Beyond their primary role of preventing pregnancy, hormonal contraceptives provide a number of non-contraceptive benefits (Table 1), the most well-established of which are described in this article. Some of these benefits may be key factors affecting a woman's contraceptive choice, such as effect on menstrual bleeding; while others may be more secondary advantages, such as reduction in the lifetime risk of certain cancers.
Table 1. Summary of non-contraceptive benefits of hormonal contraception
| Menstrual disorders |
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| Gynaecological conditions |
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| Malignancy |
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| Others |
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Hormonal contraceptives also have an important role in the management of many gynaecological conditions, some of which may be outside standard product licenses, but are supported by clinical guidelines.Where a drug is used outside its product license, the prescriber should discuss the proposed treatment fully with the patient and be satisfied that there is sufficient clinical evidence to support its use. In the case of contraception, the Faculty of Sexual and Reproductive Healthcare (FSRH) produce evidence-based guidance on contraceptive prescribing in the UK, including clear indications for off-label use. The UK Medical Eligibility Criteria (UKMEC) summarises the suitability of each method for contraceptive purposes only. Although the risks may outweigh the benefits when a method is used solely for contraception, the risk-benefit profile may change when it is used for a medical indication, and expert clinical judgment should always be sought.
Menstrual disorders
Heavy menstrual bleeding
Most hormonal contraceptives will alter menstrual bleeding. For those with heavy, painful or irregular periods this may be an attractive side-effect; but for any woman it is often an important consideration in method selection. Hormonal treatment options recommended in National Institute for Health and Care Excellence (NICE) guidance for the management of heavy menstrual bleeding include the 52 mg levonorgestrel intrauterine system (LNG-IUS) and combined hormonal contraception (NICE, 2018a). Although both have been shown to reduce heavy menstrual bleeding, LNG-IUS demonstrated a greater and more sustained treatment effect (Shabaan et al, 2011). As such, the LNG-IUS is recommended as first-line therapy by NICE in the absence of large fibroids or other pathology (NICE, 2018a) (Table 2). The reduction in hysterectomy procedures performed for menstrual indications in recent decades can be partly attributed to the increased use of the LNG-IUS. However, women should be advised that it may take up to 6 months for an improvement to be seen.
Table 2. First-line use of LNG-IUS in heavy menstrual bleeding
| Criteria for first-line use of the LNG-IUS in the management of women with heavy menstrual bleeding: |
|---|
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From: National Institute for Health and Care Excellence (2017)
LNG-IUS, levonorgestrel-releasing intrauterine system
Combined hormonal contraception is frequently used as a treatment for heavy menstrual bleeding. Both cyclical 21/7 (standard) and continuous or extended (tailored) regimens lead to a reduction in menstrual bleeding; however, amenorrhoea is more common with continuous administration. FSRH (2019a) guidance supports the use of tailored combined hormonal contraception regimens for contraceptive and non-contraceptive indications, and this option should be offered to all women using these methods. Women can also be advised that breakthrough bleeding is no more likely to occur using this approach, and may in fact improve (Edelman et al, 2014). The combined vaginal ring has also been shown to reduce menstrual bleeding to a similar extent as combined oral contraceptives and may result in less breakthrough bleeding and better adherence (FSRH, 2019a).
The role of progestogen-only contraceptives (injectables (DMPA), subdermal implant or progestogen-only pill) in the management of heavy menstrual bleeding is also recognised in the NICE guidance, due to their potential to cause amenorrhoea in some women. Particularly high rates of amenorrhoea are seen in DMPA users, with at least 50% of women expected to have absent periods at 12 months, increasing further over time (Hubacher et al, 2009). However, women should also be aware that with any progestogen-only method, amenorrhoea is not guaranteed, and irregular bleeding is common, particularly in the first few months of use.
Dysmenorrhoea
Dysmenorrhoea, also known as painful periods, may be primary (in the absence of other pathology) or secondary to another underlying condition. Primary dysmenorrhoea often presents in adolescence and combined hormonal contraceptives are frequently used as a first-line treatment option. Continuous combined hormonal contraception has been shown to be superior to cyclical use in the management of primary dysmenorrhoea (Dmitrovic et al, 2012). Edelman et al (2014) showed that unpredictable bleeding was no more likely to occur with continuous administration.
The most common cause of secondary dysmenorrhoea is endometriosis, which affects 1 in 10 women of reproductive age in the UK (NICE, 2017). It occurs due to the presence of endometrial tissue outside the inner uterine lining, most frequently the pelvis and associated organs such as the ovaries and fallopian tubes. Where endometrial tissue invades the deeper muscular layer of the uterus, the myometrium, it is known as adenomyosis.
