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Disclosures None Hormonal Contraception: Updates and Review

Rameet H. Singh MD MPH

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Objectives New Contraceptive Vaginal Ring (CVR) 1. What's new in Hormonal Contraception? ● FDA approved 2018 2. Common medical conditions and prescribing HC. ● Annovera ● Soft, reusable, flexible 3. Review common side effects of HC and how to silicone ring manage them

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CVR - Annovera Nuva Ring vs Annovera

● Daily Release Rates ● Daily Release Rates ● 103 mg Segesterone Acetate/17.4 mg of EE ○ Etonorgestrel 120 mcg/day ○ Segesterone 150 mcg/day ○ EE 15 mcg/day ○ EE 13 mcg/day ● Release 0.15 mg/day of SA ● Diameter 54 mm ● Diameter 56 mm ● Thickness 4 mm ● Thickness 8.4 mm ● Release 0.013 mg/day of EE ● Lifespan 1 cycle ● Lifespan 13 cycles ● Refrigeration ● No refrigeration

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Annovera - Effects on Vaginal Flora Annovera - Effects on Vaginal Flora

● Vaginal flora can be disrupted by ○ Hormonal fluctuations Sustained use did ○ Sexual activity (frequency/# partners) not increase vaginal ○ Use of vaginal products infections or disrupt ○ Antibiotics vaginal flora ○ Douching

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Annovera - Patient counseling Vagainal Ring - Annovera ● 2308 women ● Leave in place for 21 days and then remove for 7 days ● Ages 18 - 40 years ● Wash with mild soap. Store in case away from sunlight. ● ⧬ BMI > 29 kg/m² ● ⧬ < 35 years ● Anticipatory guidance ○ Perfect use failure rate 2.98 pregnancies per 100 ○ Ring can be left in place during sex couples per year ○ Does not need frequent washing ○ Typical use failure rates not yet published ○ Does not increase vaginal infections

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Vagainal Ring - Annovera - Side effects Vaginal Ring - Annovera ● 89% satisfaction rate related to ● Anticipated availability - third quarter of 2019 ○ Ease of use ○ Side-effects ● Reduced pricing planned for Title X clinics ○ Expulsions ○ feeling the product and effects during sexual activity ● Developed by the Population Council ● 5-10% experienced unscheduled bleeding per 28-day cycle ● Licensed to Therapeutics MD ● “The first woman-controlled, procedure-free, long-acting reversible contraceptive (LARC).”

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Antibiotics and Hormonal Contraception (HC) Misconceptions/Myth Old methods - new updates ● Back up contraception necessary ● May interrupt a woman’s use of HC or ● Poor compliance with antibiotics

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Antibiotics and Hormonal Contraception (HC) Antibiotics and HC - Take Home

● 2018 Systematic Review ● Existing evidence does not support drug interactions ● 29 studies that examined HC and non-rifamycin antibiotics between HC and non-rifamycin antibiotics ○ Pregnancy rates ● Women using broad spectrum antibiotics are eligible to ○ Serum progesterone levels use all contraceptive methods ○ Sonographic evidence of ovulation ● Providers should encourage correct and consistent use ○ Change in bleeding in patterns or ○ Pharmacokinetics of HC at all times, including during illness

Simmons KB, Haddad LB, Nanda K, Curtis KM. Drug-interactions between non-rifamycin antibiotics and hormonal contraception: A systematic review. Am J Obstet Gynecol 2018, 218:88-97 15 16

Breast Cancer and HC Breast Cancer and HC

● Little is known about whether contemporary hormonal ● NEJM 2017 contraception is associated with an increased risk of ● Methods breast cancer ➢ Nationwide registries – followed Danish women 15-49 ● NEJM 2017 ➢ Cohort study of 1.8 million women ➢ Cohort study of 1.8 million women ➢ Followed for 10.9 years ➢ Followed for 10.9 years

Mørch LS, Skovlund CW, Hannaford PC et al. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med December, 2017; Mørch LS, Skovlund CW, Hannaford PC et al. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med December, 2017; 377(23): 2228-2239. 377(23): 2228-2239.

