Menopause and HRT
ST1 GP, Northern Deanery, UK
E-mail: daniellepeet{at}doctors.org.uk
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Abstract |
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 TOP Abstract The GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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Menopausal symptoms and their management are a common presenting complaint. Due to media hype and inconsistent reporting, there are many misconceptions about hormone replacement therapy (HRT) and alternative therapies. This article outlines the physiology and clinical effects of the menopause and the indications and implications of HRT. It will cover natural and surgical menopause and will not cover other metabolic and genetic causes for ovarian failure.
GPs in training should have a good knowledge base about the physiology of the menopause, its effect on all systems and the indications for HRT as part of the curriculum statement 10.1 ‘Women's health’. Due to the multi-system effect of oestrogen, it requires a knowledge base of prevention of cardiovascular disease, dementia, osteoporosis, endometrial and ovarian cancer. In the curriculum statement, healthy people and within person-centred care, GP trainees should demonstrate an understanding of the concept of risk and be able to communicate risk effectively to the patient and his or her family. Communicating HRT and its risk-benefit profile is a useful case to practise explaining risk to patients.
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What is the menopause? |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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Whether you call it ‘primary ovarian failure’, ‘the climacteric’ or ‘the change’ it, in plain language, is the irreversible end of reproductive life in women. Generally, in western countries, menopause happens between the ages of 46 and 58 with median age 52 years. It is a consequence of progressive depletion of ovarian follicles and is called the menopause from the day of the last period. The premenopausal period can last between 1 and 10 years and it is during this time that women often experience oligomenorrhoea as well as many symptoms derived from oestrogen deficiency. A woman can be called ‘postmenopausal’ after she has not had a period for 12 months. The word ‘climacteric’ is used to describe the transition from the reproductive state to the non-reproductive state.
Every woman experiences menopause differently both in terms of symptoms and the impact on their quality of life. The majority of women (90%) do not seek health professional advice and manage symptoms by themselves. It is also a time when women re-evaluate their employment, family, relationships, finances and children. Lifestyle, demographics and family experience of menopause will affect a woman's perception of the phenomenon and determine their health-seeking behaviour and expectations. Some women feel liberated that they no longer need to worry about becoming pregnant. For others, this fact can be traumatic.
The hallmark symptom of the menopause is hot flushes. In addition to this, many women complain of urogenital symptoms (such as dry vagina and urinary frequency), sexual dysfunction, mood swings and poor sleep, brittle nails and dry skin. Their cycles become longer and more unpredictable. Dwindling oestrogen levels are the cause for these symptoms.
The menopause is also associated with an increase in other chronic conditions. Oestrogen prevents decline in neuronal function and its lower levels in menopause has been suggested to explain Alzheimer's disease being 2–3 times more common in women. The risk of osteoporosis increases after the menopause and oestrogen deficiency causes vascular endothelial dysfunction, thereby increasing the woman's risk of cardiovascular disease. This systemic effect reinforces the importance of treating the patient holistically.
Box 1. Did you know?
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The consultation |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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The initial consultation with women presenting with menopausal symptoms may be challenging due to the amount of controversy and media hype around HRT. Figure 1 outlines the salient features of the first consultation which include the patient's gynaecological history and their individual risk factors.
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How do we investigate it? |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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In response to the reduced number of follicles, the ovary becomes resistant to the gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone (LH) which results in their overproduction by the hypothalamus and subsequently increased levels in the serum. The reduced number of follicles also causes low serum oestrogen. As a consequence, the normal LH surge mid-cycle is disrupted which causes anovulatory dysfunctional menstrual bleeding.
Although a high serum FSH (greater than 30 IU/l) will suggest menopause, it does not indicate severity, when to start treatment or whether a woman is infertile. Therefore, routinely testing FSH is not recommended unless clinically indicated. Other causes for hot flushes and lethargy include thyroid disturbance and anaemia. If the diagnosis of menopause is in doubt, a hormonal profile is reasonable when alongside testing for these differential diagnoses.
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Managing the menopause |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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Key points in Box 2 outline the approach to manage menopausal symptoms. It is a good opportunity during the first consultation with a woman with menopausal symptoms to modify risk factors for cardiovascular disease and osteoporosis and provide general advice on lifestyle to promote good health. The subjective severity of symptoms from the patient will be the deciding factor on whether or not to offer specific treatment.
It is reassuring to know that vasomotor symptoms which start in the perimenopausal period while the women are still having periods disappear in two-thirds of women in a few years. However, these symptoms can be disabling and women may ask for treatment to enable them to stay at work and maintain relationships.
Simple lifestyle advice such as aerobic exercise is often helpful for women who are perimenopausal. It needs to be regularly sustained with cardiovascular workouts as unpredictable exercising can often make matters worse. Equally, reducing intake of alcohol and caffeine can make vasomotor symptoms easier to handle. Weight loss has a significant effect on the frequency and severity of vasomotor symptoms. Stopping smoking will promote general health and reduce the risks associated with medical treatments used in the menopause.
