Transcript Oral Contraceptives: good, bad and controversial
Hormonal Contraceptives: Good, Bad and Controversial
Herbert L. Muncie, Jr., M.D.
Susie
15 year old female comes in to discuss contraception She is healthy but wanted to talk about starting birth control pills What questions need to be asked?
What issues need to be addressed before considering hormonal contraception
Oral contraceptives (OCPs)
Approximately 80% of women will use OCPs during their lifetime Success rate if instructions followed perfectly - 99.9% first year of use Any missed pills - success rate 95% Adolescent’s success rate - 85-90%
OCPs - Estrogens
Two in U.S. Ethinyl estradiol (EE) Mestranol of EE 50 µg converted to 40 µg
OCPs - Progesterones
Progesterone
• Ethynodiol diacetate • Norethindrone • Norethindrone acetate • Levonorgestrel (LNg) • Norgestrel • Desogestrel • Norgestimate
Classification
1 st Generation 2 nd Generation 3 rd Generation
Family
Estrane (short ½ life) Gonane (longer ½ life) Gonane
Progestins (family) & OCPs
Examples Demulen ® 1/35 Norinyl ® 1/35, Ovcon ® 35, Ortho Novum 1/35 ® Loestrin ® Alesse ® , Lybrel ® , Seasonale ® , Triphasil ® , Tri-Levlen ® Ovral ® , Lo-Ovral ® Desogen ® , Mircette ® , Ortho-Cept ® Ortho-Cyclen ® , Ortho Tri-Cyclen ® Ethynodiol diacetate Norethindrone Norethindrone acetate Levonorgestrel Norgestrel Desogestrel Norgestimate
Mechanisms of action
Estrogen component Inhibits ovulation by suppressing FSH & LH Alters secretions & cellular structure of endometrial lining Prevents implantation
Mechanisms of action
Progesterone component Inhibits ovulation by suppressing LH Thickens cervical mucous & impairs sperm transport Alters endometrial lining Prevents implantation
Dosage and formulations
EE always ≤ 50 µg 20 μg pill in randomized trial had reduced breast tenderness and bloating 20 mcg pills have higher failure rate with missed pills (Medical Letter Treatment Guidelines 2007) 10 mcg pill approved (Lo-Lo-Estrin ® ) Progestin ≤ 1 mg Primarily responsible for contraceptive efficacy
OCP - Yasmin
®
, Yaz
® First with progestin – drospirenone 3 mg Analog spironolactone Avoid in renal insufficiency, hepatic dysfunction or adrenal insufficiency Manufacturer recommends measuring K + during 1 st cycle in women regularly taking drugs that may increase K + (ACE, ARB or NSAID) Studies examining hyperkalemia & associated arrhythmias have not found higher rates including women taking K + sparing drugs
OCP - Yasmin
®
, Yaz
® Equivalent benefit with acne Improves hirsutism & lowers BP Initial weight loss followed by gradual weight return Thromboembolism has been reported
Audience Question
18 year old female with mild acne wants to start OCP for contraception. Normal physical, no prior OCP use. Periods variable from 26 – 45 days. For this patient I would prescribe a: a) b) c) d) Monophasic pill Biphasic pill Triphasic pill Nonhormonal contraception method
Monophasic pills
Estrogen Progesterone Day 1 Day 21
Biphasic pill
(Necon ® ) Estrogen Progesterone Day 11
Triphasic pills
Estrogen Progesterone Day 8 Examples – Caziant ® ; Cylessa ® ; Necon 7/7/7 ® ; Ortho Novum 7/7/7 ® ; Ortho Tri-Cyclen TriNessa ® ; Velivet ® ® ; Tri-Sprintec ® ; Day15
Triphasic pills
Estrogen Progesterone Ex. Tri-Norinyl ® ; Aranell ® ; Leena ® Day 8 Day 17 Day 6 Ex. TriNessa ® ; TriVora ® ; Enpresse® Day 13 Ex. Estrostep Fe ® ; TriLegest Fe ® ; Tilia Fe ® Day 7 Day 12
Four-phase pill
(Natazia®) estradiol valerate/dienogest 3 mg/0 mg x2, then 2 mg/2 mg x5, then 2 mg/3 mg x17, then 1 mg/0 mg x2 Estrogen Progesterone Day 3 Day 8 Day 25 Day 27
Monophasic, Biphasic or Triphasic?