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Breast Cancer and HC Breast Cancer and HC – Take Home ● Results ➢ 19.6 million person-years of data ● Overall risk of Breast cancer is low ➢ 11, 000 breast cancer diagnoses ● Increased risk in recent studies equates to 1 additional case ➢ RR of Breast cancer among current or recent users of HC of breast cancer for every 7690 women using HC compared to never users – 1.20 (95% CI, 1.14 -1.26) ● Benefits of HC include: ➢ Decreased risk of ovarian, endometrial, and colorectal cancer ➢ Risk increased with duration of use RR 1.09 (95% CI, ➢ Pregnancy and maternal mortality riskier than Breast CA 0.96– 1.23) ➢ Socioeconomic benefits

Mørch LS, Skovlund CW, Hannaford PC et al. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med December, 2017; 377(23): 2228-2239. 19 20

Nocebo Phenomenon Menstrual Related Side Effects

● Counseling about side-effects from OCPs and including ● Absent or Decreased Scheduled bleeding

them in the product label, is ○ Scant bleeding or spotting counts

“unwarranted and probably unethical” ○ Complete amenorrhea – formulation, duration

● Placebo-controlled randomized trials show no difference ● Unscheduled Vaginal Spotting or Bleeding

in side-effects ○ 30-50% first few months

● If women are told to expect noxious side effects ○ 10-30% by third pack

○ they may occur due to the power of suggestion ○ Rule out pregnancy, infection, missed pills, medications

○ Or may reflect prevalence of side-effects in the population and GI problems

○ Change pills after 2-3 months if persistent

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Estrogen Related Progesterone Related Androgen Related Weight gain in breast, hips, and Cyclic weight gain Slow, steady, weight thighs gain Cervical eversion or ectopy Hypoglycemic headaches Hirsuitism Increased blood pressure Constipation, bloating Rise in gallbladder cholesterol Fatigue Elevated LDC-C Combined Oral Contraceptives Melasma, telangiectasia Depressive symptoms Acne Hepatocellular adenoma Increased insulin resistance Oily skin Estrogen, Progesterone and combined effects Arterial thrombosis Precipitation of gallbladder sludge or stones Venous thromboembolism Headaches Nausea Increased HDL-C and triglycerides Mastalgia Nausea Mastalgia

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Unscheduled Bleeding Management Unscheduled Bleeding Management

● Bleeding before completing active pills ● Continued spotting/bleeding after scheduled bleeding ○ Need more endometrial support ➢ Need more building up of endometrium

○ Increase progestin content ○ Increase estrogen in the first pills of the pack

○ Different monophasic or triphasic with increasing ○ Decrease progesterone in the first pills of the pack progestin

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Unscheduled Bleeding Management COC – Weight Changes

● Mid cycle spotting/bleeding ● Women may respond robustly to any of the pill’s hormones ○ Unclear etiology ● Increases in size of breasts, hips and thighs – ○ Use triphasic pill that increases both Estrogen effect on adipose cells (hypertrophy) estrogen/progesterone

○ Decreasing estrogen can reduce this impact

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COC – Weight Changes COC – Headaches

● Weight gain similar to premenstrual fluid ● 4% of COC users stop due to HA retention is due to increased aldosterone release ● RCT found that women using placebo pills – Estrogen activity augmented by progesterone experienced headaches as frequently as COC users

○ Decrease both estrogen and progesterone ● HA complaints decrease with continued use ○ Choose drosperinone

● Encourage women to adopt a healthy diet and exercise

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COC – Headaches COC – Headaches

● HA with first cycle ● Confirm whether HA started or worsened in - 1 in 3 chance of having them in the 2nd month frequency or severity with onset of COC use - 1 in 10 by 3rd month - Stop COC during evaluation if HA severe or aura - Consider POPs • No evidence to support the common clinical practice of switching pills to treat HA - Consider lowering estrogen dose

