Hormonal Contraception – communication in special risk populations ALFRED O. MUECK MD. PharmD. PhD. University Women's Hospital of Tuebingen, Germany Dept. of Endocrinology and Menopause, Head Centre of Women's Health of Baden-Württemberg, Head Germany

ESC Congress; The Hague, The Netherlands; May 19-22, 2010

Hormonal Contraception (HC) - Counseling 1. Counseling about contraceptive options: Hormonal methods, and women's preference 2. Counseling about benefits beyond contraception 3. Counseling in special populations: Adolescense, post partum, perimenopause 4. Counseling about possible side effects and risks 5. Counseling in women with preexisting disease ALFRED O. MUECK: ESC Congress; Den Hague, Netherlands; May 2010

Hormonal Contraception (HC) - Counseling 1. Counseling about contraceptive options: Hormonal methods, and women's preference 2. Counseling about benefits beyond contraception 3. Counseling in special populations: Adolescense, post partum, perimenopause 4. Counseling about possible side effects and risks 5. Counseling in women with preexisting disease ALFRED O. MUECK: ESC Congress; Den Hague, Netherlands; May 2010

Contraceptive options for women • Estrogen/progestin – – – –

oral transdermal vaginal injectable

• Progestin only – – – –

oral injectable implant IUS

• Emergency contraception

• Non-hormonal – copper IUD – barrier methods (condom, cap, sponge, diaphragm) – abstinence – fertility awareness – sterilization

Oral Contraceptives (OC): Available Regimens Monophasic Combinations

Biphasic Combinations

Triphasic Combinations

Sequential Combinations Progestogen Only Pills ( Desogestrel, NETA Levonorgestrel )

Ethinyl Estradiol (EE) : red; progestogen: yellow

Reliability of most used reversible hormonal contraceptive methods (HC) Pearl Index Combined Oral Contraceptives

0.03 – 0.5

Progestin Only Pills

0.4 – 4.3

Injectable Progestin Only preparations

0.03 – 0.9

Progestin Only Implants

0.1 – 0.3

Levonorgestrel – IUD

0.05 – 0.2

Copper – IUDs

0.1

Condoms No Contraception

– 3 7 – 14 > 80

modified after Leidenberger FA. Clinical Endocrinology, Springer New York 2004

Top 10 criteria for choosing a Contraceptive Method (HC) • Contraceptive reliability • Good tolerability • No effect on weight • Positive effect on well-being • Good cycle control • Low dose of hormones • Positive effect on physical PMS • Long term effect • Positive effect on bleeding problems • Positive effect on emotional PMS Q: Which of the following characteristics of hormonal contraceptives is extremely important for you when selecting a hormonal contraceptive method?

Pan-European FC study 2006, Bayer Schering Pharma AG data on file

Hormonal Contraception (HC) - Counseling 1. Counseling about contraceptive options: Hormonal methods, and women's preference 2. Counseling about benefits beyond contraception 3. Counseling in special populations: Adolescense, post partum, perimenopause 4. Counseling about possible side effects and risks 5. Counseling in women with preexisting disease ALFRED O. MUECK: ESC Congress; Den Hague, Netherlands; May 2010

HC: Benefits Beyond Contraception • Many hormonal contraceptive methods (HC) have non-contraceptive benefits • Contraceptive methods are often used for indications other than birth control • Utilizing the non-contraceptive benefits may help to improve adherence with a contraceptive method

The ESHRE Capri Workshop Group. Hum Reprod 2005;11:513-25. SOGC Clinical Practice Guidelines. JOGC 2004;143:219-54.

Benefits of HC use estimated from literature Contraceptive Benefits

Reduction %

Pregnancy Deaths at birth Abortions (spontaneous/induced) Extrauterinal Pregnancy

> 90 > 90 > 90 > 90

modified after Rabe T, Runnerbaum B. Fertility Control Update 2000 Springer New York, pp. 99-120

Noncontraceptive Benefits

Reduction %

Cycle disturbances Dysmenorrhea Anemia Acne, Hirsutismus Pelvic inflammation Rheumatoid arthritis

25-50 25-50 25 10-50 50 50

Benign Breast Disease Benign ovarial tumours Ovarial follicle cysts

25-50 25 25

Ovarial carcinoma Endometrium carcinoma Colon/Rectal carcinoma

50 50 50

Hormonal Contraception (HC) - Counseling 1. Counseling about contraceptive options: Hormonal methods, and women's preference 2. Counseling about benefits beyond contraception 3. Counseling in special populations: Adolescense, post partum, perimenopause 4. Counseling about possible side effects and risks 5. Counseling in women with preexisting disease

ALFRED O. MUECK: ESC Congress; Den Hague, Netherlands; May 2010

Counseling in special populations: Teenager / Adolescents

Counseling about frequency of STI and HPV: - Of all STIs / year, 50% are in young people ages 15-24 y. - Of all newly diagnosed HIV cases, 25% are under age 22 y.

