Need to know - managing the menopause

1. What are current recommendations on use of HRT in early postmenopausal women?

The majority of women (that is, those with an intact uterus) will need a sequential preparation of HRT – one containing continuous oestrogen and 12 days of a progestogen – if they are within one year of their menopause. Those who are clearly one year past their final menstrual period can take a continuous combined preparation. These are not totally bleed-free and up to 50% of patients can expect some kind of spotting in the first year of use.

Any heavier bleeding must be regarded as pathological and investigated. A good alternative is to fit a levonorgestrel IUS. This gives excellent endometrial protection and oestrogen alone can be given for HRT. Those who have had a hysterectomy can similarly have oestrogen-only preparations unless there is a contraindication such as pre-existing endometriosis, when a continuous combined form should be used.

2. How much should a family history of breast cancer in a first-degree relative influence our prescribing of HRT for early postmenopausal women?

There has been a huge amount of adverse publicity in the last few years linking HRT to an increased chance of developing breast cancer. Not surprisingly, women with a family history of breast cancer (6-19%) are often most reluctant to start on HRT. This association may be just chance, may be caused by outside factors or be genetic.

However, most geneticists will not investigate women with only one first-degree relative for inherited mutations of the BRCA 1 and 2 genes. These women may or may not be at greater risk of breast cancer, which leaves the GP in a quandary.

The Women’s Health Initiative (WHI) study of women taking continuous combined HRT showed an increased chance of developing the cancer of 0.8/1,000 women/year, or four extra cases for every five years of therapy per 1,000 women. This is against a background of 45 women per 1,000 getting the disease between the ages of 50 and 70.

Paradoxically, the WHI study showed no increase in the incidence of breast cancer in women on oestrogen-only preparations and it would be interesting to know whether this could be applied to those women with a Mirena in situ (there is no available information on this). Therefore careful counselling is needed and symptoms and general quality of life issues taken into account. There are non-hormonal alternatives (see below) but HRT remains the most effective for control of symptoms.

3. At what average age should we start to think about stopping HRT and how long should we recommend patients take HRT for?

The Chief Medical Officers of England and Wales recommended that HRT should be for short-term use but failed to define what this was. An RCOG Study Group published their findings in Menopause and Hormone Therapy (RCOG Press, 2004) and suggested that ‘short term’ should be for five years.

This, of course, does not apply to those with premature ovarian failure (before age 45) who should be encouraged to take HRT until they are 50 and then make an informed decision as to whether to continue.

There is no specific time when risks outweigh advantages and each woman must be treated on an individual basis. For some, much longer therapy might be appropriate.

4. For which postmenopausal women should we recommend raloxifene to prevent or treat osteoporosis or reduce the risk of breast cancer?

Raloxifene is a selective oestrogen receptor modulator (SERM), like tamoxifen. It has a very strong affinity to oestrogen receptors in the breast and is as effective as tamoxifen.

However, unlike tamoxifen, it has a strong effect on bone metabolism, increasing bone density and preventing the progression of osteoporosis. It has no effect on the endometrium (unlike tamoxifen, which stimulates it) but both are associated with an increase in vasomotor symptoms, vaginal dryness and an increased rate of DVT. In asymptomatic postmenopausal women, raloxifene can be a useful therapy in those at risk of fracture and who cannot or will not use HRT.

5

. How effective are other drugs in treating menopausal flushes?

Nothing is as effective as HRT in treating vasomotor symptoms. Clonidine, an a-adrenoceptor agonist used for the treatment of hypertension, has been used for the relief of hot flushes but there have been no satisfactory randomised trials that show it to be as effective or of value.

There is evidence that SSRIs such as venlafaxine, paroxetine and fluoxetine are effective in controlling hot flushes but there is insufficient evidence to support long-term use. Gabapentin, more commonly used as an anti-epileptic or for the treatment of neurogenic pain, is effective but side-effects may preclude its use.

Progestogens are effective and megestrol acetate has been used widely in women with breast cancer. Its mode of action might be due to conversion into oestrogen by the body. Long-term studies have not been carried out.

Dihydroepiandrostenedione (DHEA) is marketed in the US and on the internet as an anti-ageing agent. It has no known use at the menopause. Progesterone transdermal creams are now available but there is insufficient data to recommend their use.

Some women have tried to avoid the side- effects of progestogens taken orally by using the cream, but there is no evidence that the creams can induce secretory changes in the endometrium and women using oestrogen with a progesterone cream are at increased risk of endometrial cancer.

6. How safe are herbal remedies?

Herbal remedies remain popular. The most effective for reducing flushes are phyto-oestrogens, which are found in soya, red clover and yam.

These isoflavones have been shown to have a positive effect in the short term. Much interest has been shown in Japanese women, who have a high soya bean diet rich in isoflavones. The incidence of menopausal symptoms seems to be much lower in the Far East but, paradoxically, the Japanese communities on the west coast of the US, who have a similar diet, have similar menopausal symptoms to their Caucasian counterparts.

