The Melbourne Women’s Midlife Health Project is a prospective, longitudinal study of healthy women passing through the menopause transition.³ The study began in 1991 and used random telephone dialling to recruit Australian-born women aged 45 to 55 years. One hundred and seventy-two women were premenopausal at the time at baseline, and by the end of the seventh year of annual follow-up had advanced to the peri- or postmenopausal interval.

By the postmenopausal period, almost all had recorded at least one symptom—the most common being hot flushes. As women transited from the premenopausal to the postmenopausal phase, they noted significantly less breast pain, but significantly more hot flushes, night sweats and vaginal dryness.

CULTURAL DIFFERENCES

There appear to be marked cultural differences in attitudes to menopause. In a study of Sydney women, Asian women generally appeared to view menopause in a more favourable light than Western women, who linked menopause with ‘getting older’. Asian women were also less likely to admit to a healthcare professional that they were suffering from vaginal dryness, but if a doctor raised the issue, they were very grateful.⁴,⁵

Among Indian women, only 34% complained of hot flushes; more were concerned about depression and memory loss.⁶ Unemployment was associated with more flushing and depression. Lebanese Muslim women reported high rates of feeling tired and worn out, as well as aches and pains, as they went through the menopause transition.⁷ Sixty-three per cent reported hot flushes and more than half had noticed vaginal dryness during intercourse.

Chinese women largely see menopause as a natural process.⁸ A group of Sydney-based Chinese women had more vasomotor symptoms (34%) than those women who live in mainland China (10.5%) or in Hong Kong (10–20%). The top three symptoms reported by Sydney-based Chinese women were poor memory (76.4%), dry skin (69.1%) and aching in muscles and joints (68.3%). Some told the interviewers that their vaginal dryness problem was so severe that they had given their husbands permission to have sex with someone else.

Among Greek women, most were more concerned about back pain, aches, pains and fatigue than about hot flushes.⁹ Seventy-nine per cent of the postmenopausal Greek women had vaginal dryness, and there was a high rate of sexual problems.

THE MENOPAUSE CONSULTATION

HISTORY

The initial menopause consultation is a long session and often takes at least 30 minutes. It might be facilitated by some pre-reading and by using one of the many menopause-scoring charts that are available, such as the MENQOL (Menopause-specific Quality of Life Questionnaire, Table 53.1).¹⁰

TABLE 53.1 Oestrogen deficiency symptom score, using MENQOL ¹¹

The following should be particularly considered while taking a ‘menopause’ history:

• The menstrual cycle. During the last 5 years of menstrual life, the cycle often shortens from 28 to even 21 days. Skipping months usually occurs during the last few years of menstruation. Variability is the norm. Some periods might be heavy with clotting, and others light. Bleeding lasting longer than seven days or continual bleeding needs to be investigated. Usually this means a transvaginal ultrasound scan and a referral for hysteroscopy and endometrial biopsy. Endometrial hyperplasia and cancer are increasingly common after the age of 40 years.

• Menopause symptoms (see Table 53.1)

• Contraception. Is the patient worried that she might ‘accidentally’ become pregnant? Has she used the oral contraceptive pill (OCP) in the past? If so, did she have any side effects? For example, if she became depressed on the Pill, this is a progestin side effect. Women who had ‘PMT-type’ side effects with levonorgestrel-containing OCP are usually also intolerant of other progestins such as norethisterone, cyproterone and medroxyprogesterone acetate (MPA), but may tolerate dydrogesterone.

• Sleep patterns. Sleep lightens with ageing, but at this time of life, sweats and flushes at night will often disturb sleep.

• Bladder and vaginal symptoms. Incontinence is common and, after menopause, vaginal dryness increases in prevalence; and apart from making vaginal intercourse uncomfortable and even painful, urinary tract infections increase in frequency.

• Mood. Severe depression and anxiety are not more common during the menopause transition, but those women with a pre-existing history of mood disorder commonly find that it worsens.

• Skin sensations. About one-third of perimenopausal women notice a peculiar skin sensation (no rash) called ‘formication’ or ‘ants under the skin’. Some describe it as like insects moving over the skin. It can be very unpleasant. The cause is not completely understood, but it does seem to be due to an effect of swinging hormone levels on nerve endings and usually passes after some months.

