Perimenopausal women have low fertility but must still be advised to use contraception until natural sterility is reached if they are sexually active. Patterns of contraceptive use vary in different countries worldwide. Long-acting reversible contraceptive methods offer reliable contraception that may be an alternative to sterilisation. Hormonal methods confer significant non-contraceptive benefits, and each individual woman should weigh up the benefits and risks of a particular method. No method of contraception is contraindicated by age alone, although combined hormonal contraception and injectable progestogens are not recommended for women over the age of 50 years. The intrauterine system has particular advantages as a low-dose method of effective hormonal contraception, which also offers control of menstrual dysfunction and endometrial protection in women requiring oestrogen replacement. Condoms are recommended for personal protection against sexually transmitted infections in new relationships. Standard hormone replacement therapy is not a method of contraception.
Fertility in the perimenopause
The perimenopause represents the transitional years before the last spontaneous menstruation. Fertility gradually declines with age, as oocytes become more susceptible to aneuploidy and mitochondrial mutations and anovulatory menstrual cycles increase in frequency. Spontaneous pregnancy over the age of 50 years is relatively rare.
Women are, however, still potentially fertile during the perimenopause and many continue to be sexually active. A recent UK survey showed that many individuals remained sexually active long into later life, and women aged 45–54 years had an average of 3.5 episodes of sexual intercourse in the previous 4 weeks .
Pregnancy in the perimenopause
In the UK, the conception rate for women aged 40 years and over increased from 6.6 conceptions per thousand women in 1990 to 13.9 per thousand in 2011, as women increasingly chose to have children later . For women aged 40 years and over, the percentage of conceptions leading to therapeutic abortion fell from 43% in 1990 to 28% in 2011 . Significant numbers of pregnancies in women over 40 years remain unplanned: review of 2006 data from the US puts this figure at 48% .
Pregnancy in the perimenopause
In the UK, the conception rate for women aged 40 years and over increased from 6.6 conceptions per thousand women in 1990 to 13.9 per thousand in 2011, as women increasingly chose to have children later . For women aged 40 years and over, the percentage of conceptions leading to therapeutic abortion fell from 43% in 1990 to 28% in 2011 . Significant numbers of pregnancies in women over 40 years remain unplanned: review of 2006 data from the US puts this figure at 48% .
Current use of contraception
Contraceptive use varies significantly between developed and developing countries, and is often related to health economics and long-established traditions. Significant trends in contraceptive use are related to age in most countries ( Table 1 ); the biggest variable for older women globally is usually prevalence of male and female sterilisation procedures ( Table 2 ).
| Method | 40–44 years UK | 45–49 years UK | 40–44 years USA |
|---|---|---|---|
| None | 25 | 28 | 31 |
| Pill | 10 | 13 | 8 |
| Male condom | 21 | 11 | 8 |
| Withdrawal | 6 | 4 | 1 |
| Intrauterine system | 3 | 4 | <1 |
| Intrauterine device | 9 | 11 | <1 |
| Injection | 2 | 4 | 1 |
| Implant | 0 | 1 | <1 |
| Patch | 1 | – | <1 |
| Natural method | 4 | 5 | 2 |
| Other | 0 | 1 | 1 |
| Female sterilisation | 18 | 19 | 35 |
| Vasectomy | 28 | 30 | 13 |
| Country | Female sterilisation (%) | Male sterilisation (%) |
|---|---|---|
| Japan | 43 | 1 |
| Brazil | 40 | 3 |
| China | 33 | 7 |
| UK | 18 | 17 |
| France | 7 | 0 |
| India | 5 | 1 |
| Zimbabwe | 1 | <1 |
Contraceptive choice
The availability of an acceptable, effective and convenient method of contraception is as important for perimenopausal women as for younger women. The method must be safe, and may be chosen to make the most of additional, non-contraceptive benefits. Each woman must have an individual assessment to determine suitability of the various options, and the benefits must be weighed against the risks.
Effectiveness and convenience of contraception
Significant numbers of unplanned conceptions occur in the months during which contraception has been used . Long-acting reversible contraceptive (LARC) methods that are more effective and user-independent lead to failure as a result of poor compliance. In countries in which sterilisation rates are declining, or have traditionally been low, many older women seek LARC methods for long-term contraception.
Safety of contraception
The World Health Organization has produced comprehensive guidance on medical eligibility for contraceptive use (WHOMEC) to aid safe prescribing. This has been adapted for use in individual countries . With increasing age, the background risk of adverse medical health issues increases, so that additional risks are associated with some methods. Of particular relevance in the perimenopause are the effects of contraception on cardiovascular risk, breast cancer, and loss of bone mineral density. To reflect this, WHOMEC recommends that women over the age of 50 years should stop combined hormonal contraception and injectable progestogen only contraception, and switch to a safer alternative method. Other than this, no contraceptive method is contraindicated by age alone.
