Key learning points:
– There are different causes of the menopause, such as premature ovarian insufficiency
– Gain awareness of the various symptoms and manifestations of the menopause
– Understand the true benefits and risks of hormone replacement therapy
The menopause is the last spontaneous menstrual period that a woman has and represents the end of reproductive life and the transition into the post-reproductive state. A gradual reduction in ovarian function starts in the thirties with declining oestrogen levels, but the fall in oestrogen levels becomes steeper around the time of menopause. This is known as the perimenopause, and oestrogen deficiency symptoms may arise before menstruation has ceased.
The normal decline in oestrogen levels in the luteal phase of the ovarian cycle becomes steeper, often triggering premenstrual symptoms such as mood swings and irritability. This is why premenstrual tension (PMT) gets worse as a woman ages and gets closer to the menopause. When insufficient oestrogen is produced to stimulate endometrial growth, menses will cease.
The average age of menopause is 51 years, but this can vary considerably. A small number of women will continue to menstruate until their late fifties, while others will undergo a spontaneous menopause much younger. Women undergoing a menopause before the age of 40 years are now termed to have premature ovarian failure.1 Although small in number, this is a very important group as these women will be at increased risk of premature cardiovascular disease and premature osteoporosis.
Causes of menopause
As well as spontaneous menopause, there are other causes. The removal of both ovaries in a premenopausal woman, for any reason, results in a surgical menopause. This causes a very abrupt drop in oestrogen levels, and oestrogen deficiency symptoms are often very pronounced. It should be remembered that the postmenopausal ovary continues to produce some androgens and thus surgical menopause will usually cause simultaneous testosterone deficiency as well as oestrogen deficiency. Other causes of iatrogenic ovarian failure include radiotherapy and chemotherapy, which may of course occur in younger women.
Symptoms, signs and consequences
Table 1 outlines the symptoms, signs and consequences of menopause (see page 47). The most common symptoms of menopause are vasomotor symptoms; hot flushes and night sweats. These can vary considerably in both frequency and intensity, and in some women can be completely debilitating.
Women who have night sweats occurring several times during the night and resulting in the necessity to get up and change their nightwear will become sleep-deprived, which in turn will affect mood and tiredness.
Menopausal psychological symptoms are also common, with mood swings, irritability, anxiety and depression, wich can adversely affect relationships with partners and family.
Cognitive function is affected by oestrogen deficiency2 and difficulties with memory and concentration often occur. Genito-urinary symptoms may arise, sometimes several years after menopause. Vaginal dryness can cause painful intercourse (dyspareunia) that may limit or even prevent sexual intercourse.
Loss of libido may also occur with oestrogen deficiency, but this may also be a symptom of testosterone deficiency. As well as vaginal atrophy, lack of oestrogen may result in atrophic changes in the urethra and bladder neck.3 Increased urinary frequency and urgency may thus result from oestrogen deficiency, and recurrent “sterile urinary tract infections” may present.
Palpitations and even cardiac dysrhythmias can also occur. Joint pains, particularly those in the small joints of the hands and feet may be a menopausal symptom.4
Long-term consequences of the menopause should also be considered. Loss of ovarian function results in bone loss, and this can lead to the development of postmenopausal osteoporosis and an increased risk of fractures.5 Cardiovascular disease, in particular coronary heart disease, increases following menopause. Oestrogen deficiency can have adverse effects on the heart and blood vessels.6
Angina due to myocardial ischaemia can first arise, or be worsened, following the onset of menopause. Angina may be caused by obstruction of the major coronary arteries by atheroma, but can otherwise be due to dysfunction of the small arteries and arterioles in cardiac muscle, a condition known as microvascular angina (formerly syndrome X angina). Oestrogen deficiency can contribute to the development of osteoarthritis and arthralgia, as mentioned previously.
Risks and benefits of hormone replacement therapy
The treatment of the menopause, particularly with respect to HRT, has been complicated. Recently, The National Institute for Health and Clinical Excellence (NICE) published guidelines for menopause management (see Resources section), which may help to clarify and reassure practitioners.
The report emphasises the benefits of hormonal treatment for menopausal symptoms. Diagnosis of menopause should be made on clinical grounds and NICE recommends avoidance of unnecessary biochemical tests. The guidance also clarifies the benefits and risks of HRT.
HRT, sometimes referred to as menopausal hormone therapy (MHT), is one of the mainstrays of menopause management. The therapy comprises oestrogen given on a continuous basis, together with progestogen addition for endometrial protection in women with a uterus. The progestogen is provided on a cyclical basis for 12-14 days per month for women who are perimenopausal or within a couple of years of the onset of menopause. Additionally, it is given on a continuous basis for women who are established in menopause to avoid cyclical bleeding (because of intermittent bursts of ovarian function, continuous combined HRT is often not suitable for women in their very early menopause because of erratic spotting and bleeding).
Women starting on continuous combined HRT should be informed that any initial spotting or bleeding should not be a concern as it will usually remit spontaneously within the first three months and certainly by six months.
Both oestrogen and progestogen may cause some breast tenderness, but with respect to oestrogen, women should be reassured that this will usually settle within the first three months of use, similar to the breast tenderness seen in early pregnancy. Progestogens are more likely to be responsible for adverse symptoms with HRT, such as pelvic pain, backache and mood swings.