Biphasic & triphasic pills were developed to reduce side effects of monophasic pills Biphasic with norethindrone associated with inferior cycle control compared to triphasic with levonorgestrel [Cochrane Review 2005] Progestin may be more important than phasic type Monophasic pills give better cycle control Triphasic pills offer no physiologic advantage No data to support triphasic over monophasic pills
OCP general benefits
Decreased dysmenorrhea Reduced menstrual flow Reduced risk of anemia Improves acne Eliminate mittelschmerz Decreased risk of ectopic pregnancy Decreased risk of PID Decreased sxs of PMS Improvement in endometriosis Suppression of ovarian & breast cyst formation
OCP – Benefit
Endometrial cancer reduced 50% reduction if used in prior 12 months Maximum protection if use continues for 3 years Protection lasts for 15 + years High or low dose pills provide protection
OCP – Benefit
Ovarian cancer reduced 40% reduction in risk over nonusers High dose or low dose pills - same benefit Begins after 3-6 months of use 80% reduction after 10 years of use Reduced risk with family history ovarian CA & 4-8 yrs. use
OCP Cardiovascular Risks
Increased risk of CVD in smokers over age 35 Small increased risk MI with 2 nd generation progesterones Only with current users – no lingering effect Slight increased risk of ischemic stroke 2-6 fold increase of ischemic stroke with history of classic migraine
OCP - Risks
Headaches May increase or decrease Headaches attributed to initiation of OCP tend to improve over time If HA persists with normal BP & no focal deficit Lower dosage of estrogen, progestin or both (no evidence effective) If HA persists with increased BP or focal deficit Discontinue OCP
OCP - Risks
OCP use associated with increased risk of developing systemic lupus erythematosus (SLE) Especially if started recently [Bernier 2009] However, very low risk overall
VTE Risk
VTE Risk 3-6 fold increased risk VTE, highest first 6-12 months of use (SOR B) Older women have greater risk > age 39 100/100,000 person-years Adolescents - 25/100,000 person-years Obesity doubles the risk
VTE Risks
VTE Risk Risk decreases with longer duration of use For same estrogen dose - desogestrel & drospirenone have significantly higher risk [Lidegaard 2009] Grapefruit juice can augment bioavailability of EE [Grande LA 2009]
OCP Risks - EBM
Risks (SOR B) Increase in cervical cancer after 8 or more years of use after adjusting for HPV infection Risk of CIN 2 - 3 with oncogenic HPV Decreased with depot-medroxyprogesterone (DMPA - Depo-Provera ® ) No association with combination OCPs [Harris 2009]
OCP Risks/Benefits - EBM
No increased risk of weight gain (SOR A) Weight gain does occur with DMPA – 5.1 kg No increased risk breast cancer (SOR B) No consistent change in breast milk production (SOR A) Or in infant growth or weight (SOR B) Women who use OCP are not at an increased risk of death later in life In fact a net benefit was found
OCPs can be used with these conditions
Diabetes mellitus < 35 years old Nonsmoker > age 35 Smokers < 35 years old Obese women Caution > age 39 Controlled hypertensive Ulcerative colitis Pituitary adenomas After gestational diabetes
OCPs and Stable SLE - EBM
OCPs are safe & do not increase the risk of flares in women with stable SLE InfoRetriever Randomized controlled trial (double-blinded) Level of Evidence (LOE) 1 b http://www.infopeoms.com/irsearch/search_details.cfm?ID=802 05&ResultKey=E&title=OCPs%20safe%20in%20women%20wi th%20SLE
OCP Contraindications
History of DVT, PE or arterial clotting Family history clotting or thrombotic events Family history (FH) if positive is risk factor VTE Ask if parent or sibling ever had VTE Positive FH if 1 relative was < 50 yo when VTE occurred Positive FH if 2 or more relatives at any age had VTE [Bezemer 2009]
OCP Contraindications
