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Understanding Hormonal Contraception

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Understanding Hormonal Contraception Understanding Hormonal Contraception Alexandra Hall MD University of Wisconsin, Stout ACHA 2013 Disclosures • I will discuss off-label use of medications. • I have no financial conflicts of interest. Overview • Mechanisms of Action • Risks & benefits, based on pharmacology & physiologic effects • Safe prescribing, weighing the options Abbreviations • CHC = Combined Hormonal Contraceptive • Estrogen + Progestin • Pills, Patch, & Ring • BC = Birth Control • OC = Oral Contraceptive (COC=Combined Oral Contraceptive) • POP = Progestin-Only Pills, a.k.a. Mini-Pills • LNG-IUS = Levonorgestrel Intrauterine System (Mirena IUD) • DMPA = Depot-medroxyprogesterone acetate (Depo-Provera) • EE = Ethinyl estradiol • SHBG = sex hormone binding globulin • MEC = Medical Eligibility Criteria U.S. MEC www.cdc.gov/reproductivehealth/UnintendedPregnancy/USMEC.htm Resources • Hatcher et al., Contraceptive Technology • Dickey, Managing Contraceptive Pill / Drug Patients • Speroff & Fritz, Clinical Gynecologic Endocrinology and Infertility • Speroff & Darney, A Clinical Guide for Contraception • Association of Reproductive Health Professionals www.arhp.org • Free webinars • Free online resources • Free patient resources • Members get free subscription to journal Contraception LET’S GET STARTED! Case Astara believes strongly in using only natural products and doesn’t want to use anything synthetic. She wonders if there is an all-natural hormonal contraceptive available to her. What do you tell her? a. The hormones in OC’s are identical to the hormones her body normally makes. b. The hormones in a new pill named Natazia are bioidentical to natural hormones. c. The estrogen component of CHC is extracted from horse urine. d. The progestin component of CHC is extracted from yams. e. None of the above. WHAT IS CONTRACEPTION MADE OF? In the beginning… 80,000 sow ovaries = 5 gallons syrup Mexican yams = 12 mg estradiol & 3 kg progesterone 40 mg progesterone via chemical processes called the Marker Degradation Estradiol vs. Ethinyl Estradiol Estradiol Ethinyl Estradiol Our body’s natural estrogen. More lipophilic and more orally Not very bioavailable when bioavailable. Also much more potent taken orally. Also not easy to at estrogen receptors than estradiol, produce in large quantities. facilitating lower doses. This is the estrogen in almost all CHCs. Also more lipophilic and more orally Estradiol Valerate bioavailable. Used in Natazia. Synthetic hormones • Ethinyl estradiol is called an estrogen because it binds to estrogen receptors • There are multiple types of estrogen receptors • Different tissues express different types • Synthetic progestins are called progestins because they bind to progesterone receptors • Again, there are different types of receptors, expressed differently in different tissues • Most synthetic progestins, because they share a great deal of structural similarity with testosterone, will also bind to and activate testosterone receptors, called ‘androgenic activity.’ Due to other actions of CHCs, however, the net impact is overall anti- androgenic. • Drospirenone, however, is more similar to spironolactone, and will oppose testosterone action. 3 mg of drospirenone has approximately the equivalent anti-androgenic potency of 25 mg of spironolactone. Case Astara believes strongly in using only natural products and doesn’t want to use anything synthetic. She wonders if there is an all-natural hormonal contraceptive available to her. What do you tell her? a. The hormones in OC’s are identical to the hormones her body normally makes. b. The hormones in a new pill named Natazia are bioidentical to natural hormones. c. The estrogen component of CHC is extracted from horse urine. d. The progestin component of CHC is extracted from yams. e. None of the above. Case Tina is sexually active and desires birth control, but she is very strongly anti-abortion. She has heard that pills prevent a fertilized egg from implanting and thus could be considered abortive agents. What do you tell her? a. She is correct and should therefore use condoms. b. The primary mechanism of action for CHC is prevention of follicle development. c. The primary mechanism of action of progestin-only pills is prevention of ovulation. d. All hormonal contraceptives cause some atrophy of the endometrium, but it is not the main mechanism of action for any of them. e. None of the above. MECHANISM OF ACTION http://rhapsodyinj.tumblr.com/post/1592372482/i-recently-found-out-that-some-people-do-not From Jackie, “Lets Be Honest” Mechanisms of action of CHCs Ethinyl estradiol Progestin • Suppresses FSH/follicular • Suppresses LH/ovulation development • Dose-dependent • Less so in lower dose pills • Atrophies