It is good practice to assume that perimenopausal women require contraception. Even if the FSH is high, women are still potentially fertile for 2 years after the last menstrual period if under 50 and 1 year if over 50. Appropriate contraceptives depend on the woman's individual needs. Condoms are often used. Progestogen-only pills can be used throughout the menopausal period with no upper age limit. Use caution when considering the combined pill, using only in women under 50 who are non-smokers and who have no thromboembolic risk factors, cardiovascular disease or liver pathology. The intrauterince system (IUS) can also combat coexisting menorrhagia if this is present.
Box 2. Key points in managing the menopause
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Identifying osteoporosis risk
Box 3 outlines osteoporosis risk assessment. Bone density decreases with age and women should be advised about ensuring that they consume enough dietary calcium, vitamin D and weight-bearing exercise as a primary prevention strategy. Fragility fractures (crush fractures of the vertebra, low impact hip fractures) should prompt us to initiate secondary prevention. Women over 75 should be started on bisphosphonates but if between 65 and 74 should undergo DEXA scanning to establish a diagnosis of osteoporosis (a T score below –2.5) before treatment.
Box 3. Patients at high risk of osteoporosis
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What is HRT? |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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In the 1990s, HRT was widely used offering complete relief from menopausal symptoms while preventing many chronic diseases. After the women's health initiative studies, many adverse effects have prevented its use as simply a prophylaxis against heart disease, osteoporosis and dementia as the risks outweigh the benefits.
Current indications for HRT include hot vasomotor symptoms, night sweats and vaginal dryness. Cochrane reviews have shown a 75% reduction in vasomotor symptoms with therapy compared to 50% reduction with placebo (which is in itself quite interesting). There is no indication for HRT for disturbances of cognition and mood. Urogenital symptoms are more common after the menopause and unfortunately HRT can make incontinence worse. Contraindications for HRT are found in Box 4.
HRT is especially useful in women who have had an early natural or surgical menopause (before the age of 45) because of their high risk of osteoporosis. Figure 2 summarizes the HRT options available.
HRT comes in tablets, topical preparations for local use, transdermal patches, gels, nasal sprays and implants; there is no convincing evidence to support one route over another. It has been suggested that patches, delivering oestrogen transdermally, have a lower thromboembolic risk profile but further research is required to quantify this. Implants are best left to the specialists and are usually reserved for women who have had an early surgical menopause.
Menopausal atrophic vaginitis can cause a dry vagina and painful intercourse. Gels for vaginal symptoms allow pain-free intercourse and reduce the incidence of urinary infections. Gels such as Replens, a vaginal bio adhesive moisturiser, are a more physiological way of replacing vaginal secretions compared with lubricant vaginal gels such as KY jelly. Topical oestrogen (Trieste cream) can improve vaginitis also. Response to topical HRT can take months to develop and often these treatments are needed long term. Systemic absorption is minimal so risk from oral HRT does not apply and patients do not need to use progestogen alongside.
Women with a hysterectomy can use unopposed oestrogens but remember that women with a womb are at risk of endometrial hyperplasia and potential malignant transformation. There is no need to routinely investigate the endometrium prior to commencing HRT unless there is a clinical indication. The progestogen can be delivered via tablets (e.g. norethisterone, levonorgestrel) or by using the IUS mirena coil.
Combined continuous regimens containing both oestrogen and progestogen are best used for postmenopausal women only as use of this type of HRT in women still ovulating, albeit erratically, can cause irregular bleeding. Cyclical HRT is used for women having periods, oestrogen should be started on the first day of the menstrual period and progestogen given 14 days later hopefully followed by a withdrawal bleed. Thankfully, there are many user-friendly starter packs on the market. The list in the British National Formulary (BNF) is huge so the best thing is to check your surgery's formulary.
Box 4. Contraindications as HRT will increase disease
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The risks of HRT |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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The Women's health initiative (WHI) study included women aged 50–79 using oestrogen alone or with medroxyprogesterone. Results (Table 1) showed a statistically significant increase in stroke, deep vein thrombosis (DVT) and gallbladder disease for both arms of the trial. It showed additional increases which were not statistically significant in breast cancer (Table 2) and dementia.
Conversely, there were statistically significant benefits. Fractures were reduced significantly with both oestrogen alone and the combined treatments if used long term and colorectal cancer was reduced in the combined HRT group.
Breast cancer is increased with all types of HRT within 1–2 years of initiating treatment. The longer the duration of treatment the risk increases, but thankfully the individual risk returns to that of the population after 5 years of discontinuing treatment. Table 2 gives the statistical data which is useful in explaining risks to patients.