EXAMINATION

A woman may present to her doctor with a concern about menopause because of symptoms that she feels may be hormonally based. It is essential to have the diagnostic radar well-tuned for other possible explanations for symptoms. It is worth taking the opportunity to do a general physical examination and identify any possible risk factors for middle age and beyond. At the very least, it is prudent to check the woman’s blood pressure and weight, ensure that her Pap smears are up to date, and examine the breasts for abnormal lumps.

TESTS

A woman aged in her forties with amenorrhoea or slight periods should be tested for pregnancy. If a woman has ‘hot flushes’ and her blood pressure is elevated, a 24-hour ambulatory blood pressure monitor will reveal whether the flushes are symptomatic of hypertension.

All that flushes is not menopause. Consider the differential diagnosis of ‘night sweats’ (see below) including viral infection, tuberculosis, neoplasm, hyperthyroidism, sleep apnoea, gastro-oesophageal reflux disease, alcohol excess and hypoglycaemia.¹²

There is no place for the routine measurement of hormone levels (e.g. FSH and oestradiol (E2)). During the normal menstrual cycle, E2 levels fluctuate from very low (below 100 pmol/L) to 500–1000 pmol/L at ovulation. FSH levels more than 20 U/L suggest that the patient is perimenopausal. The problem is that perimenopausal women can have even more variation than usual. It is not unusual for E2 levels to be greater than 2000 pmol/L and FSH levels can vary from less than 10 U/L to more than 40 U/L. The typical patient who is over 40 years of age with irregular periods and typical symptoms does not need her FSH and E2 measured.

If early menopause is suspected in a woman under 30 years of age, it might be prudent to measure her FSH levels three times over 2–3 months. In this way, the diagnosis is usually readily confirmed. Antimüllerian hormone (AMH) is a relatively new blood test that may give some information on ovarian reserve.

Use this opportunity to check the results of her last Pap smear, mammogram, bone density, lipids and blood glucose measurement, and ensure that a regular testing protocol is established for the perimenopause and postmenopausal phase.

MANAGING MENOPAUSE

There are a number of important issues for a woman and her doctor to be mindful of in managing the menopause but there are also a wide range of options available to a woman in managing those issues. The management objectives include ameliorating symptoms associated with menopause as well as making efforts to minimise the risk of other illnesses that become more common after menopause, such as heart disease, cancer and osteoporosis. The management approaches outlined below focus on lifestyle issues and specific medical and complementary therapies.

LIFESTYLE ISSUES: THE ESSENCE MODEL

MANAGING HOT FLUSHES

In Western culture, the most common menopause symptom is the hot flush (referred to as ‘hot flash’ in American literature). This typically begins as a feeling of intense heat in the chest and neck which soon rushes up over the head and then over the rest of the body. It lasts a few minutes and might be associated with feelings of nausea, palpitations, dizziness and formication. The sufferer usually goes bright red and ends up with a drenching sweat, often followed by chills and shivering. The menopausal hot flush can be extremely unpleasant. The frequency varies considerably, from 1–2 a day to 10–20 an hour, day and night. During the flush, central temperature does not rise, but skin temperature goes up by 5–7°C.

Most women will have mild flushes for a couple of years, and then the temperature centre adapts and the flushes settle. In a significant minority (10–20%), flushes continue forever.

DIFFERENTIAL DIAGNOSIS

Not all flushing is due to menopause, and so it is important to ask the patient to describe her hot sensation. The differential diagnosis includes:

• fever—if the patient takes her central (mouth) temperature during a flush, it will be less than 37°C. If her temperature is more than 37.5°C, she has a fever and that will need to be investigated

• hyperhydrosis—these patients sweat all the time. It often especially affects the upper body and can be confused with hot flushes

• hypertension

• anxiety

• acne rosacea—causes facial flushing and can coexist with menopausal flushing

• hyperthyroidism—causes an increase in sweating, not flushes as such

• phaeochromocytoma—most of these secrete noradrenaline and so the sufferer will go pale and white because of vasoconstriction. During an attack they will be hypertensive and feel dreadful (‘like they are going to die’)

• carcinoid tumours—these secrete serotonin and the usual primary site is the bowel. During an attack, the patient may turn red, but they often have diarrhoea too and the attack usually lasts longer than a few minutes. If the patient had a colonic carcinoid tumour and has serotonin-symptoms, this usually indicates the presence of liver metastases

• some drugs—high doses of SSRIs, SNRIs and vasodilators can cause sweating and flushing

• very rare causes—mast-cell tumours secrete histamine (producing urticaria) and some rare parathyroid tumours secreting calcitonin can also elicit flushes.

