Hormonal Contraceptives

Abbreviations

BMI = body mass index

CHC = combined estrogen/progestin contraceptive

COC = combined oral contraceptive

CVD = cardiovascular disease

DVT = deep vein thrombosis

MI = myocardial infarction

OC = oral contraceptive

PE = Pulmonary embolism

POC = progestin-only contraceptive

VTE = venous thromboembolism

Description

Background:

  • According to the World Health Organization, there is an unmet need for contraception. The need is highest among adolescent and socioeconomically disadvantaged people.
  • Estimated that 40% of all pregnancies in Canada are unplanned - half of these are carried to term, the other half terminated. 
  • Unintended pregnancies increase the risk for poor maternal and infant outcome
  • The Society of Obstetricians and Gynaecologist of Canada guidelines (2015) state it is feasible and safe for contraceptives and family planning services to be provided by trained allied health professionals such as pharmacists.

Pathophysiology:

  • Combined hormonal contraceptives (CHCs) - oral, transdermal and vaginal:
    • Inhibit follicular development and ovulation – primary mechanism
    • Thicken cervical mucus - decreases sperm penetration
    • Reduce tubal motility – interferes with fertilization
    • Endometrial changes – inhibit implantation

  • Progestin-only oral contraceptives (POCs):
    • Thicken cervical mucus – primary mechanism
    • Reduce sperm motility
    • May inhibit ovulation
       
  • Hormonal contraceptives are NOT abortifacient; established pregnancies will not be terminated.

  • Effectiveness: With typical use, if 100 women use OCs for a year, 5 to 9 will become pregnant; with perfect use, 1 would become pregnant.

For more information, go to:

Patient assessment
  • Ask the patient if she would like to become pregnant in the next year - if no, emphasize benefits of Long-Acting Reversible Contraception (LARC) i.e., IUDs, injectable medroxyprogesterone
  • Hormonal contraceptives can be safely provided to most healthy women after a careful medical history and blood pressure measurement.  Before prescribing:  

    • Assess the patient’s medical history
      • Cardiovascular risk factors:
        • Smoker
        • Obesity (BMI >30kg/m2)
        • History of MI, stroke or VTE
        • Hypertension (controlled?)
        • Dyslipidemia
        • Diabetes (controlled?)
        • Migraine (with or without aura?)
      • Breast cancer history
      • Liver function
      • Other chronic medical conditions e.g. inflammatory bowel disease, lupus erythematosus
      • Signs or symptoms of other conditions?
    • Ask about current medication use: Rx, OTC, herbal
    • Previous contraceptive use and satisfaction with method.
    • Measure patient’s blood pressure (BP
      • CHCs may increase BP
      • If  BP > 140/90, CHCs may not be the best option; discuss other contraceptive options and/or refer the patient
      • Ensure proper blood pressure measuring technique is used.  See CHEP guidelines 
    • Measure patient’s weight
      • There is conflicting evidence regarding an increased risk of pregnancy in overweight or obese women on CHCs
      • Risk of thromboembolism increased in obese patients
      • Serves as reference value to assess weight gain as a side effect of CHCs
When to Refer

1) Contraindications to combined hormonal contraceptives. Patients with ANY of the following should be advised to see their doctor to discuss other contraceptive options for routine use.