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The increased risk of endometrial cancer depends on dose and duration of oestrogen only HRT. It is significant (32 more women in every 1000 over 10 years) and the evidence behind the use of progestogen cover in women with an intact uterus.
Most of the literature says ‘use the lowest dose of hormone for the shortest duration to give symptom relief’. The risks as stated above are likely to be lower for healthy perimenopausal women using lower doses of hormone and are often acceptable risks in women with very troublesome symptoms.
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Follow-up |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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Once started on HRT, the woman should be reassessed 3 months later and annually thereafter if there are no complications. At each visit check the woman's blood pressure, bleeding pattern and weight. Assess the effectiveness of therapy and ask about side effects. Ensure the woman is examining her own breasts and if there is a family history of breast cancer; consider examining the patient's breasts at each annual visit.
Common side effects related to oestrogen in HRT include nausea, breast tenderness, leg cramps and headache which often improve after 3 months of treatment. If side effects are persistent consider reducing the dose of HRT or changing to a lower oestrogen content. Side effects caused by the progestogen content include mood swings, bloating, fluid retention and weight gain.
Increase in bleeding when using cyclical regimes may be related to the therapy and may respond to increasing the duration and dose of the progestogen content. The IUS would be a good way of delivering progestogen in idiopathic menorrhagia.
Bleeding when using continuous therapy in postmenopausal women is common in the first 3 months of therapy. Breakthrough bleeding beyond this time or spotting after a period of amenorrhoea is suspicious and should be investigated as per guidance for postmenopausal bleeding (i.e. visualize the cervix, abdominal exam and ultrasound to measure endometrial thickness)
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When should HRT be stopped? |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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In the UK, half of women will discontinue HRT after 1 year. There is no rule of thumb regarding stopping HRT but current advice is to stop within 1 or 2 years to see if symptoms have gone. If symptoms recur, the options are to either introduce therapy for specific symptoms (e.g. clonidine for vasomotor symptoms) or restart the HRT at a lower dose. HRT should be reviewed annually.
It is a good practice to stop HRT 4–6 weeks prior to any major surgery involving a general anaesthetic to reduce the risk of venous thromboembolism
A woman who started on HRT for early menopause should stop it at the time she would otherwise expect to stop her periods (e.g. 50 years).
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Alternatives to HRT |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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Many women will come to their GP to discuss alternatives to the traditional HRT medical treatment. More recently, the press have picked alarming statistics from clinical trials over emphasizing the risks of taking HRT such as breast cancer, heart disease and stroke. The efficacy of alternative preparations appears to be lower than with traditional HRT—50–60% compared with 80–90% with traditional HRT.
Some women want ‘natural’ remedies and it is important to communicate the evidence base (see Table 3) of the options to enable them to make an informed choice. The key message is that some herbal potions marketed for the menopause which have not been regulated by a governing body can contain oestrogenic compounds which are not included in their advertisements. The Royal College of Obstetricians and Gynaecologists (RCOG) has published an excellent guideline using all of the most recent data in a way patients can understand. Women could in fact be taking more hormones than they would with tried and tested HRT. This is alarming as the medication could be interacting with warfarin and anti-epileptics and also altering the prognosis for women with hormone-dependent disease like breast cancer.
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Medical alternatives to HRT include
- Tibolone, a synthetic steroid with weak oestrogenic, progestogenic and androgenic properties can help with vasomotor symptoms. It is limited as the risk of breast cancer and heart disease are unclear with the limited data available. Using progestogens can improve vasomotor symptoms and are especially useful in patients who cannot take oestrogens (DVT or breast cancer).
- Weak evidence has shown that clonidine, a centrally active alpha 2 agonist, helps with vasomotor symptoms and is especially useful in patients with a history of breast cancer. Clonidine can enhance the effect of anxiolytics and alcohol and should be withdrawn gradually due to a risk of malignant hypertension.
- Consider selective serotonin reuptake inhibitors (SSRIs) as they can reduce vasomotor symptoms 60% compared to placebo 30% according to studies evaluated in the RCOG guidance. This is probably due to serotonin being involved in aetiology of vasomotor symptoms. Watch for dry mouth, dizziness, nausea, constipation and reduced libido. It is important to stress that this treatment is for the menopause and not for depression.
- Gabapentin reduces hot flush frequency by 45% and symptom severity by 54%.
Complementary therapies
There is epidemiological evidence that a diet high in isoflavones and soy (e.g. in Japan) reduces the severity and frequency of vasomotor symptoms, cardiovascular disease, osteoporosis, breast cancer, colorectal cancer, endometrial cancer and ovarian cancer. Meta-analysis have so far shown conflicting evidence and there is still research required to determine the exact objective symptoms and bioavailability of isoflavones in food. There are no safety concerns regarding soy dietary supplements.
