Managing Adverse Effects of Hormonal Contraceptives

pharmacy

By Pharm. Timeyin Ogungbe

Hormonal contraception refers to birth control methods that act on the endocrine system. Many contraceptives rely on the use of steroid hormones.

There are two main classes of hormonal contraceptives:

1. Combined contraceptives – contain both oestrogen (usually ethinyl estradiol) and progestin.
2. Progestogen-only contraceptives contain only progesterone or a synthetic analogue (progestin).

Mechanisms of action

Combination oral contraceptive pills

Most combination OCPs contain ethinyl estradiol (20 to 50 mcg) and a synthetic progestin (e.g,

norgestrel, norethindrone, levonorgestrel, desogestrel). These pills inhibit ovulation in most women.

They also induce thickening of the cervical mucus, which impedes transport of sperm to the uterus. With perfect use, only 0.1 per cent of women become pregnant within the first year of using a combination OCP.

Progestin-only contraceptive methods

Low dose progestogen-only contraceptives include traditional progestogen-only pills and the subdermal implant Jadelle. These contraceptives inconsistently inhibit ovulation in approximately 50 per cent of cycles and rely mainly on their progestogenic effect of thickening the cervical mucus and thereby reducing sperm viability and penetration.

Intermediate dose progestogen-only contraceptives, such as the progestogen-only pill Cerazette (or the subdermal implant Implanon), allow some follicular development but much more consistently inhibit ovulation in 97–99 per cent of cycles. The same cervical mucus changes occur as with low dose progestogens.

High dose progestogen-only contraceptives, such as the injectables Depo-Provera and Noristerat, completely inhibit follicular development and ovulation. The same cervical mucus changes occur as with very low dose and intermediate dose progestogens.

Because of the high dose of progestin, ovulation is inhibited in most women. With perfect use, only 0.3 per cent of women become pregnant within the first year of using medroxyprogesterone injections.

Managing adverse effects of hormonal contraceptives

Weight gain

Long-acting injectable depot medroxyprogesterone acetate (Depo-Provera) is the only hormonal contraceptive that is consistently associated with weight gain. A prospective study found that women who used Depo-Provera gained an average of 11.2 lb (5.1 kg) over 36 months, whereas women who used combined oral contraceptives did not gain any weight.  There are no significant differences among combined oral contraceptives in terms of weight gain. A systematic review of randomised controlled trials did not find a causal connection between combined hormonal contraceptives and weight gain, whereas a Cochrane review found the evidence to be insufficient. Extended-cycle combined oral contraceptives do not cause more weight gain than standard regimens.

Headache

Combined oral contraceptives increase the risk of stroke in women who have migraines with aura, and should not be used in these patients. A systematic review found that 10 per cent of women have new-onset headache with the use of combined oral contraceptives. The type and dose of progestin do not affect headache, nor does the particular formulation.

Headaches are more common during the first cycle of combined oral contraceptives and in women who are older than 35 years. If headache occurs in a woman who is older than 40 years during the placebo week of a 28-day regimen, the addition of 10 mcg of ethinyl estradiol for five of the seven placebo days may help. It is not known if this regimen is effective in younger women.

Continuous use of combined oral contraceptives also can be attempted. A Cochrane review comparing extended-cycle with standard 28-day regimens found slightly reduced rates of menses-associated headache in the extended-cycle group. A prospective, open-label, industry-sponsored trial found that switching from a 28-day to a 168-day regimen reduced headache and increased quality-of-life measures in patients with severe headaches, but not in those with mild headaches. Switching to a different combined oral contraceptive or taking diuretics or multivitamin supplements is not effective in treating headaches.

Breast tenderness

The use of combined oral contraceptives decreases breast tenderness after 18 months, but there are no significant differences among formulations.

Breakthrough bleeding

Breakthrough bleeding is common in the first months of combined oral contraceptive use, and patients should be reassured during this time. Variations in the oestrogen dose above 20 mcg do not alter bleeding rates, nor does changing the type of progestin. Bleeding patterns are similar among monophasic and biphasic regimens, but the evidence is insufficient to determine whether monophasic and triphasic regimens result in different bleeding patterns.

A randomised controlled trial comparing continuous use with a standard 28-day cycle found that spotting increased initially with continuous use, but was less than with the standard regimen by nine months. Increasing the oestrogen dosage from 20 to 30 mcg per day does not reduce breakthrough bleeding in extended-cycle regimens. Women on regimens containing norethindrone had significantly more days of amenorrhoea than those on levonorgestrel-containing regimens. If breakthrough bleeding occurs with extended-cycle regimens, the pills should be stopped for three or four days, then restarted.

