Contraceptive Technology Faculty Update Leigh Beasley, MD, FAAFP Emory University Regional Training Center Satellite Conference and Live Webcast Atlanta, Georgia Wednesday, October 25, 2006 2:00 - 4:00 p.m. (Central Time) Produced by the Alabama Department of Public Health Video Communications and Distance Learning Division Program Objectives Program Objectives • Describe current thinking on • Describe the new World Health Organization's (WHO) medical contraceptive efficacy and the status eligibility criteria; Intrauterine Device of experimental contraceptives. (IUD) and teens, IUD and Plevic Inflammatory Disease (PID); • Describe the interrelationships of spermicides; and known medical contraception methods with thrombogenic mutations and oral specific drugs, reproductive contraceptives. disorders and other health problems. • Discuss management of common contraceptive problems. Contraceptive Use in the Half of All Pregnancies in the US: 2002 Report United States Each Year Are • Percentage of men and women who Unintended used contraception ranged from 67% Unintended Pregnancy- (Guam) to 88% (Idaho). Miscarriage 6% Unintended • Women reported OC’s as the Pregnancy- Intended Birth Pregnancy- predominant method in 49 areas 19% Birth 43% followed by tubals, condoms and vasectomy. • Men reported tubal, vasectomy, OC’s, Unintended and condoms. Pregnancy- Abortion Intended 23% Pregnancy- • Note lack of “new methods” in the top Miscarriage Pregnancies four. 9% (6.3 Million) 1 The Oral Contraceptive Cycle OC Developments • Progestin prevents luteinizing • New Progestin: Drospirenone; hormone (LH) surge. • Estrogen suppresses follicle- Yasmin. stimulating hormone (FSH) and follicular development. • Berlex has obtained FDA approval • Together, the hormones in for Yaz (20 mcg EE/3 mg combination OCs inhibit proliferative changes in drospirenone) for BC and PMDD uterus, leading to endometrial (unique dosing 24 days active pills atrophy. and 4 placebo pills). • When placebo pills are taken, a “pill period” results. OC Developments Depo-Provera • New Estrogen doses: 25mcg; • November 17, 2004: the FDA issued a Cyclessa, Ortho-Tricyclen Lo. “black box” warning recommending • Extended Cycle Use: Seasonale, that Depo-Provera be used long-term Seasonique. (i.e. more than two years) only if all • Widening EC use. other pharmacologic contraceptives • “Natural” estrogen pills and are not appropriate or tolerated due nonsteroidal progesterone agonist (tanaproget). to bone loss data in adult women. Depo-Provera and Effect of Contraception on BMD in Teens Bone Mineral Density • NIH-funded study (J. Adoles Health 2004) • Studied women ages 18-33 seeking – 370 girls (mean age, 15). contraception. – 53 chose Depo, 165 chose OC’s (20 ug of estrogen) and 152 chose no • Injectable Depo hormonal contraception. medroxypgogesterone acetate – BMD values after 12 months. 150mg vs. 0.030 mg EE plus 0.15 mg • At lumber spine: -1.4%, +2.3% and desogestrel vs. 0.035 mg EE plus 1.0 +3.8%. mg norethindrone vs. controls (no • At the hip: -2.2%, +0.3% and +2.3%. hormonal contraception). – Clinical relevance ? • Followed for 2 years. 2 Effects of Contraception on DMPA and Bone Health Bone Mineral Density • Three studies that indicate BMD is • Depo users-average loss from baseline comparable in former and never of 5.7 % (in spinal BMD). users following discontinuation of • Desogestrel OC-average loss form DMPA. baseline of 2.0 % (not statistically – Petitti DB et al (Obstet Gynecol significant). 2000;95:736-744). • Norethindrone- no significant change – Scholes D et al (Epidemiology in BMD. 2002; 13:581-587). • Controls-average gain of 2.6 % in BMD. – Scholes D et al (Arch Pediatr • Clinical relevance? Adolesc Med 2005; 159: 139-144). Effect of Pregnancy DMPA and Bone Health and Lactation on Bone • Data presented at the May 2005 Mineral Density ACOG meeting (co-author Andrew • Bone turnover is reduced in early Kaunitz, MD). pregnancy, returned to normal during the third trimester and increased in • Loss of BMD of approximately 1%- postpartum lactating women 2% annually, with slower loss after (Cole et al. 1987) that and substantial recovery • No evidence that high parity is following discontinuation (followed associated with an increased incidence patients for 2 years after DMPA was of osteoporotic fractures in later life discontinued). (Alffram, 1964; Walker et al. 1972). DMPA and Bone Health World Health Organization DMPA Statement • Complete recovery of BMD was not • July 2005: There should be no found at all skeletal sites assessed restriction on the use of DMPA, including no restriction on duration (but would it have if followed for > 2 of use, among women ages 18-45 years post DMPA?). who are otherwise eligible to use the method. 