Smoking and ≥ 35 years old Uncontrolled hypertension Migraine with aura Undiagnosed genital bleeding
OCP Contraindications
Pregnancy – not harmful, just too late Sickle cell (SS) or sickle C (SC) disease not absolutely contraindicated DMPA may be preferable for SS disease
Duration of Use
Non-smokers – OCPs can be used into menopause To determine if menopausal d/c OCP & obtain FSH one month later If FSH > 40 ng/mL = menopausal Not proven reliable indicator, alternative just stop in early to mid 50s Smokers – stop at age 35 If treating vasomotor symptoms consider continuous active pills
Drug Interactions
Vitamin C Increases estrogen level Can induce nausea Discontinuation of vitamin C may precipitate bleeding Decreased estrogen level Antibiotics Unclear impact on efficacy
Drug Interactions
Anticonvulsants Advise patients to use a different form of contraception Because some anticonvulsants may reduce efficacy of OCPs If you & patient decide to use OCP, use pill with 50 µg EE If breakthrough bleeding occurs with that pill Patient should use alternative contraceptive method
Frequency of menstruation
Before initiating OCPs ask how often the patient wants to menstruate Monthly? (Every 4 weeks) Quarterly? (Every 91 days) Never?
Rarely Menstruate
Seasonale ® (2004) 84 days active pills with levonorgestrel (0.15 mg) & EE (30 mcg) 7 days placebo Increased risk unsuspected bleeding first 6 months of use
Never Menstruate
Lybrel ® approved in 2007 for continuous use 365 days active pills EE 20 mcg & levonorgestrel 0.09 mg every day
Continuous OCPs
Women who use a continuous combination OCP will have less bleeding without an increase in adverse effects Reduced frequency of hormone withdrawal side effects Reduced headache, pelvic pain, bloating, breast tenderness
Susie
15 year old female who came in to discuss contraception Questions that were asked Family history negative for VTE or cancer Wants to menstruate monthly Given prescription for generic monophasic pill and she was told to start the pills today Had a negative pregnancy test in the office
OCP formulations
OCP
Standard Mircette ® Seasonique ® Loestrin ® 24 Fe Yaz ® (20 mcg EE) Femcon ® pill) Natazia™ Fe (chewable
Active
21 21 84
24 24
21
26 Placebo Low dose active
7 0 2 0
5
7
4 4
0 0 7 0 2 0
yo patient. No previous OCP use. Normal family history & physical exam. When will you advise
9%
a) b) c) d) The Sunday after her next period starts The first Sunday after next period ends T he Su a The first day of her next period fi rs t Su fi rs t d ay ..
.
d ay I se e The day I see her in the office T ...
Starting OCPs – 3 Options
1.
“Sunday start” – take the 1 st 1 st pack the 1 st pill of the Sunday after onset of menses Reduces menses on weekend May not suppress ovulation with first cycle Advise additional contraception 1 st month
Starting OCPs – 3 Options
2.
“First-day start” - take the 1 st 1 st pack the 1 st pill of the day of next menses Easier to remember & explain Immediately protective as birth control Less breakthrough bleeding
Starting OCPs – 3 Options
3.
“Visit day start” - take the 1 st pack the day of the visit pill of the 1 st “Quick start” - watch patient take 1 st pill Negative pregnancy test & no intercourse prior 2 weeks, no immediate follow-up If intercourse within prior 2 weeks, repeat pregnancy test in 2 weeks Additional contraception the first 7 days
Quick-Start contraception
Main benefit is reduced time explaining how to start pills [Westhoff 2007] No evidence reduced risk of pregnancy or discontinuation rates for OCPs [Cochrane 2008] Fewer women on quick-start Depo-Provera became pregnant than women who started another method [Lopez 2008]
The Prescription
Dr. Understanding Sarasota, Fl Jane Smith Sig:
3 OCP Packs Refill: x 3
Dr. Understanding Sarasota, Fl Jane Smith Sig:
1 OCP Packs Refill: x 12
Better Option?