The most widely accepted pathological basis of endometriosis is one of retrograde menstruation, with the subsequent ectopic endometrial tissue responding to cyclical hormone stimulation in the same way as normal endometrium. However, in the absence of natural endometrial ‘shedding’ during menstruation, ectopic endometrial stimulation causes inflammation and pain, which for some women can lead to scar tissue formation, cyst development and secondary infertility.
Management of endometriosis is often complex and can involve lifestyle, pharmacological and surgical intervention. For women who do not wish to conceive, hormonal methods of contraception (eg combined hormonal contraception, DMPA, intrauterine system) can be used by those with suspected or confirmed endometriosis either before or as an adjunct to surgical intervention (NICE, 2017). The theoretical basis for hormonal methods is to abolish cyclical menstrual activity in an attempt to regress inflammation and prevent disease progression. However, hormonal treatment has not been shown to improve subsequent spontaneous pregnancy rates, and therefore surgical management is preferred for women with endometriosis wishing to conceive. Combined hormonal contraception has also been shown to reduce the risk of recurrence following surgical disease excision (Wu et al, 2013). When used post-operatively, continuous combined hormonal contraception use has been shown to be superior to cyclical use in delaying disease recurrence (Muzii et al, 2016).
Endometriosis is a common cause of infertility, particularly in those with severe disease. While hormonal treatments can lead to a reduction in pain and improve quality of life, they have not been definitively shown to increase spontaneous conception in women with endometriosis (Hughes et al, 2007). However, women can be reassured that hormonal treatments do not have any long-term negative effect on fertility (with the exception of DMPA, which can delay the return to baseline fertility for up to 1 year after stopping).
Premenstrual syndrome
Many women experience premenstrual symptoms such as breast tenderness, bloating, mood changes and fatigue. However, up to one third of women of reproductive age experience premenstrual syndrome (PMS) where the psychological or physical symptoms are severe enough to interfere with their daily activities and quality of life (Biggs and Demuth, 2011). By definition, these symptoms arise in the week or two before menstruation (luteal phase) and resolve or improve with the onset of menstrual bleeding. As such, a menstrual diary is often helpful in the diagnosis of the condition (Royal College of Obstetricians and Gynaecologists (RCOG), 2017). If symptoms are particularly severe and involve mood disturbance, the rare diagnosis of premenstrual dysphoric disorder (PMDD) may be made (Biggs and Demuth, 2011).
The aetiology of PMS is uncertain, although the absence of the condition during pregnancy and after menopause indicates that the ovarian hormone cycle is central to its origin. The use of hormonal contraceptives in the treatment of PMS and PMDD is based on the theory that suppressing ovulation and abolishing the natural hormone cycle will reduce premenstrual symptoms. However, the wide variation in clinical presentation of the condition and the potential for hormonal treatments to induce PMS-like side effects, make clinical trials of combined hormonal contraception difficult to interpret. More recent research has focused on combined oral contraception containing newer progestogens, with the potential to minimise treatment side effects.
Drospirenone is a non-androgenic progestogen with anti-mineralocorticoid (spironolactone-like) properties, which has been studied widely in PMS. A systematic review published in 2012 included five trials of drospirenone in the treatment of PMS symptoms (Lopez et al, 2012). A significant symptom reduction was noted in those with severe baseline symptoms (consistent with PMDD); however, its role in women with less severe symptoms, or in comparison to other combined oral contraceptives, remains unclear. Based on the available evidence, RCOG recommends the use of drospirenone-containing combined oral contraceptives in the management of PMS symptoms, either on a continuous or cyclical basis (RCOG, 2017) but it may not offer significant advantages over other combined oral contraceptives in those with less severe symptoms. When using combined oral contraceptives to treat women with PMS, more recent data suggest that continuous therapy is associated with greater symptom improvement and more long-term adherence to therapy (RCOG, 2017).
There is no evidence that treating PMS with progestogens alone (including LNG-IUS) is of any benefit (Ford et al, 2012). However, LNG-IUS 52 mg can be used to provide endometrial protection alongside systemic estradiol for ovulatory suppression. This can minimise the systemic side effects of other cyclical progestogens; however, women using this regimen should be advised about the potential for PMS-type symptoms and bleeding problems in the early months of use.
Perimenopause
Perimenopausal women often experience irregular and/or heavy menstrual bleeding due to the increasing number of anovulatory cycles experienced in the years leading up to the menopause. As ovarian oestrogen production diminishes, women may also experience vasomotor symptoms such as hot flushes and night sweats.
‘Perimenopausal women often experience irregular and/or heavy menstrual bleeding due to the increasing number of anovulatory cycles experienced in the years leading up to the menopause.’