3 World Health Organization World Health Organization DMPA Statement DMPA Statement • Among adolescents (menarche to • Since the data are insufficient to less than 18) and women over 45, the determine if this is the case with long advantages of using DMPA generally term use among this age group, the outweigh the theoretical safety overall risks and benefits for continuing use of the method should concerns regarding fracture risk. be reconsidered over time with the individual user. Lower Dose, Subcutaneous Lower Dose, Subcutaneous Depo-Provera Depo-Provera • Study compared LDSQ Depo • Ovulation was suppressed in all (104mg/0.65ml) with IM Depo participants for at least 3 months. (150 mg/ml). • Median time to return to ovulation • Confirmed study participants were was similar in the two groups (183 ovulatory. days in the IM group and 212 days in • Received single injection and the SQ group). followed up until they ovulated • Dose and maximum serum (up to 12 months). concentration are substantially lower • 19 women who received IM and 39 with the SQ formulation…so ? Less received SQ were evaluated. side effects? NuvaRing NuvaRing®: Metabolic and • Non-biodegradable, flexible, Safety Conclusions transparent vaginal ring. • Minimal effect on lipid parameters. • Contains two active components: • No clinically relevant effect on ethinyl estradiol and etonogestrel (an estrogen and a progestin). carbohydrate metabolism. • Releases 0.015 mg/day of • Minimal effect on hemostatic ethinylestradiol and 0.120 mg/ day of variables, comparable with 30 EE/150 etonogestrel over a three week period. LNG COC. 4 NuvaRing®: Metabolic and Nuva Ring Update Safety Conclusions • Effectiveness not lower in very heavy • Low androgenic effects. women (Westhoff-ACOG 2005). • No adverse effect on blood pressure. • Continuous use can be based on a “calendar approach” since the Nuva • No unfavorable effects on the cervix Ring is active for 35 days, not 21 and vagina. (Timmer et al Clin Pharmokin 2000;39:233). • Clinicians can obtain free fitting rings by going to www.nuvaring.com California Women’s Health Emergency Contraception: Survey • 6198 women (age 18-44) were asked The Nations Best-Kept “If a woman has unprotected sex, is there anything she can do in the 3 Secret days after intercourse that will prevent pregnancy?” – Slightly more than _ said yes, 1/3rd said no and around 10% said they didn’t know. California Women’s Health Why Everyone Should Know Survey About EC 43% of the decrease in abortions in – 19% of those who answered yes • the US in the last 5 years has been listed incorrect responses to “what attributed to the use of EC. can she do?” (included RU 486 and • Up to 51,000 pregnancies are prevented annually by the use of EC. douche) and 7% gave ambiguous • (Finer et al. Perspec on Sexual answers (“seek medical help”). and Reprod health 2003) • Works like LAM. 5 Emergency Contraception EC’s Effects on Ovulation • Studied 58 women with regular Mechanism of Action menstrual cycles (either had tubals • Inhibition of ovulation. or IUD). • Decreases the probability of • Treatment regimens: two 0.75 mg fertilization after ovulation. doses of levonorgestrel (12 hours • Changes in the endometrium apart), single 0.75 mg dose of (decreasing the likelihood of levonorgestrel plus placebo or double dose of placebo. implantation). • Randomized to take meds when • Does NOT interfere with an leading follicle reached a diameter of established, post implantation 12-14 mm (Group I), 15-17 mm pregnancy. (Group II) and > 18 mm (Group III). EC’s Effects on Ovulation EC’s Effects on Ovulation • Within 5 days of treatment, there was • Percentage of cycle either ovualtory no ultrasound evidence of follicular dysfunction or no follicular rupture rupture (i.e., no ovulation) in 44%, was similar in with 3 regimens in 50% and 36% of cycles with 2 levo. Group 1, significantly higher with doses, 1 dose and placebo. levo than placebo in Group II and • Ovulatory dysfunction (disordered significantly higher with one dose surges in LH and FSH) in 35%, 36% levo than placebo in Group III. and 5%. EC’s Effects on Ovulation Emergency Contraception • Caution in interpreting results: used • Most effective if taken within 72 hormonal parameters and ultrasound hours of unprotected intercourse and did not test EC’s efficacy. (the sooner the better). • 13% of women with dominant follicle • New data suggests equal (i.e. > 18 mm) did not ovulate when effectiveness if both doses are taken treated with placebo. together and may be used up to 120 • Single dose used in this study was hours after unprotected intercourse. not the “single dose” used in • EC treatment is indicated regardless treatment studies. of the cycle day on which – (Contraception 2004 Dec.) unprotected intercourse occurred. 6 Emergency