4 Progestin-Only Oral Contraceptives

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From: Current Clinical Practice: The Handbook of Contraception: A Guide for Practical Management Edited by: D. Shoupe and S. L. Kjos © Humana Press, Totowa, NJ

4

INTRODUCTION

Progestin-only pills (POPs) are often referred to as mini-pills. POPs contain about 35–75% of the progestin dose contained in combination oral contracep- tives (OCs) but they are taken continuously without a pill-free interval. Their effectiveness is generally similar to combination OCs. It is critical that POPs be taken at the same time every day; failure to do this may explain the higher typical- use failure rates reported in some studies. They are associated with more break- through spotting and bleeding but fewer serious side effects. Although not as well-studied as combination OCs, POPs are thought to have many of the same non-contraceptive health benefits.

MECHANISM OF ACTION

To a limited degree, POPs suppress the midcyle peak of luteinizing and fol- licle-stimulating hormone, and are only able to suppress ovulation in about half of the cycles during use. POPs have multiple other actions that prevent preg- nancy including the following:

Progestin-Only Oral Contraceptives

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• Produce “hostile” cervical mucus—making it viscid, thick, and scanty, thus preventing sperm penetration. Some reports indicate that the cervical mucus becomes so impermeable to sperm that a back-up contraception method is not needed until three consecutive pills are missed (1).

• Reduce cilia motion in the fallopian tube and decrease motility of the uterus and oviduct, thus inhibiting ova and sperm transport.

• Reducing the size and number of endometrial glands, thus inhibiting implantation.

CLINICAL EFFECTIVENESS

With perfect use, the pregnancy rate for POP users is only slightly higher than that seen with perfect use of combination OCs (0.5% versus 0.2–0.3%). For typical use, the effectiveness rate is generally around 92–95%, although different studies report significant variations. These variations likely result from differ- ences in a study population’s ability to adhere to the strict criteria of taking the POP at the same time each day. In a study of 358 obviously very compliant women using POPs, the pearl index was 0.2 per 100 woman-years (2). Other clinical studies report failure rates as high as 13% (1). Having a back-up method for cycles in which pills are missed or ensuring easy access to emergency con- traception is recommended, especially for the first 6 months of use.

Women with lower fecundity, such as breastfeeding women or women over 40 years of age, are ideal candidates for POPs. A nearly 100% effectiveness rate was reported in as study of postpartum lactating women (3).

Recent studies have showed that women with the highest body weight have the highest failure rates, although the differences are small.

ADVANTAGES OF POPs

POPs are a good option for many women for whom estrogen is contraindi- cated. POPs are generally safer and not linked to many of the serious side effects of combination OCs, such as thrombophlebitis and pulmonary embolism (1,4).

POPs are a good option in women over age 35 who smoke.

• POPs are rapidly reversible.

• Decreased risk of ectopic pregnancy (although as many as 10% of pregnancies that do occur may be ectopic) (5).

• Easy to use because the user takes the same pill every day with no break.

• More sexual freedom because taking the POP does not interfere with sexual relationships.

• Less menstrual blood flow.

• Less menstrual cramping.

Although not well-studied, the non-contraceptive health benefits of POPs

may include:

• Decreased menstrual blood loss.

B Lowered risk of anemia.

• Decreased dysmenorrhea.

• Decreased cyclic mood changes or other premenstrual syndrome problems.

• Lowered risk of benign breast disease.

• Protection from endometrial cancer.

• Decreased pain from endometriosis.

• Decreased pelvic inflammatory disease (from thickened, impenetrable cervical mucus).

DISADVANTAGES OF POPs

Unlike combination OCs, POPs must be taken at the same time each day with no pill-free interval. The following disadvantages and risks are associated with the use of POPs:

• Functional ovarian cysts are slightly more common in POP users compared with users of combination OCs.

• Pregnancies (method failures) that occur are more likely to be ectopic pregnan- cies (this a concern in heavier patients in which method failure may be higher).

• All progestin-only methods are associated with irregular bleeding (6).

B Breakthrough bleeding/spotting may account for 10–25% of POP users dis- continuing use during the first year.

B POPs have a higher number of spotting/bleeding days than combination OCs.

• Minor side effects include:

B Headache, breast tenderness, and nausea.

B Androgenic side effects, such as acne or hirsutism.

• Weight gain has been a concern but is generally not a significant problem in POP users (very low dose of progestin in POPs).

• There is no protection from sexually transmitted infections (STI) or HIV.

• Critical necessity to take the pill at the same time everyday.

• Contraceptive efficacy may be decreased substantially by other medications that induce liver enzymes.

• Less information available than for combination OCs.

B There is limited data from large-scale population studies available and lim- ited data to establish a risk–benefit profile.

CONTRAINDICATIONS TO USE

POPs are safe for the majority of women of reproductive age, although there

are certain absolute contraindications. The number of absolute contraindications

is much smaller than the list for combination OCs.

• Pregnancy or suspected pregnancy.

• Current or history of breast cancer.

• Undiagnosed genital bleeding.

• Acute liver disease.

B Hepatic adenomas/carcinoma.

• Hypersensitivity to any component of the pill.

A relative contraindication would be current coronary artery disease or cere- brovascular disease. As discussed in Chapter 15, use of POPs in women with cardiovascular disease must be individualized. A risk–benefit analysis, informed decision, and proper follow-up are advised.

EVALUATIONS, PATIENT SELECTION, AND COUNSELING When evaluating a potential POP user, the following may be considered.

These are very similar to the issues covered when evaluating a potential combi- nation OC user.

• Current gynecological issues:

B Sexual history, risk of STI exposure.

B Present and future fertility plans.