  • Breast cancer (current or past) or hormone-dependent cancer
    • CHCs may raise risk of breast cancer; concern for those with history of breast cancer.
  • Cerebrovascular disease
    • CHCs can increase risks of clots leading to stroke; concern for those with stroke history or risk factors for a stroke (hypertension, smoker, diabetes, overweight).
  • History of or current MI or ischemic heart disease, vascular disease
    • CHCs can increase risks of clots leading to MI; concern for those with MI history or risk factors for a MI (angina, hypertension, smoker, diabetes, overweight, dyslipidemia).
  • Uncontrolled hypertension (SBP ≥160 mm Hg or DBP ≥100 mm Hg)
    • Uncontrolled hypertension increases risk of MI or stroke; adding CHCs will increase this risk.
  • Complicated valvular heart disease  (e.g. pulmonary hypertension, atrial fibrillation)
    • Increases risk of MI or stroke; adding CHCs will increase that risk.
  • Current or past history of venous thromboembolism or pulmonary embolism
    • CHCs can increase risk of developing a VTE or PE; higher risk in those with history of VTE or PE.
  • Thrombophilias
    • Includes factor V Leiden, prothrombin mutation, protein S, protein C and antithrombin deficiencies or other known coagulation-factor deficiency
    • Using CHCs in these conditions greatly increases risk of developing a venous thromboembolism (VTE) or pulmonary embolism(PE).
  • Diabetes with microvascular complications
    • Microvascular complications (eg., retinopathy, neuropathy, nephropathy) are risk factors for developing an arterial thrombus, leading to MI or stroke; increased risk with CHCs.
  • <6 weeks postpartum - Immediately postpartum there is an increased risk of developing a VTE or PE (~30x risk of baseline); using CHCs in this period will increase the risk. Progestin-only contraception may be considered for non-breastfeeding women during this period.
  • Migraines with aura at any age
    • Migraine with aura is associated with higher risk of stroke.  Using CHCs may increase this risk (2-4x higher than those who have migraines with aura but do not use CHCs).
  • Migraines without aura if >35
    • Migraines without aura but age >35 years is considered a significant risk factor for stroke. These patients should be referred.
    • This does not apply to patients with non-migrainous headaches, or migraine without aura if <35 years of age.
  • Inflammatory bowel disease (IBD)
    • Associated with an increased risk of clots.
    • Uncontrolled IBD may interfere with absorption of OCs, reducing effectiveness.
    • Conflicting evidence CHCs may exacerbate IBD (?)
  • Systemic lupus erythematosus (SLE)
    • Avoid CHCs if SLE disease activity high; increased risk of thromboembolism
    • Likely safe if disease activity is stable and the patient is negative for anti-phospholipid antibodies.
  • Severe cirrhosis, liver tumour, or acute viral hepatitis flare
    • Concerns for further liver damage or reduced efficacy of CHCs.
    • Mild (compensated) cirrhosis poses no risk.
    • Carriers of viral hepatitis or those with chronic, stable disease pose no risk
  • Undiagnosed vaginal bleeding
    • Using CHCs will not worsen any cause of vaginal bleeding, but this may be a symptom of a serious condition and requires futher investigation, so referral is necessary.
  • Smoker >35 years of age (≥15 cigarettes/day)
    • Increases risk of MI significantly.
    • If <15 cigarettes/day, may consider CHCs if no other risk factors, but other methods are preferable.
  • Active cancer
    • Active cancer increases risk of VTE due to the pro-coagulant effect of tumours.
  • Medications which significantly reduce contraceptive efficacy
    • Antibiotics
      • Only rifampin significantly reduces CHC effectiveness due to enzyme inhibition.
      • Other antibiotics DO NOT cause CHC failure.  However, vomiting or diarrhea caused by the antibiotic or illness may reduce CHC efficacy, so backup methods should be recommended in those cases.
    • Enzyme-inducing antiepileptics
      • Lamotrigine, carbamazepine, phenobarbital, phenytoin, topiramate, primidone, oxcarbazepine.
    • Enzyme-inducing antiretrovirals
      • Ritonavir, efavirenz, nevirapine
      • Other antiretrovirals can be used concomitantly
    • St. John’s wort

2) Conditions in which the benefits of CHCs generally outweigh risks but caution is advised. Consider referral if the patient has more than one of the following:

  • Age over 40 years
  • Overweight, obesity (BMI >30 kg/m2)
  • Smoker (any amount) under 35 years if age
  • Diabetes (controlled)
  • Dyslipidemia
  • Migraine without aura under 35 years of age
  • Blood pressure >140/90

3)  Contraindications to progestin-only contraceptives

  • Active liver disease or history of/or actual benign or malignant liver tumours
  • Breast cancer
  • Undiagnosed abnormal vaginal bleeding

Progestin-only preparations for contraception are not associated with an increased risk of thromboembolism.

