does not occur, the corpus luteum degenerates and stops producing hormones. This decline in hormones leads to endometrium shedding.
Chrousos G. The Gonadal Hormones & Inhibitors. In: Basic & Clinical Pharmacology. Editors: Betram G. Katzung, Susan B. Masters, Anthony J. Trevor, 11th edition. (2009) Mcgraw-Hill, New York, NY.
Estrogens
Estradiol is the major secretory hormone of the
ovary Estrone and estriol are mostly formed in the liver or in the peripheral tissues
Necessary for: 1. Female Maturation 2. Endometrial lining 3. Metabolic and Cardiovascular Effects 4. Blood coagulation
2/24/12
Estrogens
Clinical
Uses:
2/24/12
FDA safety warnings on all estrogen: Can increase risk of MI, stroke, breast cancer, thromboembolism Dosing: Use the lowest dose for shortest amount of time
2/24/12
to give estrogen with a progestational agent if patient has uterus to protect against endometrial hyperplasia and endometrial cancer.
2/24/12
Progesterone
Necessary for: Maturation and shedding of the
endometrium lining
Levels
phase
Uses
Hormone replacement
ie. medroxyprogesterone
Hormonal contraception
ie. Depo-Provera, Micronor, Mirena Intrauterine Device
(IUD)
Hormonal Contraception
2/24/12
painful menstration (dysmenorrhea) Protection from endometrial cancer Protection from ovarian cancer and suppression of development of ovarian cysts Reduced risk of benign breast disease Decreased incidence of ectopic pregnancy Acne improvements
2/24/12
Disadvantages of CHC
Compliance No STD protection in VTE, stroke, MI TG Blood pressure benign hepatocellular adenomas breast cancer ? cervical cancer
Contraindications of CHCs
Many
contraindications
2/24/12
Common Complaints
Estrogen Excess
Progestin Excess
Progestin Deficiency
Late breakthrough bleeding Amenorrhea Hypermenorrhea
Estrogen Deficiency
Androgen excess
that induce Cyt P450 3A4 will increase metabolism and, therefore, decrease combined oral contraceptive efficacy Some antibiotics can kill GI bacteria, which decrease serum levels of estrogen by interfering with enterohepatic recirculation
10
2/24/12
Contraception:
Progesterone
Only Options
11
2/24/12
Depo-Provera (Medroxyprogesterone)
IM & SQ formulations (Depo-SubQ Provera) Q 3 month administration Advantages
- failure rate - or no menses - Every 3 months Disadvantages - Delayed return to fertility - If side effects occur, not able to discontinue immediately - Breakthrough bleeding - Weight gain - Office visits - May BMD
12
2/24/12
Products:
Take 1 tablet ASAP, then take the 2nd tablet 12 hours later
Plan B One-Step: 1 tablet of levonorgestrel 1.5 mg OTC status for women 17yo and older Prescription for those <17yo
Availability:
Sold behind the pharmacy counter Must have a pharmacist on duty and available for counseling when product is sold.
Mifepristone
Uses: Strong inhibitor of progesterone receptor Abortifacient Side effects: vomiting, diarrhea, abdominal pain,
13
2/24/12
Tamoxifen
MOA: competitive partial agonist inhibitor of estradiol Uses: Treatment and Prevention (in high risk women) of breast cancer May increase risk of endometrial cancer May increase risk of arterial and venous thromboembolism
Agonist=on lipid, bones, endometrium Antagonist=on breast tissue
Raloxifene
Uses: prevention of postmenopausal osteoporosis prophylaxis of breast cancer in women with risk factors MOA: May increase risk of arterial and venous thromboembolism
Agonist=on lipid and bone Antagonist= on the endometrium or breast tissue
Clomiphene
Ovulation-inducing
agent Partial estrogen agonist Inhibits estradiols negative feedback effect on the gonadotropins at the hypothalamus, leading to ovulation Will not help in patients with ovarian or pituitary failure Uses: Stimulate ovulation Adverse effects: hot flushes
14
2/24/12
Males
The
most important androgen secreted by the testis is testosterone. 65% of circulating testosterone is bound to sex hormone-binding globulin (SHBG) In many target tissues, testosterone is converted to dihydrotestosterone.
Testosterone
Some
Clinical Uses:
15
2/24/12
Testosterone Products
Buccal
Tablet= Striant Transdermal gels= Testim, Androgel Transdermal Patches= Androderm Injectables= Depo-Testosterone Oral products should not be used because can cause liver problems
Testosterone
Adverse
Effects:
deep voice In men=acne, sleep apnea, gynecomastia, erythrocytosis, azoospermia Sodium retention, edema (not common), hepatic dysfunction
16
2/24/12
5 reductase inhibitor
Finasteride
17
2/24/12
Receptor Inhibitors
Flutamide Inhibits binding of androgens at the receptor Used in treatment of prostate cancer Liver failure (black box warning) Bicalutamide (Casodex) and Nilutamide (Nilandron) Androgen receptor inhibitor Used for Prostate cancer Spironolactone Competitive inhibitor of aldosterone and competes with dihydrotestosterone for androgen receptors Treats hirsutism in women
References:
Chrousos G. The Gonadal Hormones & Inhibitors. In: Basic & Clinical Pharmacology. Editors: Betram G. Katzung, Susan B. Masters, Anthony J. Trevor, 11th edition. (2009) Mcgraw-Hill, New York, NY. Hardman JL. Contraception. In: Koda-Kimble MA, et al,eds. Applied Therapeutics: the clinical use of drugs. Ninth Edition. Lipppincott Williams & Wilkins. 2009:45-1 to 45-28. Dickerson LM, Shrader SP, Diaz VA. Contraception. In: Dipiro, et al. Pharmacotherapy; a pathophysiolgical approach. Seventh Edition. The McGraw Hill Companies, Inc. 2008:1313-1343. Kalantaridou S, Davis S, Calis KA. In: Dipiro, et al. Pharmacotherapy; a pathophysiolgical approach. Seventh Edition. The McGraw Hill Companies, Inc. 2008:1351-1368. Hormonal contraception. Pharmacist's Letter/Prescriber's Letter 2007;23 (12):231207. (Update June 2010). Parent-Stevens L. The Transition Through Menopause. In: Koda-Kimble MA, et al,eds. Applied Therapeutics: the clinical use of drugs. Ninth Edition. Lipppincott Williams & Wilkins. 2009:48-1 to 48-9.
18