Counseling about risk and prevention of cervical cancer: - Highest risk during adolescence, if multiple sexual partners

Counseling for special populations: Teenager / Adolescents - in this age-group HC methods are first-line options for contraceptive protection - adding a condom for STI protection may be appropriate and highly beneficial Teens like especially: Bleeding control, decline in menstrual cramps and acne 

Choice of HC according to those special benefits !

Counseling for special populations: Following pregnancy and during lactation

Recommendations for women who want effective contraception



Consider official recommendations by labeling and for example published by WHO (2004, 2009) in breast-feeding and non-breast-fedding women

Counseling for sexually active postpartum women

Counseling for perimenopausal women ( > 35 y. ) Consider special benefits of Hormonal Contraception (HC) 1. most efficacious reversible method to avoid pregnancy  HC most important for this age-group!

2. efficacious bleeding control, lowered risk for anemia  irregular bleedings key symptom of perimenopause!

3. decrease of climacteric symptoms  HC effective, but consider HRT if no contraception is needed!

4. prevention of bone loss  HC effective, but consider HRT if no contraception is needed!

5. decreased risk of ovarian, endometrial, colorectal cancer  high cancer fear in this age-group!

Counseling for special populations: Perimenopausal women Counseling in this age-group should especially include to investigate:

1. General health conditions, especially CVD - significant risk factors for coronary artery disease and stroke? - preexisting diseases like diabetes mellitus? - clotting problems, previous thromboembolic events? - family history of CVD (MI, stroke, venous thromboembolism)? - during previous pregnancy: hypertension, thrombosis, diabetes?

2. Gynecological issues - sexual activity: need for contraception? - bleeding problems: need for bleeding control? - other gyn. problems like fibroids and endometriosis? - degree of perimenopausal symptoms: Counseling about the benefits and risk of HRT

Efficacy in perimenopausal symptoms comparing COC with HRT in Cross-over switching during menopause - perimenopausal women, n = 601 ( mean age 49; SD 3.1 ) - all on combined contraceptive pills (COC) - switched from COC to HRT within 0 - 8 weeks - endpoints: 1) comparing bleeding patterns before and after switch 2) comparing efficacy in climacteric symptoms

 bleeding pattern not influenced by duration of switching, phase type of COC, or dosage of EE 

during COC 56% had hot flushes, which were eliminated in 90% within 6 months's of HRT !

Mueck AO et al. Geburtsh Frauenheilk 2005; 65: 389-395

New COCs with Estradiol instead Ethinyl-Estradiol – Expected clinical advantages - much lower hepatic effects (clotting factors, drug-interactions) - stronger bone-protective effects - stronger effects for perimenopausal women with hot flushes - stronger positive central nervous effects (mood, sexual dysfunction etc.)

- stronger positive effects in vagina - less negative metabolic effects (lipids, carbohydrates) - stronger vasodilative effects (cardiovascular protection?)

Hormonal Contraception (HC) - Counseling 1. Counseling about contraceptive options: Hormonal methods, and women's preference 2. Counseling about benefits beyond contraception 3. Counseling in special populations: Adolescense, post partum, perimenopause 4. Counseling about possible side effects and risks 5. Counseling in women with preexisting disease ALFRED O. MUECK: ESC Congress; Den Hague, Netherlands; May 2010

Side effects of HC dependent on E- or/and P-component

Counseling about possible side effects and risks: Consider especially contraindications 1. preexisting (known) cardiovascular diseases (CVD), including disease that affects vascular system (e.g. PAD, sLE)

2. significant risk factors for CVS - instable hypertension; cigarette smoking - diabetes with micro- or macroangiopathy, insulin resistance - long-standing lipid-abnormalities (need for statin therapy) - long-standing obesity - (non menstrual) migraine headaches (with and without aura = forwarning for an attack)

3. history or increased risk of significant clotting problems - deep vein thrombosis, pulmonary embolism - known thrombogenic mutations - acute or chronic severe thrombophlebitis - prolonged immobilization, impending major surgery

4. cancer of breast, uterus, cervix 5. acute liver disease, current gallbladder disease

Hormonal Contraception (HC) - Counseling 1. Counseling about contraceptive options: Hormonal methods, and women's preference 2. Counseling about benefits beyond contraception 3. Counseling in special populations: Adolescense, post partum, perimenopause 4. Counseling about possible side effects and risks 5. Counseling in women with preexisting disease ALFRED O. MUECK: ESC Congress; Den Hague, Netherlands; May 2010

Counseling for special populations: Women with preexisting medical disease

- General counseling ( e.g. life-style, diet, medication ) - special step-wise questions to choose the optimal contraceptive method

Counseling for women with preexisting medical disease General health counseling to modify lifestyle factors Lifestyle factors with special impact on medical disease and contraceptive option: - Cigarette smoking - obesity; excess caloric intake - poor nutrition ( high in saturated fats, salt, simple carbohydrates )