Treatment

 1) Non-prescription contraceptive options

  • Failure rates with typical use over a year
    • Male condoms (11-16%)
    • Diaphragm (15%)
    • Sponge (16-30%)
    • Female condoms (20%)
    • Spermicide alone (30%)

  • Condoms provide protection against STIs

2) Prescription options

  • Patients should be counselled about the advantages and disadvantages of long-acting reversible contraceptives (copper IUD, levonorgestrel-eluting IUDs, depo-medroxyprogresterone injection). If a long-acting contraceptive is preferred, refer the patient to her doctor or nurse practitioner

  • Pharmacists may prescribe an initial 2 month trial of a CHC (3 months if Seasonale or Seasonique), patch, vaginal ring or POC.  If tolerated, the prescription can be refilled for 1 year.  Reassess after 1 year

  • A) Oral contraceptives
    • Combined oral contraceptives (COCs) contain estrogen (ethinyl estradiol) and various progestins (See list in Product section)

    • Progestin only oral contraceptives (POCs) - the only product available in Canada contains norethindrone 0.35 mg

    • The various COCs and POCs are equally efficacious

    • Differences between COCs and POCs:
      • POCs are taken daily with no hormone-free period
      • POCs must be taken at the same time each day (within a 3 hour window)
      • POCs are associated with increased spotting and bleeding irregularities as compared with COCs 

    • Choice will be based on patient preference and previous use history
      • If patient has no preference or previous experience with hormonal contraceptives, consider a product with low estrogen content (20mcg) to minimize safety issues
      • For a breastfeeding woman, a progestin-only product is preferred

    • If patient has experienced problems on a previous COC, refer to chart in Adverse Effects below to guide product selection.

    • Options for starting COCs:
      1. First day of period start - no backup protection for pregnancy required
      2. Quick start - first tablet taken immediately - back-up protection required for 7 days
      3. Sunday start - first tablet taken on the first Sunday following the start of the patient’s period. If period starts on a Sunday, the tablet is taken that day. Back-up protection is required for 7 days unless period started on the Sunday the COC was started

    • POCs can be started on any day of cycle. If not the first day of the patient's period, a back-up method of protection must be used for 48 hours

    • If starting contraceptives after emergency contraception(EC):
      • After levonorgestrel:
        • COC - start the day of or the day after EC + barrier method of contraception for first 7 days
        • POC - start the day of or the day after EC + barrier method of contraception for first 2 days
      • After ulipristal acetate:
        • Start OC five days after EC + barrier method of contraception beginning immediately after EC and for first 14 days of OC

    • Major adverse effects of COCs (rare):
      • Cardiovascular events: DVT, MI, stroke, retinal artery thrombosis
      • Benign liver tumour
      • Gallbladder disease
      • Hypertension
      • Exacerbation of systemic lupus erythematosus

    • Minor adverse effects: these can often be managed by changing the dose or relative proportions of estrogen and progestin as outlined in the following table:

Problem

Reason

Management

  • Early bleeding or spotting (days 1-9 of cycle)
  • Continuous bleeding or spotting
  • No withdrawal bleeding
  • Vasomotor symptoms

Low estrogen

  • Higher estrogen content (30-35 mcg)
  • Late cycle bleeding and spotting (days 10-21)
  • Delayed withdrawal bleeding

Low progestin

  • Higher progestin content
  • Monophasic products
  • Bloating or edema
  • Headache that has predictable timing
  • Dizziness
  • Nausea
  • Visual changes that have predictable timing
  • Leg cramps
  • Hypermenorrhea, menorrhagia

High estrogen

and/or

Low progestin

  • Lower estrogen content (10-20 mcg)
  • Higher progestin content
  • Monophasic products
  • Hypermenorrhea, menorrhagia, clotting
  • Dysmenorrhea
  • Increased breast size
  • Hypertension
  • Urinary tract infections

High estrogen

  • Lower estrogen content
  • Depression
  • Fatigue
  • Breast tenderness
  • Libido decrease
  • Weight gain
  • Increased appetite
  • Dizziness

High progestin

  • Lower progestin content
  • Phasic products
  • Libido increase
  • Edema
  • Oily skin and scalp
  • Acne
  • Hirsutism

High androgen

  • Lower androgenic activity (eg. 3rd and 4th generation COCs – see product chart)