The menopause flush is caused by disruption of the thermoregulatory system in the anterior hypohalamus.¹⁵ Basically, there are two ‘thermostats’: if core temperature goes above the high one, flushes occur; and if core temperature goes below the lower thermostat, shivering happens. For those with severe vasomotor symptoms, the two thermostats are close together, and thus sweating and shivering are more easily triggered in these women. Neurotransmitters such as serotonin and noradrenaline are involved, which, as we shall see shortly, has implications for therapy.

LIFESTYLE MODIFICATIONS

Avoidance of triggers can be helpful for some. Such triggers include stress, hot drinks, spicy foods, alcohol, over-heating and hot weather. There is some evidence that a diet high in soy and cereal can help those with mild flushes.¹⁶ Vigorous exercise can make flushes worse by overheating the body.

HERBAL

Most of the over-the-counter herbal therapies either have been shown not to be more effective than placebo or have not been formally tested.¹⁷ Sage (Salvia officinalis), dong quai (Angelica sinensis), red clover (Trifolium pratense), Asian ginseng (Panax ginseng) and kudzu (Pueraria lobata) are commonly recommended, but evidence for their effectiveness is lacking.

Nelson and colleagues performed a meta-analysis of non-hormonal therapies for menopausal hot flushes.¹⁸ They found that red clover extracts were no more effective than placebo but that there was some evidence that some soy extracts are effective (e.g. Phyto Soya®).

By far the most effective and tested herbal is a standardised extract of black cohosh. It has been submitted to several randomised controlled trials (RCTs). Osmers and colleagues performed a RCT of 304 women randomised to two tablets a day versus placebo.¹⁹ The active treatment was statistically significant for a global menopause score and specifically for vasomotor, mood and vaginal symptoms, despite the fact that the extract is not oestrogenic.

Uebelhack and colleagues performed a RCT of black cohosh and St John’s wort extract among 301 women.²⁰ Again the active compound was found to be superior to placebo for vasomotor and mood symptoms. St John’s wort can be combined with black cohosh. Palacio and colleagues reviewed trials of black cohosh.²¹ Most placebo-controlled trials showed that black cohosh was superior to placebo and equivalent to low-dose HRT and even tibolone. One trial even compared black cohosh with fluoxetine 40 mg and found that black cohosh was better for flushes and fluoxetine superior for moods.

Trials with black cohosh extracts have largely found no greater risk of side effects than placebo. However, there have been case reports of hepatic failure, probably autoimmune and idiosyncratic, associated with black cohosh. The incidence appears to be less than 1 in 100,000 cases.

Vitex agnus castus (chasteberry) 20 mg daily may help perimenopausal symptoms such as irregular menses and mastalgia.

OTHER COMPLEMENTARY AND ALTERNATIVE THERAPIES

Nedrow and colleagues have systematically reviewed complementary and alternative medicines (CAMs) used for menopausal symptoms.²² It can be challenging to design placebo for physical CAMs such as reflexology and acupuncture, but some researchers have managed to do so. One trial compared reflexology and ‘routine’ foot massage; and four trials used sham acupuncture needles. None of these treatments was found to be superior to sham treatment for the relief of menopausal symptoms. Nedrow and colleagues also reviewed six RCTs of Chinese herbal mixtures—all the RCTs were negative.

Slow, deep breathing—‘paced respiration’—can reduce the severity of a hot flush.¹⁵

NON-HORMONAL DRUGS FOR FLUSHES

An increasing number of ‘brain drugs’ are being used to treat menopausal symptoms. Intuitively this makes sense, because the vasomotor and mood symptoms are brain in origin. Currently, the most popular non-hormonal drugs (or, more correctly, ‘non-sex-hormonal’, as these drugs act primarily on brain ‘hormones’) for managing menopausal brain symptoms are listed below.

• SSRIs and SNRIs—Nelson and colleagues’ review examined seven RCTs and clearly showed evidence of efficacy.¹⁸ Typically the lowest tablet size was the most effective for treating hot flushes. High doses of these agents can actually cause hot flushes and sweats as a side effect. This is not unusual for hormonal agents. Many hormones in low pulsatile doses stimulate the target receptor, in contrast to high continuous doses, which often down-regulate the receptor. Typical doses used to treat flushes and mood swings of menopause include venlafaxine 75XR and citalopram 20 mg daily. The side effects of these agents are discussed elsewhere in this book.

