Estrogens and Progestins

estrogens & progestinsFebruary 4, 2014Sarah Adkins, PharmD, BCACP

OutlinePharmacology basics of estrogens and progestinsPharmacology and therapeuticsContraceptionMOA (mechanism of action)AdministrationSide effects Drug interactionsHormone replacementOtherClinical pearls

PharmacologyPharmacology: estrogensNatural estrogens Estradiol (Estrace)sourcebioavailabilityConjugated estrogens (Premarin)sourcebioavailability

Estradiol is our natural estrogen. Its derived form a Soy source if needed. But our bodies make this stuff.

Conjugated estrogens made from pregnant horse urine.

The bioavailability of these two is about the same. 4Pharmacology: estrogensSynthetic estrogensSteroidalEthinyl estradiol (EE)Mestranol

Non-steroidalDiethylstilbestrol

http://www.cancer.gov/cancertopics/factsheet/Risk/DES Derived form normal estrogens. EE is everywhere. EE is in almost every contraceptive. Mestranol turns to EE in the blood.

DONT KNOW ABOUT ONE ON THE BOTTOM5Pharmacology: progestinsNatural progestinProgesterone (Prometrium, Crinone gel)source PEANUT ALLERGY WITH PROMETRIUM

Its made with peanut oil. REMEMBER THIS.

This drug is used for menopause. 6

Pharmacology: progestinsSynthetic progestins

DesogestrelDienogestDrospirenoneEthynodiol diacetate Levonorgestrel

Medroxyprogesterone acetate Norethindrone acetateNorgestimate NorgestrelUlipristal mini pill. Progestin only.

Progestins in many types of birth controls. They have androgenic effects. The androgenic effects vary.

Drospirenone potassium sparring diuretic. Concern if they are on ACE inhibitor. 8Pharmacology & TherapeuticsContraception: MOAInhibition of pituitary gonadotropin release (FSH & LH); involving both decreased release of GnRH & decreased pituitary responsivenessInhibition of ovulation (mid-cycle surge of LH is absent)Other mechanisms: such as changes in cervical mucus (making it less permeable to sperm) & altered fallopian tube motility may also play a role

Normal Menstrual Cyclecontraception effectsHypothalamusGnRHFSH, LH(-)Pharmacologic amounts of estrogens; pharmacologic amounts of progestinsDecreased release of GnRHDecreased pituitary responsivenessto GnRH & thus decreased release of FSH & LHAnterior lobePosterior lobeFSH, LHPharmacologic amounts of estrogens; pharmacologic amounts of progestins(-)Combination Oral ContraceptivesPituitary0ContraceptionOralTopical (patch)InjectionSubcutaneousSubdermal implantVaginalIUS (Intrauterine system)

13Contraception: oral Low dose monophasicHigh dose monophasicBiphasicTriphasic Four phasicExtended cycle Continuous cycle Emergency contraception

14Contraception: oralEmergency contraceptionLevonorgestrel Two dose regimen:one 0.75 mg as soon as possible within 72 hours of unprotected sexual intercourse; a second 0.75 mg tablet should be taken 12 hours after the first doseSingle dose regimenone 1.5 mg tablet as soon as possible within 72 hours of unprotected sexual intercourse

Its a progestin. 15Contraception: oral Progestin only mini-pill MOA of progestin only

When do you give a mini pill? When someone is breast feeding where you can not have estrogens. 16HypothalamusGnRHFSH, LH(-)Pharmacologic amounts of progestinsDecreased release of GnRHDecreased pituitary responsivenessto GnRH & thus decreased release of FSH & LHAnterior lobePosterior lobeFSH, LHPharmacologic amounts of progestin(-)Progestin-only Oral ContraceptivesPituitary0Not quite the potency. 17Contraception: non-oralTopical (patch)Ortho Evra (EE 35mcg/day & norelgestromin, active form of norgestimate, 200mcg/day)weekly x 3 weeks and 4th week is patch freeInjectionDepo Provera IM (medroxyprogesterone acetate 150mg)every 3 monthsSubcutaneousDepo subQ Provera (medroxyprogesterone acetate 150mg)every 3 months

These are expensive. 18Contraception: non-oralSubdermal implantNexplanon (etonogestrel, release varies over time) 3 yearsVaginalNuvaRing (EE 15 mcg/day & etonogestrel 0.12 mg/day)vaginal ring inserted for 3 weeks and removed for 1 weekIUS (Intrauterine system)Mirena (Levonorgestrel 20mcg/day) up to 5 yearsSkyla (Levonorgestrel 14 mcg/day) up to 3 years

Contraceptives: side effects

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22Contraceptives: other adverse effects Concerns related to significant adverse effectsCarbohydrate intolerance (diabetes)Lipid effectsDepressionGall bladder diseaseMigraine (some have low does estrogen in the pill to prevent the headaches)Renal impairmentContraception: contraindicationsBreast cancer or other estrogen/progestin related neoplasmIn women with high risk of arterial or venous thrombotic disease > 35 years of age who smoke (US Boxed Warning)Hepatic tumors or diseasePregnancyUndiagnosed abdominal uterine bleeding