Other bleeding irregularities

Patients often discontinue hormonal contraceptives because of menstrual cycle disorders. Progestin-only pills and low-dose combined oral contraceptives (less than 20 mcg per day) are associated with a higher incidence of bleeding disturbances. Compared with non-hormonal contraceptive methods, Depo-Provera is strongly associated with missed menstrual periods and bleeding for longer than 20 days.

A Cochrane review found that no interventions to regulate menstrual bleeding in women using Depo-Provera were useful in the long term. In women using progestin-only injectable contraceptives, short-term treatment with nonsteroidal anti-inflammatory drugs may be helpful for spotting. Nonsteroidal anti-inflammatory drugs or ethinyl estradiol can also be used for heavy or prolonged bleeding until another contraceptive method is chosen.

Women who use the single-rod etonogestrel implantable device (Implanon) should expect changes in their menstrual cycle. Before insertion, clients should be informed that only about 11 per cent of women have a normal bleeding pattern. A combination of mifepristone (Mifeprex) and ethinyl estradiol reduces the duration of a single bleeding episode in women who use Implanon, but does not alter the overall bleeding pattern.

One study showed that doxycycline shortens a single episode of bleeding in women who use Implanon, but a subsequent larger study did not confirm this finding. If abnormal bleeding persists beyond three months, an alternative contraceptive method may be considered, and the patient may need to be evaluated for other causes.

Mood

No significant differences in effect on mood have been found among various combined oral contraceptives. A prospective population-based study found that Depo-Provera was associated with a slightly increased rate of depression, which can persist after discontinuation of therapy. A prospective cohort study, however, found that neither combined oral contraceptives nor Depo-Provera was associated with an increased risk of depressive symptoms.

Sexual effects

Findings from studies of the sexual effects of hormonal contraceptives have been inconsistent, and the pharmacologic basis for these effects is unclear. Bioavailable testosterone is lower in women who use combined oral contraceptives than in nonusers; however, one review found that women who use these contraceptives show more interest in erotic images.

A prospective analysis of women using Depo-Provera found no change in sexual function after four months, and women using progestin-only pills had no difference in sexual desire compared with those receiving placebo. Another study found that there was no significant change in libido after 24 months among women using Depo-Provera, women taking an oral contraceptive containing 0.15 mg of desogestrel and 20 mcg of ethinyl estradiol, and women using non-hormonal contraception. A prospective randomised study comparing Nuvaring with two combined oral contraceptives (one containing 20 mcg of ethinyl estradiol and 100 mcg of levonorgestrel, and the other containing 15 mcg of ethinyl estradiol and 60 mcg of gestodene) found that the latter pill had the greatest negative effect on sexual desire. The reason is not known.

If adverse sexual effects persist beyond three months, the method can be changed, but there is little evidence to recommend one method over another. Because sexual function depends on many factors, other causes of sexual dysfunction should be considered before changing methods.

Skin changes

Acne can develop or worsen with the use of progestin only contraceptives. A questionnaire-based study of 161 women who used the levonorgestrel-releasing intrauterine system (Mirena) for dysfunctional uterine bleeding found that 22 per cent discontinued use secondary to progestin-associated effects (e.g., acne, oily skin, hirsutism, bloating, headaches, weight gain, depression, breast tenderness, decreased libido).

A retrospective study of Implanon users found that 11 per cent had acne after insertion.  If acne worsens with a progestin-only contraceptive, a combination method can be tried if the patient is medically eligible.

Of patients who had acne at baseline and who were using a combined oral contraceptive with 20 mcg of ethinyl estradiol and 0.15 mg of desogestrel, 70 per cent had resolution of symptoms at six months. If acne does not improve within six months of combined oral contraceptive use, it typically will not improve with continued use. A Cochrane review analysing several combined oral contraceptive regimens found that they are effective in treating acne, but that differences in effectiveness among progestins is not clear.

About 6 per cent of Depo-Provera users report new onset facial hair at six months of use. Combined oral contraceptives are used to treat hirsutism, and a small, prospective, randomised, double-blind study found that those containing levonorgestrel and desogestrel are equally effective.

Nausea

Levonorgestrel-only emergency contraceptives cause less nausea and vomiting than regimens with a combination of ethinyl estradiol and levonorgestrel. Pretreatment with metoclopramide can reduce nausea in women using combined oral contraceptives for emergency contraception. The World Health Organisation advises pre-treatment for women who have a history of nausea and vomiting with emergency contraceptive use.

Decreased breast milk

A Cochrane review found insufficient evidence that hormonal contraceptives affects breast milk quantity or quality. Combined oral contraceptives should not be used for the first six weeks postpartum because of increased risk of hypercoagulability. Progestin-only pills do not impair lactation.