Adapted from RxFiles, 10th edition, Hormonal Contraception Chart

  • B) Transdermal or intra-vaginal estrogen
    • Same efficacy as oral contraceptives
    • Main advantage of transdermal or intra-vaginal estrogen over oral contraceptives: daily action not required, may enhance compliance in some patients leading to better efficacy (however, real-world failure rates are similar with both)
    • Contraindications and side-effects similar to combined oral contraceptives

    • Transdermal patch (Evra):
      • Releases estradiol 35mcg and norelgestromin 200mcg per day
      • Change patch once weekly for 3 weeks, followed by one week off.  May use consecutively, without a hormone-free interval, for 9-12 weeks
      • Initiate on 1st day of menses, or 1st Sunday after menses begins.  7 days of backup method recommended
      • Possibly higher spotting rate and breast symptoms compared to oral contraceptives
      • If weight >90 kg, lowered effectiveness and increased clot risk

    • Vaginal ring (Nuvaring):
      • Releases estradiol 15mcg and etonogestrel 120mcg per day
      • Ring left in place for 3 weeks, followed by 1 week hormone-free interval
      • Insert between day 1-5 of cycle.  7 days of backup method recommended
      • Less irregular bleeding compared to oral contraceptives in first cycle
      • May cause a foreign body sensation, discomfort, or coital problems
General Advice / Monitoring
  • Birth control pills will not be harmful in the event that emergency contraception failed and the patient is pregnant
  • Birth control pills do not protect against sexually transmitted infections. Recommend use of condoms in addition to birth control pills if STIs are a concern
  • Importance of adherence and what to do about missed doses (suggest giving the patient a printout)
    • Combined OCs (other than Seasonale and Seasonique)
      • If pill delayed less than 24 hours at any point:  Take 1 pill immediately, then again at the regularly scheduled time.  May mean taking two pills on the same day
      • Week 1:
        • If 1 or more pills are missed, take 1 pill immediately and continue until end of pack.  Skip pill-free period and start a new pack.  Use a backup method of contraception for 7 days and consider EC if intercourse in past 5 days
      • Week 2 or 3
        • <3 pills missed: take 1 pill immediately and continue until end of pack; skip pill-free period and start a new pack
        • >3 pills missed: take 1 pill immediately and continue until end of pack; skip pill-free period and start a new pack.  Use backup method of contraception for 7 days. Consider EC if prolonged or repeated pill omissions

    • Seasonale and Seasonique (from their monographs):
      • If you MISS one pink “active” pill:
        • 1. Take it as soon as you remember. Take the next pill at your regular time. This means you take 2 pills in 1 day.
        • 2. You do not need to use a back-up birth-control method if you have intercourse
      • If you MISS two pink “active” pills in a row:
        • 1. Take 2 pills on the day you remember and 2 pills the next day.
        • 2. Then take 1 pill a day until you finish the pack. 
        • 3. You COULD BECOME PREGNANT if you have intercourse in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicide) as a back-up on the 7 days after you restart your pills.
      • If you MISS 3 OR MORE pink “active” pills in a row:
        • 1. Do not remove the missed pills from the pack as they will not be taken. Keep taking 1 pill every day as indicated on the pack until you have completed all of the pills in the pack. For example: if you resume taking the pill on Thursday, take the pill under “Thursday” and do not take the previous missed pills. You may experience bleeding during the week following the missed pills.
        • 2. You COULD BECOME PREGNANT if you have intercourse during the days of missed pills or during the first 7 days after you restart your pills.
        • 3. You must use a non-hormonal birth control method (such as condoms or spermicide) as a back-up when you miss pills and for the first 7 days after you restart your pills. If you miss your period when you are taking the white pills, call your healthcare professional because you may be pregnant

    • Progestin-only OCs
      • > 3 hours late in taking pill or missed > 1 pill, use back-up method of contraception for 48 hours; if unprotected intercouse in the past 5 days, EC is recommended

    • Transdermal patch
          • If patch change is delayed:
            • Week 1: Apply as soon as possible.  Switch to a new patch change day.  Use backup method of birth control for 1 week
            • Week 2 and 3:
              • 1-2 days late: Apply ASAP. No backup required and patch change day stays the same.
              • >2 days: Apply ASAP.  Start a new 4 wk cycle, with new Day 1 and new patch change day. Use backup method of contraception for 7 days
          • If patch comes off for <24h, reapply ASAP.  No loss of efficacy, and patch change day remains the same
          • If patch comes off for >24h, apply new patch. Start a new 4 wk cycle, with new Day 1 and new patch change day.  Use backup method of contraception for 7 days