As discussed, LNG-IUS 52 mg is a therapeutic option for heavy menstrual bleeding and can therefore be of benefit to women experiencing problematic bleeding in perimenopause. However, for women over 40 years old who are experiencing a sudden, significant change in bleeding pattern, an underlying pathology should be considered and excluded (FSRH, 2017). The FSRH support the extended use of LNG-IUS 52 mg, which can be used for as long as it is controlling symptoms, regardless of the age at time of insertion, when only being used for HMB (FSRH, 2017). When using it for contraception, women who are aged 45 years or older at the time of fitting can retain their Mirena IUS until age 55 years (FSRH, 2017).
Combined hormonal contraception appears to be of benefit to women experiencing vasomotor symptoms, with studies showing a reduction in symptoms, particularly in women using extended or continuous regimens (FSRH, 2019a). In addition, the predictable bleeding pattern of combined hormonal contraception can be beneficial to women experiencing troublesome bleeding associated with perimenopause.
Combined hormonal contraception has been found to have a positive effect on bone mineral density, which is particularly relevant for women in perimenopause. A Cochrane review of 19 randomised controlled trials found that combined hormonal contraception can increase bone mineral density, although the studies were of low quality (Lopez et al, 2014). A series of prospective cohort studies reported that combined hormonal contraception users had either no change or an increase in bone mineral density, whereas the control groups had reduced bone mineral density (Gambacciani et al, 2000). In suitable women under the age of 50 years, combined hormonal contraception can be used as both contraception and as an alternative to hormone replacement therapy. However, increasing age is associated with an increased risk of comorbidities, which could contraindicate the use of combined hormonal contraception or exacerbate the risk of associated adverse events.The risks and benefits of combined hormonal contraception use for a woman in perimenopause need to be carefully reviewed on an individual basis. The FSRH recommends that at age 50, the risks of combined hormonal contraception outweigh the benefits and women should switch to a safer alternative.
An analysis of epidemiological studies concluded that ever-use of an intra-uterine device may have a protective effect against cervical cancer
Hyperandrogenism
Hyperandrogenism is a common endocrinopathy that can cause symptoms such as acne, hirsutism and irregular menses. The most common cause of clinical hyperandrogenism in women of reproductive age is polycystic ovary syndrome (PCOS), although there are many other underlying pathologies that can cause raised levels of circulating testosterone. Combined hormonal contraceptives can be beneficial in treating the symptoms of hyperandrogenism.
The pathophysiology of hyperandrogenism is often multifactorial, but can be a result of decreased serum sex hormone binding globulin (SHBG) production by the liver and increased androgen production. SHBG binds to testosterone resulting in lower levels of circulating free testosterone. Conversely, with decreased SHBG production (as seen in PCOS), levels of unbound, active testosterone rise resulting in hyperandrogenism. Combined hormonal contraceptives stimulate the production of SHBG, lowering levels of free androgens. Combined hormonal contraceptives also have a beneficial effect on luteinising hormone, which is often elevated in hyperandrogenism. Luteinising hormone acts on ovarian theca cells to convert cholesterol to androgens and these androgens are then converted by follicle stimulating hormone to estradiol. Elevated luteinising hormone levels without a concurrent rise in follicle stimulating hormone levels, result in increased androgen production and hyperandrogenism. Combined hormonal contraceptives inhibit pituitary secretion of luteinising hormone, preventing increased androgen production.
There is good evidence that combined oral contraceptives are an effective treatment for acne vulgaris and they are one of many treatment options available (NICE, 2018b). A number of trials have shown that compared to placebo, combined oral contraceptives reduce the number of acne lesions and the severity grades of acne (FSRH, 2019a). For the reasons described above, any combined oral contraceptive preparation is likely to be beneficial for women with acne, and there is currently insufficient evidence to show that one preparation is superior to another. There are fewer studies looking at use of combined vaginal ring/combined transdermal patch, but the available evidence suggests that these can also be beneficial for women with acne (FSRH, 2019a).
There have been only been a small number of studies examining the effect of combined oral contraceptives on hirsutism, and the evidence available is of low quality (FSRH, 2019a). Nonetheless, the beneficial effects of lowering serum androgens is expected to be the same as for acne, and combined oral contraceptives are recommended as a first-line treatment for hirsutism (FSRH, 2019a). The Endocrine Society also recommends combined hormonal contraceptives as a first-line treatment for PCOS in women who are not trying to conceive, due to its beneficial effects on acne, hirsutism and menstrual irregularity (Legro et al, 2013). The protective effect of combined hormonal contraceptives against endometrial hyperplasia and carcinoma is an additional benefit for women with PCOS whose oligo- or amenorrhoea predisposes them to an increased risk of these conditions.