Dr. Understanding Sarasota, Fl Jane Smith Sig:
13 OCP Packs Refill: x 0
Dispensing 13 cycles at a single visit lead to better continuation rates & decreased cost [Foster 2006] Women who received 13 cycles were more likely to have PAP testing & chlamydia screening
Audience Question How often are pills forgotten?
During a three month period, how many pills does the average woman miss each cycle?
a) b) c) d) e) 1.2
2.6
3.5
4.1
4.9
Missing pill instructions
First ask which pill(s) were missed: If placebo pill just skip it If active pill and < 24 hrs late Take immediately If active pill and ≥ 24 but < 48 hrs late Take both pills at the same time Additional contraception not required
Missing pill instructions
If 2 active pills missed Double up for 2 days Use additional contraceptive method for 7 days Consider emergency contraception if unprotected intercourse If ≥ 3 active pills missed Stop pills and begin new pack Use additional contraceptive method for 7 days Consider emergency contraception if unprotected intercourse Discuss alternative contraceptive options that do not require daily compliance
Most Dangerous pill to Miss?
Most dangerous pill to miss is the 1 st pill of the new pack Pill free > 7 days increases risk ovulation Use additional form of birth control until taken 7 consecutive active pills Stress compliance with starting each new pack
Audience Question
26 y.o. patient at her 6 weeks postpartum visit requests contraception. Exclusively breastfeeding. Used combination OCP is the past. Which contraceptive option would you recommend?
a) b) c) d) Progesterone IUD Low-dose combination OCP Progesterone only OCP Continue exclusively breastfeeding and return for contraception at 6 months or when supplementing with formula
Progestin only pills
Thicken cervical mucous & prevent sperm ascending through os Erratic suppression ovulation Irregular bleeding more common Daily compliance crucial Same time every day (2-3 hr difference can cause bleeding, allow ovulation) Are not contraindicated in smokers over age 35
OCP - Postpartum
Can begin combination OCP ≥ 3 weeks postpartum after delivery ≥ 20 weeks gestation Starting < 3 weeks postpartum associated with increased risk of VTE Balance this against risk of unwanted pregnancy which has greater risk of VTE For delivery of < 20 weeks gestation can begin combination OCP immediately
OCP – Breast feeding
Can start combination OCP at 6 weeks post-partum if lactation is well established and other forms of contraception are not acceptable [ACOG Position Statement 2004]
Audience Question
26 y.o. patient at her 6 weeks postpartum visit requests contraception. Exclusively breastfeeding. Used combination OCP is the past. Which contraceptive option would you recommend?
a) b) c) d) Progesterone IUD Low-dose combination OCP Progesterone only OCP Continue exclusively breastfeeding and return for contraception at 6 months or when supplementing with formula
Progestin only pills
Thicken cervical mucous & prevent sperm ascending through os Erratic suppression ovulation Irregular bleeding more common Daily compliance crucial Same time every day (2-3 hr difference can cause bleeding, allow ovulation) Are not contraindicated in smokers over age 35
OCP - Postpartum
Can begin combination OCP ≥ 3 weeks postpartum after delivery ≥ 20 weeks gestation Starting < 3 weeks postpartum associated with increased risk of VTE Balance this against risk of unwanted pregnancy which has greater risk of VTE For delivery of < 20 weeks gestation can begin combination OCP immediately
OCP – Breast feeding
Can start combination OCP at 6 weeks post-partum if lactation is well established and other forms of contraception are not acceptable [ACOG Position Statement 2004]
Hormonal Contraception Other than Oral
Contraceptive Patch
Ortho Evra ® (EE 20 mcg; norelgestromin 150 mcg/day) Apply abdomen, buttocks upper torso (exclude breast) or upper outer arm One patch a week for 3 weeks, 4 th patch free week
Contraceptive Patch
Equally efficacious to OCP Side effects Breast discomfort, headache, nausea & cramps – perhaps more than with OCP Less effective - women > 90 kg FDA warning of higher hormone levels than previously reported – may increase risk of VTE
Hormonal vaginal ring
NuvaRing ® mcg/day - EE15 mcg & etonogestrel 12 One ring for three weeks No ring for one week If ring is out > 3 hours use additional contraception until ring in place for 7 days Does not have to be in specific position Hormones absorbed anywhere in vagina
Hormonal vaginal ring
NuvaRing ® Contraceptive hormone levels for 35 days Alternative regimen One ring a month Same day of the month (e.g. 12 th of every month) Reduces number of menses & hormonal withdrawal side effects [Sulak 2008]
Patch & Ring – EBM
Cochrane review found: Patch caused more side effects than OCP Ring caused fewer side effects than OCP Except vaginal discharge & vaginitis
Obese women - EBM
What hormonal contraception is most effective?