Herbs need to be used with caution as some may interact with drugs. Gingko can cause bleeding when taken with warfarin, and hypericum can react with SSRIs. Kava kava (banned in the UK) may be effective but liver damage has been reported.

Ginseng and dong quai have not been shown to be effective in randomised trials and this applies to evening primrose, St John’s wort, Agnus castus and valerian.

Black cohosh is widely used to help with flushes, and short-term trials have been promising but little is known about long-term toxicity. Traditional Chinese medicines contain a large variety of substances, some of which may be toxic and cannot be recommended. At present there is little control over herbal medicines and the quality of the products.

7. Is there any evidence for the use of magnets or other alternative treatments?

There is little evidence that magnets worn around the pelvic area have anything more than a placebo effect. Homeopathy is popular and anecdotal evidence among proponents suggests it is useful but more properly conducted research is needed.

Acupuncture has been disappointing for the control of menopausal symptoms, although it is widely practised. Other remedies include reflexology, Ayurveda, Reiki and aromatherapy. They may lead to relaxation and a sense of wellbeing, but evidence of long-term benefit is missing.

8. How safe is low testosterone therapy in women who have had oophorectomy? Should we monitor lipid levels or do LFTs? What are the relative risks and benefits compared to testosterone implants?

Testosterone has been used for loss of libido for many years in the form of implants. The amount delivered is small and androgenisation is rare but the implants must be used in conjunction with an oestrogen.

The latter increases sex hormone binding globulin (SHBG) and inactivates much of the circulating free testosterone. There is no benefit in monitoring testosterone levels and no need to test liver function or lipid levels.

Recently, testosterone patches have come on the market. The licence only covers those who have undergone surgical oophorectomy and who have hyposexual desire disorder (HSDD) – a loss of libido that causes distress – and where other causes have been excluded. Evidence suggests the patches significantly increase sexual desire.

The advantage of the transdermal route is that steady levels of hormone are maintained compared with implants where there is an initial sharp rise in levels and a gradual decline over a six-month period.

9. What should we recommend for postmenopausal loss of libido?

Changes in sexual behaviour are common around the menopause. There may be many reasons for a decrease in sexual activity. Lack of oestrogens may lead to vaginal dryness and dyspareunia. Also there is a change in body shape and weight is gained, which may lead to decreased self-image and feelings of sexual inadequacy.

Non-hormonal factors such as insomnia, stress, depression and so on can lead to a loss of sexual feeling. However, oestrogens are mood enhancing and will obviously help problems that are directly related to the hormonal changes of the menopause.

Tiredness, lack of energy and a general sense of a diminution in wellbeing have been attributed to loss of testosterone at the menopause. There has been considerable anecdotal evidence to recommend testosterone supplementation, but transdermal patches are only licensed for those who have had oophorectomy.

10. How long after the menopause do women have problems with vaginal atrophy? Can this contribute to urinary symptoms?

The reduction in oestrogen levels at the menopause leads to a loss of collagen in the tissues and this causes vaginal ‘shrinkage’ and dyspareunia. If the woman remains sexually active, the effects are lessened.

In addition the loss of oestrogen leads to loss of glycogen in the vaginal epithelium. Lactobacilli in the vagina, which depend on the glycogen, disappear and the pH of the vagina increases. This can lead to bowel bacteria invading the vagina and urethra, and an increase in urinary tract infections.

In addition there is narrowing of the urethra and shrinkage of the bladder trigone, which leads to frequency, urgency and nocturia. In some cases, dysuria may also be present despite no evidence of bacteriuria. Antibiotics will not help.

11. Who benefits from oestrogen rings?

At present the only oestrogen ring on the market is a topical one. This can remain in situ for up to three months and is particularly suitable for the elderly with persistent urinary problems and those with atrophic vaginitis. Other topical oestrogen preparations such as pessaries, creams and tablets are equally useful.

12. Should women using vaginal oestrogens who have not had a hysterectomy be prescribed a progestogen to protect the endometrium?

Topical vaginal oestrogens are not absorbed systemically and confer no benefits except directly to the vagina. They do not cause endometrial proliferation so a progestogen is not needed.

Although the manufacturers recommend a maximum of three months, there is no evidence that longer therapy causes untoward effects. Personal experience of long-term therapy backed up with annual ultrasound scanning of the endometrium confirms this.

Mr Peter Bowen-Simpkins is consultant obstetrician and gynaecologist at Singleton Hospital, Swansea, and a council member of the Royal College of Obstetricians and Gynaecologists

Competing interests Mr Bowen-Simpkins recently received a fee from Proctor and Gamble, manufacturer of Intrinsa, for giving a lecture on androgen therapy for women

Dr Pam Brown is a GP in Swansea

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Story date 18 Feb 08

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