• clonidine—most of the clonidine RCTs used doses of 0.05–0.15 mg daily.¹⁸ These doses were more effective than placebo. Side effects include hypotension, dry mouth, sedation and, in high doses, depression. Clonidine might be useful to manage both hypertension and flushes. It can also be used as a prophylactic migraine drug. It is not unusual for migraine frequency to increase at around the time of perimenopause, and to then settle after the last period.

• gabapentin—Toulis and colleagues ⁵ published a meta-analysis of studies trialling gabapentin (dose range 900–2400 mg) for treating hot flushes. This systematic review included seven trials. Gabapentin was found to be superior to placebo for reducing hot flushes. The main side effects can be headache, drowsiness, dizziness, nausea, disturbed sleep, fluid retention and weight gain. When the patient is coming off gabapentin, the dose should be reduced by 300 mg at a time every 3 days.

It is certainly helpful to have these agents available to the clinician and the patient. For example, consider a woman who has just completed chemotherapy for breast cancer and is now rendered menopausal. Her oncologist starts her on tamoxifen or an aromatase inhibitor and, not surprisingly, her flushes increase dramatically. Black cohosh, perhaps even combined with an SNRI, will help around 70–80%. These women are often grateful for a reduction in symptom severity, rather than complete resolution of their symptoms. It can be clinically useful to temporarily cease the endocrine therapy for 2–4 weeks to examine the impact of the drug on flushing severity.

A migrainous, hypertensive perimenopausal woman might choose to try clonidine. A patient suffering from trigeminal neuralgia and significant flushing might wish to try gabapentin, for both problems.

HORMONE THERAPY

Hormone therapy (HT), also known as hormone replacement therapy (HRT), remains controversial and should be reserved for women who are unable to tolerate symptoms of menopause and have not responded to other measures. The woman should be informed of the potential risks and side effects. If the decision is made to proceed with HT, the lowest effective dose should be prescribed, and reviewed regularly.

For the interested reader, Blake ² and Grady¹⁵ have recently reviewed the evidence base for managing menopause. HT has been around for a very long time—oestradiol implants since the mid-1930s and Premarin® (conjugated oestrogens) since 1942.

In Grady’s review, she demonstrates that 0.625 mg Premarin® and 1–2 mg E2 orally reduce hot flushes by around 90–95%, with a placebo effect of 45%.¹⁵ Relief is usually substantial within 4 weeks. Lower doses (e.g. 1 mg E2 daily) take longer to work but have a lower rate of side effects. Progestins are added to prevent endometrial hyperplasia. These are given either cyclically for 10–14 days or continuously, on a daily basis.

Using hormone therapy

The healthy perimenopausal woman seeking HT usually begins with a cyclical HT. Continuous HT does not suppress the cycle, and so breakthrough bleeding is common and can be troublesome. A short course of a low-dose OCP might be considered for a healthy, non-smoking, non-migrainous, normotensive woman under 50 years of age.

No matter what the regimen is, initial breast soreness and irregular vaginal bleeding are common, and usually settle with time. Around 10–15% will have progestin side effects—bloatedness, mood swings, even depression. Dydrogesterone is the best-tolerated oral progestin and, for some, the Mirena® intrauterine device might suit. If heavy menstrual periods need treatment, a Mirena® intrauterine device could be used to both control the menstrual problem and give endometrial protection, while giving a tablet or patch of oestrogen to control flushes and sweats.

Postmenopausal women are usually offered continuous HT to help minimise bleeding. Even with low-dose regimens, around one-third to half will have spotting and bleeding, at least for a month or two.

There are surprisingly few trials on stopping HT. Most clinicians would treat initially for 2 years and then wean the woman slowly off the HT over 3–6 months, although there is no evidence to support this practice. If flushes return, some will go back on HT—often on a lower dose than initially. A significant minority have great trouble coming off HT, and these are probably the same women who ‘flush forever’.

Risks and benefits of long-term hormone therapy

In the 1990s there was a hope that HT might be a useful long-term preventive agent for women over 50 years of age—reducing heart and fracture risks. However, since 2002, the Women’s Health Initiative (WHI) study has had high media profile, and has caused enormous fear in the community because of a link between HT and breast cancer.