Women starting on HRT should be assessed after three months to see if there are any symptoms suggestive of progestogen intolerance, and if so, the type of progestogen should be changed. Some women are unable to tolerate any progestogens given systemically, and in such cases progestogens given locally by the progestogen-releasing intra-uterine systems (mirena and jaydess) or by vaginal gel (crinone) may be an option.
A new concept of HRT – the tissue selective estrogen complex (TSEC)7 – replaces the progestogen in HRT with a selective estradiol receptor modulator (SERM). It may be an effective alternative for those with progestogen intolerance when it becomes available in the UK.
Women with an early menopause or with more severe symptoms may require a higher dose, while for older women who are a few years beyond menopause, low or very low starting doses are more appropriate. If necessary, doses can be titrated upwards until symptomatic relief is achieved. For women with genito-urinary symptoms, local vaginal oestrogen may be sufficient and very effective.
HRT is usually initiated within the first 10 years of menopause onset. Occasionally, there is a need to initiate HRT in older women, and here the dose is critical. An ultra-low dose should be used at initiation, although the dose can be titrated up as necessary. It is best done slowly, say at three-monthly intervals, in order to minimise any side effects or risks.
The safety of HRT has been greatly debated in recent years, largely due to misinterpretation of results from large randomised clinical trials such as the Women’s Health Initiative (WHI)8 or from flawed observational studies such as the Million Women Study (MWS).9
An increasing number of studies and meta-analyses have shown that HRT does not increase coronary risk and, when given appropriately (initiating with the correct dose, correct type of hormones, and at the correct age), the totality of current data shows that it is effective for prevention of coronary disease and events.10 There is a small increased risk of venous thrombo-embolism with oral HRT, which may well be dose-dependent and is not usually seen with non-oral administration.11 Any increased risk of stroke is probably also dose-dependent, may also be lessened with non-oral administration, and is negligible in women initiating HRT below the age of 60.8
The biggest, and most debated concern is the risk of breast cancer with HRT. Observational data has suggested a small increase in breast cancer associated with HRT use, although this may be confined to the combination of oestrogen plus progestogen and may then depend on the progestogen type.12
The WHI initially reported an increase in breast cancer diagnosis with combined HRT, although this was not statistically significant. In contrast, with oestrogen-alone HRT there was a non-significant decrease.
Further analyses of the full trial results showed a significant increase in breast cancer, but this became non-significant when adjusted for confounding variables.8 With follow-up of the studies, the decrease in breast cancer with oestrogen-alone HRT became statistically significant compared with placebo.13
The current situation can be summarised by stating that HRT may or may not cause an increase in risk of breast cancer diagnosis but no study has proved beyond doubt that it does. The risk of breast cancer with HRT should therefore be put into perspective when counselling women about HRT use.
Primary care nurses are well situated to be able to help women entering the menopause by providing them with the facts about what the menopause is, and for which symptoms it may be responsible.
Women with symptoms of oestrogen deficiency can be counselled and advised about their choice of management.
NICE menopause guidance–
1. Panay N, Fenton A. Premature ovarian failure: a growing concern. Climacteric 2008;11:1-3.
2. Maki PM, Sundermann E. Hormone therapy and cognitive function. Human Reproduction Update 2009;15:667-81.
3. Robinson D, Cardozo LD. The role of estrogens in female lower urinary tract dysfunction. Urology 2003;62 supplement 1:45-51.
4. Wluka AE, Cicuttini FM, Spector TD. Menopause, oestrogens and arthritis. Maturitas 2000;35:183-99.
5. Stevenson JC, Stevenson TEJ. Is it safe to prevent and treat osteoporosis? In: Genazzani AR, Brincat M, eds. Frontiers in gynecological endocrinology Volume 1. From symptoms to therapies. Heidelberg: Springer, 2014:207-14.
6. Stevenson JC, Gerval MO. The influence of sex steroids on affairs of the heart. In: Genazzani AR, Brincat M, eds. Frontiers in gynecological endocrinology Volume 1. From symptoms to therapies. Heidelberg: Springer, 2014: 225-31.
7. Pickar JH, Mirkin S. Tissue-selective agents: selective estrogen receptor modulators and the tissue-selective estrogen complex. Menopause International 2010;16:121-8.
8. Stevenson JC, Hodis HN, Pickar JH, Lobo RA. Coronary heart disease and menopause management: the swinging pendulum of HRT. Atherosclerosis 2009;207:336-40.
9. Shapiro S, Farmer RDT, Stevenson JC, Burger HG, Mueck AO. Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies. Part 4. The Million Women Study. Journal of Family Planning and Reproductive Health Care 2012;38:102-09.
10. Salpeter SR, Walsh JME, Greyber E, Salpeter EE. Coronary heart disease events associated with hormone therapy in younger and older women. Journal of General Internal Medicine 2006;21:363-6.
11. Canonico M, Fournier A, Carcaillon L, et al. Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism. Results from the E3N cohort study. Arteriosclerosis Thrombosis, and Vascular Biology 2010;30:340-345.
12. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Research and Treatment 2008;107:103–11.
13. Manson JE , Chlebowski RT, Stefanick ML , et al. Menopausal hormone therapy and health outcomes during the interventions and postintervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 2013;310:1353-68.
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