Depo-Provera & NuvaRing
®
body weight (SOR B) are not affected by Obese women using oral contraceptives have increased risk of pregnancy (SOR B) [Clinical Inquiries 2007] However, new evidence found ovarian suppression was the same for obese women who were consistent users of OCP
Contraceptive Failure Rate
No method Method Diaphragm with spermicide Condom – male OCPs Transdermal Transvaginal Injectable IUD – copper IUD – progesterone Implant Typical Use
85% 16% 15% 8% 8% 8% 3% 0.8% 0.2% 0.05%
Perfect Use
85% 6% 2% 0.3% 0.3% 0.3% 0.3% 0.6% 0.2% 0.05%
Emergency Contraception (EC)
Woman at risk for unwanted pregnancy Condom broke or slipped Forced intercourse Intercourse and no method of BC Diaphragm or cervical cap dislodged Two or more OCPs missed or forgotten > 12 weeks from last depo progesterone injection Missed first pill of OCP
Emergency Contraception
Woman at risk for unwanted pregnancy Contraceptive patch (Ortho Evra
®
) Off > 24 hours during active week Left on > 9 days > 2 days late putting on active week patch NuvaRing
®
Taken out > 3 hours during active weeks Left in > 5 weeks in a row > 2 days late inserting new ring
Emergency Contraception
Mechanism of action Inhibits or delays ovulation if prior to ovulation Interferes with egg/sperm transport Alters endometrium and prevents implantation Does not terminate established pregnancy ACOG - only contraindication is pregnancy Because it doesn’t work History of ectopic pregnancy not contraindication Careful follow-up since higher risk of repeat ectopic Smoking & over age 35 not contraindication
Emergency Contraception
Progestin only (Plan B ® ) 0.75 mg levonorgestrel – two doses 12 hours apart Single 1.5 mg pill available (Plan B One Step ® )
Emergency Contraception
Fewer side effects & better efficacy 95% within 24 hrs, 85% within 25-48 hr Can be used up to 5 days after intercourse No clinical exam or pregnancy test is necessary before EC EC may be used again even if used before within the same menstrual cycle Available OTC for women ≥ 17 yo
Emergency Contraception
Ulipristal (Ella ® ) approved for EC Selective progesterone receptor modulator (SPRM) – 30 mg single dose Remains equally effective up to five day after unprotected intercourse Possibility it is less effective in women with BMI > 30 Requires a prescription No significant side effects but long-term data is not yet available
Emergency Contraception
Follow-up care Document patient has normal menses within 21 days Obtain B-hCG level if no menses in 21 days Discuss starting ongoing contraception at the start of induced menses
Key Points Hormonal Contraception
No one OCP has any unique advantage Become comfortable with 4 formulations that allow adjustment in estrogen & progesterone dosage Weigh risks vs. benefits before initiating hormonal contraception Compliance may be enhanced with alternative delivery system (patch, ring) Discuss availability of emergency contraception