Contraception: drug interactionsAvoid concomitant useAnastrozole (used to block estrogens in women with breast cancer.Thyroid replacement medicationsHerbal supplementsMifepristoneAnticoagulants Lamotrigine (Lamictal)Bile acid sequestrants (cholestyramine resin, Questran)Phenytoin (Dilantin)

25Case #1aA 14 year old, Emily Jones, comes to your office two weeks post-partum. She is limited in her resources. You: give her a lecture about safe sex and contraceptioncomplete her physical exam and ask how she is feelingprescribe Lo/Ovral-28 (EE 30mg/Norgestrel 0.3mg) prescribe NuvaRing (EE 15mcg/day & Etonogestrel 0.12mg/day)do not prescribe anything and schedule a follow up

None of these are wrong. Ask her if she is breastfeeding.

Can prescribe EE if she is not breastfeeding. 26Case #1bYou have a nice discussion with Ms. Jones about birth control, breast feeding and post-partum depression. Ms. Jones has decided that she will begin using birth control. Which of the options below may be the best for Ms. Jones? Jolivette (Norethindrone 0.35mg only) LoSeasonique (Extended cycle, EE 20mcg & levonorgestrel 0.1mg x 84 days)Depo-Provera Inj. (Medroxyprogesterone acetate 150mg x 3 months)Mirena IUS (Levonorgestrel 20mcg/day for up to 5 years)

She is not responsible. 27Case #2a25 year old, Stacey Smith, visits you at the clinic and would like to start birth control. She has never used hormone contraceptives. She and her partner are currently using condoms and spermicide. She is a little nervous and would like to take something that is similar to her normal cycle. What might be a good starting contraceptive choice? Ortho Evra patches (EE & norelgestromin) apply for 3 weeks then off 1 weekDepo Provera IM (medroxyprogesterone) 150 mg every 3 monthsExtended cycle Seasonique (EE & levonorgestrel x 84 day)Progestin only (Norethindrone 0.35 mg daily)Lo/Ovral 28 (EE 30 mcg & norgestrel 0.3 mg) Bleed every 30 days28Case #2bMs. Smith returns to the clinic after 3 months on the medication. She is complaining of nausea, breast tenderness and weight gain. What might be the reason for these complaints? Has she been on it long enough? What options below might be appropriate for Ms. Smith? Ortho Cyclen 28 (EE 35 mcg & norgestimate 0.25 mg) Ovcon 50 (EE 50 mcg & norethindrone 1 mg) Jolivette (mini pill) (Norethindrone 0.35 mg) LoSeasonique (extended cycle, EE 20 mcg & levonorgestrel 0.1 mg x 84 days) Lessina (EE 20 mcg & levonorgestrel 0.1 mg) Too much estrogen is the problem.

Can do mini pill

Can do low sesoniqe. Can due lessina29Hormone replacementOral prescriptionherbal supplements (soy, black cohosh)Topicalpatches and gelsVaginal ringCompounded bio-identical hormones

NOTE: importance of tapering when discontinuingOther therapeutic usesOsteoporosisEndometriosisAndrogen dependent prostate cancer in menHypersexuality (medroxyprogesterone)

Clinical PearlsBreast cancerBlood clotsSmokingCostAdministrationAdherencePeanut allergy with Prometrium

Questions?

ResourcesWince L. Pharmacology of estrogens and progestins ppt. 29 Jan 2013. Steroidal estradiol image: Adapted from Katzungs Basic & Clinical Pharmacology, McGraw-Hill, 9th edition (2004).PL Detail-Document #290305. Chart: Comparison of Oral Contraceptives and Non-Oral Alternatives. The Pharmacists Letter/Prescribers Letter. Updated March 2013. [Accessed 2 Feb 2014] PL Detail-document # 280506. Chart: Postmenopausal Hormone Therapy. The Pharmacists Letter/Prescribers Letter. Updated May 2012. [Accessed 2 Feb 2014] Shrader S, Diaz V. Contraception. Chapter 88. Pharmacotherapy: a physiologic approach. 8th edition. Table 88-2 Adverse effects of combined hormonal contraception and their management. [accessed 2 Feb 2014]. Available at: http://accesspharmacy.mhmedical.com.proxy.lib.ohio-state.edu/content.aspx?bookid=462&sectionid=41100865 Drug information: Alesse, estradiol, . Lexicomp Drug Information Smartphone app. [Accessed 2 Feb 2014] Nilson J, Deng J, Brinton R. Impact of Clinically Relevant Progestins on the Neural Effects of Estradiol and the Signaling Pathways Involved. Drug News Perspect 2005, 18(9): 545, ISSN 0214-0934, Copyright 2005 Prous ScienceCCC: 0214-0934