Dihydroepiandrosterone (DHEA) (dehydroepiandrosterone) is being marketed as a food supplement in the USA. It is the precursor steroid hormone to the sex hormones and is broken down into oestrogen and testosterone in the body. Some evidence has shown better cognition, increased libido and improved atrophic vaginitis. However, there are no known risks of its long-term use. It has several worrying side effects including cholestatic jaundice and can cause breast enlargement and fluid retention. Other alternative treatments for menopausal symptoms that have been studied include.
- Patients taking red clover showed an improvement of symptoms in two of five studies. Again there are no health concerns from taking red clover dietary supplements
- A recent randomized controlled trial showed black cohosh improved vasomotor symptoms. It has recently been certified by the German medicines control agency. It has an estrogenic-like effect centrally to improve the deficiency. It is relatively safe with one reported case of hepatitis
- Studies looking at vitamin E show a small non-statistically significant reduction in vasomotor symptoms
- There is no evidence of efficacy of evening primrose oil although this is widely used for menopausal symptoms
- Do not use testosterone. It does improve sexual function but its long-term effects are uncertain
- Agnus castus or chasteberry shows reduction of premenstrual syndrome in some studies but is not helpful in menopause
- A trial showed no statistically significant difference between two groups of foot massage and reflexology
- Observational studies assessing the effect on daily living with a small number of participants show a small benefit from homeopathy. More research is required to assess its full effects
- Some studies show improvement of symptoms of anxiety and depression with Ginkgo biloba
- Ginseng, a perennial herb in Korea and China improves feelings of well-being and depression
- Dong quai, a traditional Chinese medicine derived from a perennial Chinese plant, has been shown to have no benefit. It contains coumarins and therefore interacts with warfarin.
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How best to empower women to choose? |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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The menopause is an inevitable fact every woman will have to face in their lifetime. First, be aware of simple lifestyle issues which can have major effects on symptoms. HRT is statistically more effective than many of the alternatives but carries added risks. We need longer studies to determine long-term effects and how HRT is metabolized in ethnic groups. More research is needed on the complementary therapies to strengthen the data to allow us to advise patients appropriately and to allow us to prescribe at a standardized dose. Legislation is being put into place to ensure herbal preparations with robust data that can be registered with the Medicines and Healthcare Products Regulatory Agency (MHRA) to ensure over the counter products can be controlled. This in effect will provide GPs and their patients with affordable alternatives to HRT that actually work.
Key points
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References |
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TOPAbstractThe GP curriculum, menopause...What is the menopause?The consultationHow do we investigate...Managing the menopauseWhat is HRT?The risks of HRTFollow-upWhen should HRT be...Alternatives to HRTHow best to empower...References |
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Balasch J. Sex steroids and bone: current perspectives. Human Reproduction Update (2003) 9(3):207–222.
Biglia N. Management of risk of breast carcinoma in postmenopausal woman. Endocrine-Related Cancer (2004) 11(1):69–83.[Abstract]
Genazzani AR, Pluchino N, Luisi S, Luisi M. Oestrogen, cognition and female ageing. Human Reproductive Update (2007) 13(2):175–187.
Markou A, Duka T, Prelevic GM. Oestrogens and brain function. Hormones (2005) 4(1):9–17.[Medline]
Melby K, Lock M, Kaufert P. Culture and symptom reporting at menopause. Human Reproductive Update (2005) 11(5):495–512.
National Institute of Health (NIH) The Women's Health Initiative Study. Accessed via www.nhlbi.nih.gov/whi/whi_faq.htm [date last accessed 09.11.2008].
Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. Journal of the American Medical Association (2002) 21:872–881.
NHS clinical knowledge summaries Website: www.CKS.library.nhs.uk.
Prelevic G. Hormone replacement therapy in postmenopausal women. Minerva endocrinology (2005) 30(1):27–36.
RCGP. GP Curriculum statement 10.1: Womens health. Accessed via www.rcgp-curriculum.org.uk/PDF/curr_10_1_Womens_Health.pdf [date last accessed 26.08.2008].
Roberts H. Managing the menopause. British Medical Journal (2007) 334:736–741. Accessed via www.bmj.com/cgi/reprint/334/7596/736 [date last accessed 26.08.2008].
The British Menopause Society Website: www.thebms.org.uk.
The Royal College of Obstetricians and Gynaecologists Website: www.rcog.org.uk.
The Royal College of Obstetricians and Gynaecologists. Alternatives to HRT for management of symptoms of the menopause (2006) Available via www.rcog.org.uk/resources/public/pdf/alternatives_to_hrt_sac_paper6.pdf [date last accessed 09.11.2008].
Vermeulen A. Environment human reproduction menopause, and andropause. Environmental Health Perspectives (1993) 101(Supplements):91–100.
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