Malignancy
There is extensive evidence from epidemiological studies that combined oral contraceptives offer a reduction in the risk of ovarian, endometrial and colorectal cancers. Additionally, intrauterine and injectable contraception may also offer some protection against malignancy.
Ovarian cancer
There is strong evidence that use of combined oral contraceptives significantly reduces a woman's risk of developing ovarian cancer. The protective effect is duration dependent, and is seen in women with and without a genetic predisposition to ovarian cancer and can last for 30 years after use (Bassuk and Manson, 2015). A large, meta-analysis of 45 studies concluded that for women using combined oral contraceptives, the relative risk of developing ovarian cancer reduced by 20% for every 5 years of use (Beral et al, 2008). Other studies have similarly shown that 10 years of combined oral contraceptive use is associated with a 40–50% reduction in risk of ovarian cancer when users are compared with non-users (Havrilesky et al, 2013; Michels et al, 2018). There is limited data from observational studies that Depo-Provera and LNG-IUS may also provide some protection against ovarian cancer (FSRH, 2015; 2019b).
Endometrial cancer
There is also a large body of evidence that shows that combined oral contraceptive use is associated with a reduced risk of endometrial cancer, which is duration dependent and can last for several years after cessation. Systematic reviews and meta-analyses have found up to a 50% reduction in risk with 10–15 years of use, and a persistent protective effect, lasting for up to 30 years after cessation (Collaborative Group on Epidemiological Studies on Endometrial Cancer, 2015). A large prospective cohort study that has since been published has demonstrated a 34% reduction in endometrial cancer with combined oral contraceptive use, with the greatest risk reduction observed in obese women and women who smoke (Michels et al, 2018).
The LNG-IUS 52 mg prevents endometrial proliferation and is used to prevent and treat endometrial hyperplasia. It has been shown to be effective in the treatment of early-grade endometrial cancer in those at high-risk of peri-operative complications (Montz et al, 2002). There is limited evidence from small, observational studies that DMPA may offer some protection against endometrial cancer (FSRH, 2015).
Other cancers
Despite a recent, large, prospective cohort study finding no significant association with combined oral contraceptive use and colorectal cancer (Michels et al, 2018), three previous meta-analyses of observational studies have concluded that combined oral contraceptive users have an 18–19% reduced risk of colorectal cancer when compared with never users (FSRH, 2019a).
An analysis of epidemiological studies concluded that ever-use of an intra-uterine device may have a protective effect against cervical cancer, with reduced rates of squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma of the cervix reported in women who were not also HPV-positive (FSRH, 2015).
Benign reproductive conditions
Functional ovarian cysts and benign breast disease, such as fibroadenomas, are common in women of reproductive age. Two large cohort studies have shown combined oral contraceptive use has a protective effect against benign breast disease (Brinton et al, 1981; Vessey and Yeates, 2007). Early studies established that combined oral contraceptives also showed a protective effect against functional ovarian cysts; however, a Cochrane review of seven randomised controlled trials concluded that combined oral contraceptives are not a beneficial treatment in the management of functional ovarian cysts that are already present (Grimes et al, 2014).
Conclusions
Hormonal contraception in its many forms can provide reliable prevention of unintended pregnancy, as well as a broad range of non-contraceptive benefits. For some women, these may form the primary indication for recommending one particular method over another, such as in the treatment of menstrual disorders or acne. However, a balanced and evidence-based discussion of non-contraceptive benefits should form part of any contraceptive choice consultation. It is therefore important for contraceptive providers to maintain their knowledge as evidence continues to emerge in this area.
KEY POINTS
- Many methods of contraception can also be used to manage menstrual disorders, including irregular bleeding, dysmenorrhoea, heavy menstrual bleeding and premenstrual syndrome
- Combined hormonal contraception can be used to manage symptoms of hyperandrogenism, such as acne, hirsutism and oligo-amenorrhoea
- Contraception can provide protection against malignancy, with a large body of evidence showing that combined hormonal contraception reduces the risk of ovarian and endometrial cancers, for decades after cessation
- Combined hormonal contraception can be beneficial for women in perimenopause
CPD reflective practice
- Consider your contraception choices consultation. What information do you give women about the non-contraceptive benefits of contraception? Having read the article, are there any gaps in the information that you provide and how will you address these?
- What specific questions do you need to ask women in order to ensure you can advise them on the methods of contraception that may provide the most benefit to them?
- Consider a woman who wishes to discuss contraception, but also reports having heavy periods. How would you approach the consultation and which methods might be most appropriate for her?