- inactivity; lack of exercise - drug abuse: illicit, alcohol, and prescription - high-risk sexual behaviour ( multiple partners, unprotected intercourse ) - recurrent

Sexually Transmitted Infection (STI) - low level of maturity and reliability

Counseling for women with preexisting medical disease Step-wise 5 key questions to choose optimal contraceptive method

1. Is she a candidate for a HORMONAL contraception ? 2. If she COULD use hormonal contraception in general: Is she a candidate for EE-containing contraceptive ? 3. If she COULD use Combined Oral Contraceptives (COC): Best dose, best application form? Special benefit/risk regarding the progestin component ? 4. If she should NOT use estrogen: What is the best progestin-only contraception ( progestin, route, dosage ) ? 5. Is she a candidate for IUD ( copper-IUD, LNG-IUD ) (Question independent or dependent on answers to questions above!)

THANK YOU FOR YOUR ATTENTION !

Reasonable application of OC in the treatment of PCOS 1. All OC have benefits in all 3 key symptoms of PCOS: hyperandrogenism, cycle disturbances and ovarian changes. 2. Main mechanisms of OC are decrease of LH, increase of SHBG, with additional benefit using anti-androgenic progestogens. 3. However, all OC man increase cardiovascular risks, but different dependent on dosage and progestogen component. 4. Thus, the indication for use of OC as well as choice of OC must be decided on a very individualized basis. 5. Considering dosis and different receptor affinity, contraceptive and non-contraceptive benefits of OC should outweigh possible risks.

Pearl Index to quantify Reliability of Contraceptive Method ( without considering user failures ) - Definition: Number of unwanted pregnancies per 100 years of use ( = 100 'women-years' ) 

number of pregnancies, if 100 women use the method 1 Year

- Pearl Index 1(-2)

reliable contraception not reliable contraception

The reliability of hormonal contraceptives is not achievable by any other current available reversible method of contraception.

OCs: There is more than Contraception...

Contraceptive Benefits  Unwanted pregnancies  Abortions (induced & spontaneous)  Ectopic pregnancies  Morbidity/Mortality in pregnancy

+

Additional Benefits            

"Cycle“ control Dysmenorrhea Anemia Acne, Seborrhea PCO Premenstrual Syndrome Pelvic inflammatory disease Benign ovarian tumors Benign breast tumors Endometriosis Ovarian-Ca. Endometrium-Ca.

~50% ~60% ~25% ~80% ~50% ~25% ~50% ~80% ~50% ~50% ~50% ~50%

+

Emerging Benefits    

Bone mass Colorectal cancer Rheumatoid arthritis Hyperandrogenic anovulation

Women’s Concerns about oral contraception have changed over time

Reliability

1965

2000

Reported reduction on cancer risks with specific contraceptives compared with non-users

Various good studies: No increase of breast cancer e.g. CASH-Study (2002); UK Royal College Study (2007)

Metabolic side effects of contraceptive methods dependent on E- or/and P-components

Counseling for special populations: Teenager / Adolescents Realistic expectations on condoms and non-hormonal contraceptives: - Limits on contraceptive effectiveness - Limits on STI protection

Accurate contraceptive information: - Options and proper use of OC - Emphasis that OC and STI protection must relialable when method used consistently and correctly

Counseling in special populations: Adolescents: Often first diagnosis of PCOS PolyCystic Ovary Syndrome (PCOS) – Definition Rotterdam PCOS Consensus Workshop 2003 European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine

1) Hyperandrogenism (clinical or biochemical signs) 2) Chronic Oligo- or anovulation (severe oligomenorrhea)  frequently first sign of PCOS in adolescents ( especially without obesity ! ) 3) Polycystic looking ovaries (on ultrasonography) and exclusion of other etiologies  Diagnosis PCOS requires two of these 3 criteria  Controversial 3); in USA most clinicians believe, only 1)+2) necessary for diagnosis Rotterdam Working Group. Human Reprod 2004; 19: 41-41; Fertil Steril 2004; 81: 19-25

PCOS – Prognostic important main risks - Diabetes mellitus Type 2 ( main risk, 50% ) with all its sequelae ( Macro- and Microangiopathy )

- Myocardial infarction (2-3 fold increase risk ) - Venous thromboembolism ( 5fold increase risk ) - Endometrial Cancer ( 4fold increased risk ) - Ovarian Cancer ( 2 fold increased risk ) - Breast Cancer (?)

Reasonable application of OC in the treatment of PCOS 1. All OC have benefits in all 3 key symptoms of PCOS: hyperandrogenism, cycle disturbances and ovarian changes. 2. Main mechanisms of OC are decrease of LH, increase of SHBG, with additional benefit using anti-androgenic progestogens. 3. However, all OC man increase cardiovascular risks, but different dependent on dosage and progestogen component. 4. Thus, the indication for use of OC as well as choice of OC must be decided on a very individualized basis. 5. Considering dosis and different receptor affinity, contraceptive and non-contraceptive benefits of OC should outweigh possible risks.