Combined hormonal contraception
Combined hormonal contraception (CHC) is available as a daily pill, weekly transdermal patch (Evra/OrthoEvra © ), and monthly vaginal ring (Nuvaring © ). Almost all of these options contain between 15 and 35 mcg of the synthetic oestrogen ethinylestradiol in combination with a progestogen. The overall mean serum oestrogen ethinylestradiol concentrations with the patch are about 60% higher than with an oral preparation containing 35 mcg oestrogen ethinylestradiol (although the patch avoids the higher peaks associated with daily oral ingestion). The vaginal ring delivers a 15 mcg daily oestrogen ethinylestradiol dose and achieves steady plasma oestrogen ethinylestradiol concentrations that are lower than those for the pill . It is not known if using a lower oestrogen dose has any advantage for older women, and may indeed result in poorer cycle control .
In recent years, combined contraceptive pills have been developed that contain oestradiol esters rather than ethinylestradiol. It is postulated that, by using an oestrogen that is identical to naturally occurring human 17β ostradiol, these pills might offer a safer alternative to traditional combined contraceptive pills . Qlaira/Natazia © is a quadriphasic preparation containing oestradiol valerate combined with dienogest. Zoely © is a monophasic preparation containing oestradiol hemihydrate and nomegestrol acetate. Both have short hormone-free intervals, and offer good cycle control .
Indications and contraindications are currently broadly similar for all combined pills, patch and ring, and all provide contraception of comparable efficacy . Current guidance states that, provided the standard contraindications do not apply, perimenopausal women can use CHC until the age of 50 years .
Health benefits of combined hormonal contraception in the perimenopause
For perimenopausal women under the age of 50 years, combined hormonal contraception offers effective (although user-dependent) contraception with the additional potential advantages of good cycle control, treatment of vasomotor symptoms, protection against bone loss, and reduced risk of several cancers.
Cycle control and management of heavy menstrual bleeding
For most women, CHC results in regular, predictable bleeding that is lighter than their usual menstrual loss. Small trials have demonstrated a significant reduction from baseline heavy menstrual bleeding (HMB) with low-dose combined oral contraceptives, although the effect seems less than that with the intrauterine system, and roughly similar to that achieved with mefenamic acid . The effect of CHC on cycle control may be particularly beneficial to women with menstruation that is heavy, erratic, or both, in the perimenopause (once investigation has excluded underlying pathology) .
Across all combined oral contraceptive (COC) users, irregular bleeding seems to be more likely with 20 mcg oestrogen ethinylestradiol combined pills than with those containing 30 or 35 mcg . Recent studies show oestradiol-containing COC to be effective in managing HMB . The vaginal ring seems to be associated with less breakthrough bleeding than COC .
Menopausal symptoms
Vasomotor symptoms experienced during the perimenopause can be effectively managed by CHC. Women who are younger at the time of approaching menopause may find use of CHC a more acceptable option than conventional hormone replacement (HRT). Where flushes and sweats recur in the COC hormone-free interval, continuous or extended regimens with shorter pill-free intervals are useful . Extended regimen use of combined patch and ring is not currently recommended.
Bone protection
Among perimenopausal women who have become hypo-oestrogenic, low-dose COC (20–35 mcg) protects against loss of bone mineral density. Studies suggest that, for these women, bone mineral density increases with the use of COC compared with control groups taking calcium only. Women treated with COC maintain bone mineral densities compared with those of age matched, normally menstruating women . Insufficient data are available to confirm whether this would result in a reduction in future post-menopausal osteoporotic fractures.
A Cochrane review looking at all women rather than just hypoestrogenic perimenopausal women found no difference in bone mineral density (BMD) between COC users and non-users, and inadequate studies investigating actual fracture risk
Ovarian and endometrial cancer
Users of COC have a significant reduction in relative risk of both ovarian cancer and endometrial cancer, which increases with duration of use and persists (but reduces) over the 20–30 years after cessation of use .
Analysis of data from epidemiological studies relating to large numbers of women with ovarian cancer suggests a 20% reduction in the risk of ovarian cancer for every 5 years of COC use. The risk reduction for endometrioid and serous cancers is greater than that for mucinous cancers . Subsequent data support a significant risk reduction that increases with duration of use .
Most data relate to COC containing over 35 mcg oestrogen ethinylestradiol, and it is not known if lower dose preparations exert a similar protective benefit .
Chemoprophylaxis with COC against ovarian cancer may be particularly pertinent to women with BRCA 1 or 2 gene mutation. These women have a reduction in ovarian cancer risk with COC use comparable to that described for all women: risk is reduced by ever use of COC, and falls more with longer duration of use. It has been suggested that, for BRCA gene carriers, COC might offer an alternative to ‘risk reduction’ oophorectomy . This benefit must be weighed against the potential increased risk of breast cancer with COC use, which rises sharply with increasing age . Use of CHC may be a good chemoprophylactic strategy in younger women, but requires more caution in older women at higher risk of breast cancer unless they have had bilateral prophylactic mastectomy.
Endometrial cancer incidence rises sharply after the age of 50 years. Ever users of COC had a relative risk of 0.58 in the data from the UK RCGP Oral Contraception cohort study . Across available data, a consistent risk reduction of about 50% with ever use of COC is seen: the risk reduction increases with duration of use. Again, it is not clear if lower dose COC formulations exert this potent protective effect, and what the influence of different progestogens might be .