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COC – Headaches COC – Skin Changes

● Rule out other causes ● Estrogen stimulates melanocytes

○ BP ○ Darkening of pigmented areas – linea nigra

○ Caffeine intake ○ Dark patches on the face – melasma or chloasma

○ TMJ, sinusitis, dental problems, drug or alcohol use, etc ○ Women with darker skin are more susceptible

● Characterize type of HA ○ D/C estrogen – will fade but sometimes incompletely

○ New onset migraines or worsening severity during active ○ Consider POPs if woman gives previous history of this

pills STOP ○ Sunscreen and hats

○ Aura – STOP

○ HA during placebo pills – offer extended use COCs 33 34

COC – Skin Changes COC – Skin Changes

● Estrogen stimulates formation of Telangiectasias ● Worsening or new onset acne, oily skin or hirsuitism

○ Fine, dilated intracutaneous capillaries and small arteries ○ Less than 5% of women

○ Not clinically significant ○ Consider other causes if symptoms are severe (ovarian) ○ May be cosmetically disturbing ○ Switch to a COC that is less androgenic ○ Avoid in women with pre-existing T ○ In one study Drosperinone superior to norgestimate

○ If none available pick one with low androgenicity and high estrogen content

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COC – Mastalgia COC – Mastalgia

● Both estrogen and progesterone affect the breast ● Estrogen

● 30% of women experience Mastalgia when starting - hypertrophy of the adipose cells in the breast Ocs - breast size can increase

● Ovulating women experience a substantial increase ● Interventions in breast volume (up to 20%) during the luteal phase ○ Proper fitting bra due to venous and lymphatic engorgement ○ Decrease doses of both

○ Low dose 20 mcg E less mastalgia than 35 mcg

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COC – GI Symptoms COC – GI Symptoms

● Estrogen can induce nausea/vomiting ● Most women will get used to the pills and symptoms

● Sex steroids affect the intrinsic firing rate of the resolve in 1-3 months

gastric pacemaker cells ● Take pills at night or with food

● Progesterone – slows peristalsis ● For missed pills – take them 12 hours apart instead

○ Increased constipation of double dosing

○ Increased sensation of bloating and distension

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COC – GI Symptoms COC – Eyes

● Advise more fluids, fresh fruit and vegetables ● May notice visual changes or change in lens

● If recent onset severe GI symptoms tolerance with COC due to dry eyes

○ Evaluate for cholecystitis, appendicitis, diverticulitis, ● Normal saline drops can help reactivation of IBS

● If no resolution

○ Switch to POP

○ Decrease hormone dose. Can go as low as 10 mcg now.

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COC – Mood Swings and Depression COC – Mood Swings and Depression

● Based on multiple studies – no increased risk of clinical depression ● Some women report increase in depressive ● Estrogen and Progestin in high-dose pills interact symptoms, moodiness and other emotional states on with tryptophans and serotonin – NOT with low COCs dose pills ○ Evaluate when in the cycle these present

● Some women report increase in depressive ○ May be an idiosyncratic response to hormones symptoms, moodiness and other emotional stats on COCs 43 44

COC – Mood Swings and Depression

● If symptoms before menses – extended or continuous COC – Mood use of active pills Swings and ○ If wants period – start active pills on first day of menses Depression ● May respond to decrease in hormone dose or stopping

● Consider drospirenone containing - FDA approved for PMDD

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COC – Libido COC – Libido

● During reproductive years libido not associated with ● COCs decrease vaginal secretions by decreasing circulating testosterone cervical secretions

● RCTs have found that few women complain of change ○ May be interpreted as decreased arousal

in libido ○ Decreased sections may make intercourse painful

● Libido – affected by relationship issues, personal ○ Consider increasing estrogen or vaginal ring history, stress, depression etc ○ Switch to a more androgenic pill

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Questions? Thank you!

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