    • Vaginal ring
      • If ring change is missed, has a one week window of forgiveness; eg. should be effective for 4 weeks total, though concern towards the end of the fourth week.  If ring change is missed for more than a week, consider the patient a new start (eg. backup contraception for 7 days, consider EC if intercourse in past 5 days)
      • If ring expulsion occurs and it has been < 3 hours, reinsert ring and carry on as usual
      • If ring expulsion occurs and it has been > 3 hours, consider that as a missed dose and follow these recommendations:
            • Week 1 and 2: Backup method required for 7 days after new ring in place
            • Week 3: Start new cycle and skip hormone-free interval; use backup method for 7 days and consider EC if intercourse in past 5 days


  • Significant vomiting and/or diarrhea for more than 48 hours: same precautions as missed dose(s) apply

  • Signs / symptoms of serious adverse effects  - Advise the patient to see a physician immediately if any of the following symptoms occur (nmemonic “ACHES”):
    • Abdominal pain –severe  (gallbladder disease, pancreatitis, hepatic adenoma, thrombosis)
    • Chest pain  - severe,  shortness of breath (pulmonary embolism, acute MI)
    • Headaches - severe (stroke, hypertension, migraine)
    • Eye problems – blurred vision, flashing lights, loss of sight (stroke, hypertension, vascular insufficiency)
    • Severe leg pain – calf or thigh (DVT)

  • Minor, bothersome side-effects – advise the patient to contact pharmacist if these occur:
    • Breakthrough bleeding
      • Most common in first 3 months
      • If persists, consider changing product depending when bleeding occurs (see table under treatment section)
    • Breast tenderness
      • Most common in first 3 months
      • If persists, change to COC with less estrogen
    • Weight gain
      • Little or no weight gain caused by COCs
      • Appetite may increase in first month (lower progestin content products can reduce this)
    • Nausea
      • Should subside within 3 months
      • Take with food or at bedtime
      • If persists, choose COC with less estrogen
    • Headache
      • If headaches consistently triggered or worsened by COC, should avoid use
    • Acne
      • All COCs typically have a beneficial effect on acne, but acne may worsen during the first few months of treatment
      • Products with lower androgen content may have a greater beneficial effect on acne (eg. 3rd and 4th generation products)

  • When to expect period post-ECP and beginning birth control: If beginning COCs after taking emergency contraception, should have a period during the 7 day hormone-free interval.  Recommend a pregnancy test if no period within 4 weeks

  • With the patient’s permission, follow up to assess tolerability and adherence in 4 weeks
    • If minor side effects have occurred, provide assurance these usually resolve within three months of OC therapy
      • If the side effects are very bothersome and the patient does not want to continue with the same product, refer the patient to her doctor or contact her doctor with a recommendation for a product less likely to cause the side effect
    • Remind the patient to make an appointment with her doctor before the second OC pack is finished
    • See if patient has missed any pills and knows what to do if she does
    • Reassess possible drug interactions or any new risk factors
Products

Table 1: Oral contraceptives for pharmacist prescribing

 

Brand Names

Components (EE – Ethinyl estradiol)

Progestin -only

Micronor®

Norethindrone 0.35mg

1st Generation 

LoLo™ (24/2/2 regimen)

24 pills of:

EE 10mcg
Norethindrone 1mg

2 pills of:

EE 10mcg

Followed by 2 placebo pills

Minestrin®

 