The WHI was an NIH-funded study into strategies to help older women. It had two HT arms, both tested in women whose average age was late sixties. The combined HT arm (Premarin®–Provera®) has been summarised by MacLennan (Table 53.2 and Figure 53.1).²³

TABLE 53.2 Risks and benefits of combined hormone therapy in older women ^*

Adverse effects	Benefits
8 extra breast cancers 7. extra episodes of cardiovascular disease ^** 8. extra cases of pulmonary embolism 8. extra strokes

6 fewer bowel cancers

2. fewer uterine cancers

10. fewer hip & spine fractures

* Risk and benefits after 5 years of combined HT (compared with placebo). All rates are per 10,000 women per year.

** Not statistically significant.

FIGURE 53.1 Risks and benefits of long-term HRT: A After 5 years of combined HRT; B after 7 years of oestrogen-only HRT; C oestrogen-only HRT initiated at age 50–59 years. Complete data for women under age 60 years in the WHI have only been published for the oestrogen-only arm. The WHI was not powered for such subanalyses, as major morbidities are uncommon in this age group. Global index: a global index of risks and benefits.

(from MacLennan 2007²³)

When the WHI data were re-analysed in 2007, to examine risks in the usual age group who take HT—those aged under 60 years—no increased risks were found.²³ It was disappointing that the authors took 5 years to release these data, and unfortunately this important message has not reached the general community. MacLennan also points out that there are emerging data that side effects are reduced by using lower HT doses, minimising systemic progestin exposure by using a Mirena® device, using non-oral HT in some women and initiating HT near menopause.

Several studies have examined the population rates of breast cancer since the decline in HRT use following the release of the WHI data. Breast cancer incidence decline and decreased HRT use showed a high correlation. The decline of breast cancer incidence started about 2 years after the HRT decline.²⁴

The woman who has had a hysterectomy

The woman who has had a hysterectomy and who makes an informed decision to take HT should be treated with oestrogen only. The oestrogen-only arm of the WHI (Premarin® 0.625 mg daily versus placebo) enrolled 10,739 women aged 50–79 years and continued the trial for 7 years. The risk of breast cancer was decreased in the Premarin® arm and a non-significant increased risk of stroke was demonstrated.²⁵,²⁶ There is some evidence of decreased risk of thrombosis with transdermal oestrogen.²,¹⁵

Tibolone

Tibolone is not a traditional HT, but a steroid with oestrogenic, progestational and androgenic actions. Its effect on a target tissue depends on its final metabolism. For example, the endometrium converts tibolone to a progestational metabolite. When given to postmenopausal women, it has a lower rate of breakthrough bleeding and breast pain than standard HT and appears to have no impact on mammographic density, unlike HT, which usually increases breast density.^2,^15,²³ However, weight gain is a common side effect and this tends to limit its appeal.

A randomised placebo-controlled trial of tibolone 1.25 mg (4538 women aged 60–85 years) was published in 2008.²⁷ Women receiving the active treatment had significantly fewer vertebral and non-vertebral fractures and less breast and bowel cancer than the placebo group. However, the tibolone group had a doubled risk of stroke.

The LIBERATE trial ²⁸ randomised 3148 women with breast cancer to tibolone 2.5 mg or placebo. Fifty-eight per cent were node positive, 71% were oestrogen receptor (ER) positive, 67% used tamoxifen and 7% used aromatase inhibitors. Tibolone improved vasomotor symptoms and bone density in this cohort but, unfortunately, it was also associated with an increased risk of metastases. Therefore, tibolone cannot be recommended for women who have had breast cancer.

MANAGING THE WOMAN WHO FLUSHES FOREVER

If a patient is still having significant flushes after 5–6 years, she is probably in the small group who flush forever.² Properly counselled, some of these women will persist with non-pharmacological methods of coping with the symptoms and some will choose to stay on low-dose HT—at least until a better choice is available—and accept the small risks. Theoretically, it may be appropriate to treat these women with transdermal oestrogen (e.g. a dot-patch) to minimise the risk of thrombosis, and consideration should be given to fitting her with a Mirena® device to minimise systemic progestin exposure. However, it should be pointed out that, at the moment, there is no evidence to support such an approach—and there will probably never be such data available.