B Bleeding problems, fibroids, endometriosis.

• Demographics.

B Age, smoking status.

• Current problems, medical illnesses.

B Medications taken.

• Physical and pelvic examination.

B Blood pressure, weight.

• Laboratory assays.

B Pap test.

B Cervical tests for sexually transmitted diseases as indicated (rarely necessary for a patient in a mutually monogamous relationship).

B Screening for anemia or abnormal lipids as indicated.

Good Candidates

The following are generally suitable candidates for POP use:

• Many women for whom estrogen is contraindicated because POPs have little or no effect on clotting factors.

• Many women over 35 or 40 years of age who are not candidates or are poor candidates for combination OCs.

B Smokers.

B Multiple cardiovascular disease risk factors (Chapter 15).

 Obese with risk factors.

B Migraines.

B Sickle cell disease (

• Breastfeeding women (POPs have little or no effect on production of breast milk).

• Women who experience problems with combination OCs including:

B Headaches.

B Decreased libido.

B Breast tenderness.

B Nausea or gastrointestinal upset.

• Women on sodium valproate and benzodiazepines (they do not reduce POP contraceptive effectiveness).

Poor Candidates

• Women on enzyme-inducing drugs, such as phenytoin, barbiturates, or carbam- azepine, because there is a significant risk of reduced contraceptive effectiveness and caution advised (includes rifampicin, phenytoin, primidone, topiramate, oxcarbazepine, and griseofulvin).

• Adolescents or adults who are unable or unwilling to be rigidly compliant.

• Obese (160 lb) women (pill may be less effective, although a risk–benefit analy- sis is advised); older patients have lower fecundity and this may be taken into consideration.

COUNSELING TIPS

• POPs must be taken at the same time everyday (ideally within 1 hour, but within 3 hours is acceptable).

B Never miss any days.

B On initiation, the very first pill is taken on the first day of normal menses (or in some cases after a negative pregnancy test, when appropriate).

• Abnormal, unpredictable bleeding may be expected.

B Bleeding patterns may improve over time.

• Minor side effects, such as nausea or mood changes may decrease after several cycles.

B Premenstrual syndrome symptoms may improve or worsen.

• Have a back-up method available for missed pill days or abstain from sexual intercourse for specific time period as detailed below.

• If a pill is missed or if taken late, have a back-up method available or abstain from sex for the period of time as detailed below.

B If a pill is missed, it should be taken as soon as possible and a back-up method should be used until 7 days of uninterrupted POP use has been completed.

B If a pill is taken more than 3 hours late, a back-up method should be used for 2 days.

B If two pills are missed, back-up contraception should be used for one cycle.

• Information or access to emergency contraception may be useful to some users.

• POPs offer no protection from STIs or HIV but may provide some protection from pelvic inflammatory disease (upper tract infections).

B Adding the use of condoms advisable if a patient at risk of exposure to STIs or HIV.

• Some women may ovulate during POP use.

B Women with regular menstrual cycles during POP use may be at slightly higher risk for method failure. If these women suddenly miss a menstrual period, they should get a pregnancy test and appropriate follow-up.

WARNING SIGNS

POP users should return to their clinic or contact their health care provider for any of the following:

• Pelvic/lower abdominal pain: rule out ectopic pregnancy (ectopic pregnancy is rare, but if patient has a positive pregnancy test, an ectopic must be ruled out).

• Heavy, continuous bleeding: rule out anemia.

• A sudden skipped period or onset of amenorrhea, especially after a pattern of regular bleeding cycles: rule out pregnancy.

• Jaundice, light stools.

• The same warning signs are appropriate for POPs as combination OCs, although many of the serious side effects are not common.

OPTIONS AVAILABLE

There are seven POPs containing 0.35 mg of norethindrone and one pill con- taining 0.075 mg norgestrel on the market (Table 1). All POPs are taken every

Table 1 Progestin-Only Pills

Active pills

Progestin Product Progestin content per cycle Manufacturer

Levonorgestrel Ovrette^® Levonorgestrel 28 Wyeth

0.075 mg

Norethindrone Micronor^® Norethindrone 28 Janssen-Cilag 0.35 mg

Camila^® 28 Barr

Errin^® 28 Barr

Nor-QD^® 28 Watson

Jolivette^® 28 Watson

Nora-BE^® 28 Watson

Ortho-Micronor^® 28 Ortho-McNeil

day at the same time of day with no pill-free days. The cost of mini-pills is generally slightly higher than combined OCs regardless of the coverage.

REFERENCES

1. McCann MF, Potter LS. (1994) Progestin-only contraception: a comprehensive review.

Contraception 50:S1–S195.

2. Broome M, Fotherby K. (1990) Clinical experience with the progestin-only pill. Contracep- tion 42:489–495.

3. Moggia AV, Harria GS, Dunson TR, et al. (1991) A comparative study of a progestin-only oral contraceptive versus non-hormonal methods in lactating women in Buenos Aires, Ar- gentina. Contraception 44:31–43.

4. Vessey MP, Lawless M, Yeates D, McPherson K. (1985) Progestin-only oral contraception:

findings in a large prospective study with special reference to effectiveness. Br J Fam Plann 10:117–121.

5. Speroff L, Darney PD. (2001) A Clinical Guide for Contraception, 3rd ed. Philadelphia:

Lippincott Williams & Wilkins.

6. D’Arcangues C. (2000) Management of vaginal bleeding irregularities induced by proges- tin-only contraceptives. Hum Reprod 15:24–29.

7. Bailey P, Sanfilippo JS. (1993) Contraception in the adolescent. In: Shoupe DS, Haseltine FP, eds, Contraception. New York: Springer-Verlag, pp. 93–111.