EE 20mcg
Norethindrone 1mg

Loestrin®

EE 30mcg
Norethindrone 1.5mg

Demulen®

EE 30mcg
Ethynodiol diacetate 2mg

Brevicon® 0.5/35

Ortho® 0.5/35

EE 35mcg
Norethindrone 0.5mg

Synphasic®

EE 35mcg
Norethindrone 0.5mg x12 - 1mg x9

Brevicon® 1/35       Select™ 1/35
Ortho® 1/35

EE 35mcg
Norethindrone 1mg

Ortho® 7/7/7

EE 35mcg
Norethindrone 0.5mg x7 - 0.75mg x7 – 1mg x7

2nd Generation 

Alesse®                   ESME
Alysena™                 Lutera™

EE 20mcg
Levonorgestrel 0.1mg

Triquilar®

EE 30mcg x7; 40mcg x7; 30mcg x7
Levonorgestrel 0.05mg x7; 0.075mg x7; 0.125mg x7

Min-Ovral®            Ovima™
Portia®

EE 30mcg
Levonorgestrel 0.15mg

Seasonale®     

EE 30mcg x84 
Levonorgestrel 0.15mg x84

Seasonique®

EE 30mcg x84; EE 10mcg x7
Levonorgestrel 0.15mg x84

3rd Generation 

Marvelon®             Freya
Ortho-cept®          Mirvala™
Apri®                    Reclipsen™

EE 30mcg
Desogestrel 0.15mg

Cyclen®

EE 35mcg
Norgestimate 0.25mg

Linessa®

EE 25mcg
Desogestrel 0.1mg x7 – 0.125mg x7 – 0.15mg x7

Tri-cyclen®

EE 35mcg
Norgestimate 0.18mg x7 – 0.215mg x7 – 0.25 mg x7

Tri-cyclen® LO

EE 25mcg
Norgestimate 0.18mg x7 – 0.215mg x7 – 0.25 mg x7

4th Generation 

Yasmin®                 Zamine™
Zarah™

EE 30mcg
Drospirenone 3mg

Yaz®
Mya™

EE 20mcg
Drospirenone 3mg

(24 active pills, 4 placebo)

Yaz® Plus

EE 20mcg
Drospirenone 3mg
Levomefolate 0.45mg (folic acid supplement)

(24 active pills, 4 placebo)

*Progesterone only pill (Micronor 0.35mg) is also an option for nursing women
Some generics may not be in this list, but would still be eligible for pharmacist prescription

Table 2: Non-oral contraceptives for pharmacist prescribing

 Brand Name 

Components (EE – Ethinyl estradiol)

Nuvaring®

  EE 15mcg and etonogestrel 120mcg released daily
Evra®   EE 35mcg and norelgestromin 200mcg released daily
Prescribing and Billing Details
  • Prescribe 2 months of therapy (3 months if using Seasonale or Seasonique).
  • Can provide refills up to a year (tolerability of chosen therapy should first be established), then reasses. 
  • A medical examination is not required for renewal of a hormonal contraceptive prescription. As long as no changes of concern are identified in the patient's medication, medical and social history and no red flag symptoms are present, a prescription for another year's supply can be issued. The patient's doctor / nurse practitioner will be notified of the new prescription via the PAR and can arrange an appointment with the patient if they feel a medical evaluation is needed for any reason at that time.
  • Currently, no assessment fee will be covered by the Drug Plan. The pharmacy may choose to charge the patient for the assessment fee. PAS recommends a fee of $18.00. Note this fee cannot be charged to NIHB or NIHB clients.
  • Only products in the "product" section of this guideline are acceptable for prescribing by a pharmacist.
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Merck Manual http://www.merckmanuals.com/professional/gynecology_and_obstetrics/family_planning/oral_contraceptives.html
  2. Graves, G.  Contraception. In CTC, RxTx online databases. CPhA. Available from www.e-therapeutics.caby subscription (In Saskatchewan, through RxTx  at https://www.shirp.ca/).
  3. Oral Contraceptives.  Dynamed.  Available at https://dynamed.ebscohost.com/ by subscription. 
  4. Martin, K.  Overview of the use of estrogen-progestin contraceptives.  UpToDate.  Available at www.uptodate.com by subscription
  5. Samra-Latif, O.  Contraception.  Medscape reference.  Available at http://emedicine.medscape.com/article/1132465-overview (free access, requires registration).
  6. World Health Organization.  Medical Eligibility Criteria for Contraceptive Use.  Available at: http://whqlibdoc.who.int/publications/2010/9789241563888_eng.pdf
  7. Black A, Guilbert A. Canadian Contraception Consensus (Part 1 of 4). J Obstet Gynaecol Can 2015;37(10):S1–S28.
Written by Terry Damm, BSP and Karen Jensen, MSc, BSP.  
Posted Nov 2017