Health risks with combined hormonal contraception in the perimenopause
Venous thromboembolism
Venous thromboembolism (VTE) is significantly increased by CHC, and represents the main significant risk across all ages. The incidence of VTE in all women of reproductive age is estimated at about 4–5 per 10,000 woman years compared with non-users, in whom the relative risk of VTE in women using COC seems to be about 3–3.5.
Risk of VTE increases significantly with age, irrespective of whether a woman uses CHC. Recent figures from large Danish cohort studies suggest VTE incidence among non-COC users aged between 45 and 49 years is 5.8 per 10,000 woman years: almost three times that for women aged 20–24 years. By comparison, COC users aged between 45 and 49 years had a VTE risk of 20.8 per 10,000 woman years .
Pills containing 30–35 mcg oestrogen ethinylestradiol combined with gestodene, desogestrel, drospirenone and cyproterone acetate seem to confer a higher VTE risk than those containing levonorgestrel . Risk of VTE may be lower at lower oestrogen ethinylestradiol dose . A COC containing 20 mcg ethinylestradiol in combination with a second-generation progestogen may be the safest combination from the VTE perspective. The effect of the new oestradiol-containing COCs on VTE is not yet established.
Women using the combined transdermal patch and vaginal ring may be at higher risk of VTE than users of COC. The Danish cohort study figures demonstrate rate ratios for VTE events of 2.3 (1–5.2) for the patch, and 1.9 (1.3 – 2.7) for the ring compared with 30 mcg oestrogen ethinylestradiol and LNG COC .
Risk of VTE is greater for women who are obese, immobile, or have a personal or family history of VTE, and CHC is generally contraindicated in these women . Perimenopausal women under the age of 50 years choosing between CHC and HRT for symptom relief and bone protection in the perimenopause should be aware that HRT (particularly transdermal HRT) confers a lower VTE risk than CHC .
Arterial disease
A woman using low-dose COC is much less likely to have an arterial thrombotic event than a venous thrombosis. The consequences of arterial thrombosis, however, are extremely serious. The risk of myocardial infarction and stroke rises steeply with age, making these particularly relevant to perimenopausal women in their late forties.
Because the event rate for arterial disease in women of reproductive age is low, any effect of CHC on incidence of myocardial infarction and stroke is difficult to study. UK figures suggest an annual incidence of ischaemic stroke of 2.4 per 10,000 for women aged 45–54 years , and an annual incidence of myodcardial infarction of 0.2 per 10,000 for women aged 30–54 years .
Danish cohort study data show a significantly greater incidence of thrombotic stroke and heart attack amongst COC users than non-users (RR about 1.5–2.2), varying with oestrogen ethinylestradiol dose and progestogen . A systematic review of all available trial evidence supports the finding of a twofold increase in risk of thrombotic stroke for current COC users. It concludes, however, that inadequate evidence is available to confirm significantly increased risk of myocardial infardction, and the relative safety of preparations containing different progestogens or different oestrogen ethinylestradiol doses is not proven . The combined vaginal ring, and particularly the transdermal patch may confer a higher likelihood of stroke than COC .
Where other independent risk factors for arterial disease exist, use of CHC is contraindicated. Current UK Medical Eligibilty Criteria guidelines advise against CHC use in smokers over the age of 35 years, in hypertensive women, in those with a history of ischaemic heart disease or stroke, where there is a history of migraine with aura, and in women with antiphospholipid antibodies .
Breast cancer
Breast cancer is relatively common in the western world: the UK incidence in women aged between 45 and 54 years is about 24 per 10,000, rising to about 40 per 10,000 for women in their late sixties . A small increase in relative risk could therefore represent a significant increase in breast cancer incidence in this age range. In women with a personal history of breast cancer CHC is contraindicated, although a family history does not contraindicate use (see earlier for BRCA carriers).
The most frequently quoted statistic for breast cancer risk with current or recent use of COC compared with non-recent use is a relative risk of 1.24 (95% CI 1.15 to 1.33) . Results of subsequent studies have been conflicting, with several studies showing no significant effect . Data specifically relevant to women in the perimenopause are lacking. One study, however, reported data for a subgroup of current older users, suggesting a non-significant relative risk with COC use compared with non-use of 1.3 (95% CI 0.7 to 2.1) .
Cervical cancer
Use of COC increases the risk of cervical cancer, with a relative risk that increases with duration of use and reduces with time after stopping. A large 2007 collaborative reanalysis of available data suggested a relative risk with over 5 years of current COC use of 1.9 (95% CI 1.69 to 2.13), the effect diminishing after discontinuation of use and non-significant after 10 years .
The precise mechanism for this increased risk with COC is unknown, although COC may act as a co-factor in the presence of human papilloma virus (HPV) infection. The effect of HPV vaccination programmes on cervical cancer risk in women using COC long term remains to be evaluated. For such older women with access to cervical screening programmes, the benefits of continuing COC for effective contraception and other health benefits generally outweigh any increased cervical cancer risks.
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