endometrium • Stabilizes endometrium and controls bleeding • Thickens cervical mucous • Potentiates the action of • Disrupts fallopian tube progestins, likely by secretion and peristalsis increasing intracellular • Is the main contraceptive progestin receptors ingredient. • Contributes very little to contraceptive efficacy. Mechanism of Action - DMPA • High levels of circulating progestin • Completely blocks LH, prevents ovulation • Thickens cervical mucous • Alters the endometrium • Suppresses FSH, although less so than estrogen • No replacement estrogen so overall E levels may be lower • Decline in bone mineral density Mechanism of Action - POPs • POPs have a lower amount of progestin in them than CHCs, only about 25% of the CHC dose • LH/ovulation are less reliably suppressed • 40% of women on POPs ovulate normally • Rely on cervical mucous changes • Occur about 2-4 hours after dose is taken • Effect diminishes at 22 hours, is virtually nonexistent at 24 hours • Must be taken daily at exactly the same time • If more than 3 hours late, need to use a back-up method x 48 hrs • Higher rates of irregular menstrual bleeding • 40-50% of women will have normal cycles • 40% have short, irregular cycles • 10% have no cycles – spotting, irregular bleeding, or amenorrhea Mechanism – Implant and IUS • Some suppression of LH/ovulation • Implant blocks ovulation for first 2.5 years but maintains efficacy for 3 • LNG-IUS - 85% of women are ovulatory after the first year • Thickening of cervical mucous • Atrophy of endometrium • LNG-IUS - Up to 90% decrease in menstrual bleeding, >50% amenorrheic at one year • Implant – 21% amenorrheic at 1 yr, 30-40% thereafter, but 20% with frequent or prolonged bleeding • No suppression of FSH or endogenous estrogen • No decrease in bone mineral density Case - answer Tina is sexually active and does not want to get pregnant, but is very strongly anti-abortion. She has heard that birth control pills prevent a fertilized egg from implanting and thus could be considered abortive agents. What do you tell her? a. She is correct and should therefore use condoms. b. The primary mechanism of action for CHC is prevention of follicle development. c. The primary mechanism of action of progestin-only pills is prevention of ovulation. d. All hormonal contraceptives cause some atrophy of the endometrium, but it is not the main mechanism of action for any of them. e. None of the above. Case Samantha has a history of morbid obesity treated with a laparoscopic gastric band three years ago. She is taking doxycycline for her acne. What do you tell her about her contraceptive options? a. Due to her surgery, she may not reliably absorb oral methods, so she should choose the patch, ring, injection, implant, or IUD. b. Due to an interaction with her doxycycline, she should avoid oral methods. c. She may use any method she wishes. d. She would do fine on any method except POP, as they are orally absorbed and such a low dose. ABSORPTION & METABOLISM Non-oral Methods • Patch, Ring, Injection, Implant, IUS • Direct absorption through tissues and into the systemic circulation OCs : Absorption from intestines Need intact, functional intestines CHCs POPs Intestinal Absorption: Vomiting & Diarrhea • May result in decreased absorption of OC’s and therefore decreased effectiveness • Options: • Use back-up method until on the pill again for a week • Insert pill vaginally* * Ziaei, Contraception 2002. Souka, Contraception 1986. Coutinho, Fertil Steril 1982 Enterohepatic circulation of EE 40% of dose enters blood • Conjugates of ethinyl estradiol are secreted in the bile • In the colon, bacteria break them apart • Free ethinyl estradiol is then reabsorbed • This results in a second round of EE absorption • This applies only to EE, not to progestins Enterohepatic circulation & Antibiotics • Antibiotic use can decrease colonic bacteria, thereby decreasing the amount of free ethinyl estradiol available for reabsorption • This resulted in warnings to pill users that all antibiotics could decrease contraceptive efficacy • Excellent studies have demonstrated that this potential interference DOES NOT occur in any clinically significant way; serum levels are unchanged, there is no increase in ovulation, and there is no decrease in effectiveness CHCs POPs Case Samantha has a history of morbid obesity treated with a laparoscopic gastric band three years ago. She is taking doxycycline for her acne. What do you tell her about her contraceptive options? a. Due to her surgery, she may not reliably absorb oral methods, so she should choose the patch, ring, injection, implant, or IUD. b. Due to an interaction with her doxycycline, she should avoid oral methods. c. She may use any method she wishes. d. She would do fine on any method except POP, as they are orally absorbed and such a low dose. Case Elizabeth
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