DEPRESSION AND MENOPAUSE

Feeling sad or blue is a common symptom of menopause, affecting 19–29%, but studies have shown that clinical depression per se is not more common at menopause,² except perhaps for those who have longstanding depression/anxiety. CBT and St John’s wort may assist with mood stabilising. HT might help stabilise the mood of some symptomatic perimenopausal women, but not those who are postmenopausal and flush-free.²

MANAGING GENITOURINARY SYMPTOMS

After menopause, most women will have unpleasant genitourinary symptoms. These include bladder irritability, vaginal dryness, pain during intercourse and recurrent urinary tract infections. Physiologically, after menopause the vaginal epithelium thins dramatically, Lactobacillus disappears, vaginal pH rises from around 4.0 to neutral and the vagina becomes colonised by enteric bacteria.

These symptoms can be managed by the use of non-hormonal moisturisers such as Replens®, avoiding soap (and instead washing with soap-free washes or sorbolene) and the use of lubricants. However, for some the symptoms are so severe that the only real option is oestrogen therapy. Rather than giving HT, topical oestrogens can be tried.¹⁵ There is scant long-term safety data on these products, but there is probably some minimal absorption in the first few weeks of usage while the vaginal epithelium is thin, but little absorption after that.

Vaginal insertion of a Lactobacillus capsule once or twice a week replenishes the vaginal Lactobacillus population and reduces the incidence of vaginal candidiasis.

Continence training with an experienced continence therapist can assist bladder control.

Unfortunately, no CAM has been shown to help genitourinary symptoms.

THE ROLE OF ANDROGENS FOR WOMEN

Testosterone is more abundant in female serum than oestrogen, and serum testosterone levels appear to fall with age, not menopause, unless the ovaries are removed. In blood, testosterone is avidly bound to sex-hormone-binding globulin (SHBG) and only the small ‘free’ fraction is biologically active. Normally, the postmenopausal ovary continues to produce some androgens.² Population studies have failed to link a decline in sexual activity with serum androgen levels. There are also technical problems with the measurement of testosterone. The commercially available assays are designed for the male normal range and not accurate for women or children. In some laboratories, a ‘sensitive testosterone’ assay is available, but even these have poor correlation with sexual desire and responsiveness. Clinical trials have been more helpful than laboratory-based studies.

Oestrogen therapy has been shown to improve vaginal lubrication; even oral HT, despite its adverse effects on SHBG (oral oestrogens increase SHBG levels and so lower free, bioactive testosterone levels), has been shown to improve sexual desire and arousal.² There have been several RCTs of transdermal testosterone for women, usually as patches. In most of the trials, women received adequate oestrogenisation first. These studies have shown a significant improvement in sexual desire and more satisfying sex than placebo. Although serum testosterone levels are of no value in diagnosing hypoactive sexual disorders, they are useful in ensuring that patients are not over-treated, so that androgenic side effects can be minimised. Panay and colleagues published a trial using testosterone patches designed for women without oestrogen replacement, and showed a statistically beneficial effect on sexual desire with minimal side effects.²⁹ It is important to explore possible reasons for low libido before reaching for the prescription pad. These might include relationship problems, emotional issues, over-commitment to responsibilities, and more.

BIO-IDENTICAL HT

Some doctors, working with compounding chemists, ‘hand-make’ hormonal mixtures and call them ‘bio-identical HT’. Typically these treatments are presented as ‘troches’ or lozenges that are sucked, or sometimes prescribed as creams to be rubbed into the skin. They usually contain three oestrogens, progesterone, DHEA, testosterone and sometimes other steroids such as pregnenolone.

Cirigliano has reviewed the scant medical literature on these products.³⁰ These treatments do not undergo stringent quality control, their pharmacokinetics are largely unknown and there are no medium- or long-term safety studies. Often these expensive treatments are monitored using salivary and blood hormone levels that have not been validated.³⁰ It is well known in clinical practice that, unlike monitoring thyroid function, where blood tests are exquisitely sensitive and useful, as already discussed, many of the main symptoms of menopause relate to the brain, rather than blood levels of any particular hormone.

Three cases of uterine cancer were described in Australian women using troches.³¹ The Australasian Menopause Society³² and the North American Menopause Society³³ oppose the use of bio-identical HT, and the medical defence organisations are unlikely to cover the prescribing medical practitioner if there is an adverse patient outcome. However, if a patient has been using this treatment for more than a few months, it may be prudent to perform endometrial surveillance (e.g. transvaginal ultrasound and perhaps an endometrial biopsy ³¹).