“Recent surveys show that people being treated for schizophrenia consider sexual dysfunction to be one of the most intolerable side- effects of antipsychotic medication (Hellewell, 2000; Rethink, 2002). Historically, mental health nurses may have shied away from discussing sexual difficulties, either through embarrassment or for fear that acknowledging a link with medication might affect compliance. A better understanding of anti-psychotic medication and its effects along with a more rational and collaborative approach to treatment can, however, enable nurses to help people overcome medication-induced sexual difficulties. This will, of course, require skill and sensitivity. First, though, they must be armed with an understanding of some of the physiology involved in this problem. This article by Shubalade Smith and Tony Gillam will, therefore, explain the physiological effects of prolactin before going on to explore the implications of this knowledge for mental health nurses
Dopamine is the main prolactin inhibitory factor and most antipsychotic drugs work primarily as dopamine 2 receptor-blocking agents. Prolactin is secreted by the anterior pituitary gland and the control is regulated by the hypothalamus via the secretion of dopamine. Any disruption of the anterior pituitary gland may result in excessive secretion of prolactin, termed hyperprolactinaemia.
This dopamine-blocking property is fairly non-specific with most anti-psychotics, yet it is thought to account for their antipsychotic activity. Thus the desired action of these drugs – blockade of limbic dopamine receptors – is offset by blockade in other areas of the brain accounting for the distressing movement side-effects and the hyperprolactinaemia that are commonly seen with these medications.
Raised prolactin levels
When under the inhibitory control of dopamine, prolactin usually remains within normal limits. However, prolactin increase can be caused by a variety of physiological factors including pregnancy, breast-feeding, stress, pain, following an epileptic seizure and exercise. Prolactin levels also vary during the day, with maximal levels being secreted in the early hours of the morning.
In animals, prolactin is responsible for sexual behaviour. Very little is known about the normal physiological role for prolactin except that it is the hormone responsible for lactation in breast- feeding women.
Hyperprolactinaemia is a concern for mental health nurses because there is a relationship – not necessarily a causal one in all cases – between hyperprolactinaemia and various aspects of physical health. These include:
* Sexual and reproductive dysfunction
* Weight gain
* Breast cancer
* Bone mineral density and osteoporosis
* Cardiovascular problems
Any changes in physical health are likely to impact psychologically and socially on the individual and it is essential that the mental health nurse knows something of the physiological effects of hyperprolactinaemia, which are detailed in turn below.
Anti-psychotics and reproductive function
Hyperprolactinaemia secondary to pathological causes such as a pituitary tumour is commonly associated with sexual dysfunction including low libido, erectile and ejaculatory dysfunction in men, vaginal response abnormalities and difficulty achieving orgasm in women. In addition, hyperprolactinaemia is a common cause of infertility secondary to the hypogonadism (low levels of gonadal hormones, i.e. low oestrogen, progesterone and testosterone) that it can induce. This hypogonadism may increase the risk of low bone mineral density and subsequent osteoporosis. Despite the well- documented effects of raised prolactin, the effects of antipsychotic- induced hyperprolactinaemia are not well known (Biller; 1999 Lim, 1987; Colao et al, 1996)
Recently studies have shown that far from being a benign side- effect of antipsychotic treatment, hyperprolactinaemia may cause profound sexual and reproductive dysfunction in both men and women. It is associated with menstrual irregularities and infertility in women and this puts them at greater risk of osteoporosis (Smith et al, 2002a; Smith et al, 2002b).
The same studies show that patients taking long-term antipsychotic medication have prolactin levels that exceed the upper limit of normal. This finding was more pronounced in women compared with men. When gonadal function was assessed, this gender difference was significantly greater, with 85% of women showing inadequate gonadal function compared with only 6.4% of the men. It is of note that 40% of the women reported normal menstrual cycles, yet only 85% of these were not actually ovulating. Thus even normal periods are not a guarantee of normal reproductive functioning in women taking anti-psychotic medication. For women, there was a significant, inverse relationship between prolactin and endocrine measures. This suggests that hypogonadism is associated with anti-psychotic- induced hyperprolactinaemia. This hypothesis is supported by the lack of correlation between endocrine function and age in women (ibid).
Anti-psychotics and sexual dysfunction
The true incidence of sexual dysfunction associated with anti- psychotic medication may be underestimated because patients, in particular women, may be reluctant to report these events spontaneously (Harrison et al, 1986). As a result, sexual dysfunction is underestimated in the management of patients on long- term anti-psychotic treatment.
A survey by Rethink (formerly the National Schizophrenia Fellowship) found that patients felt sexual dysfunction was one of the most intolerable side-effects of anti-psychotic medication (Rethink, 2002). This is a similar finding to Hellewell et al (2000), who found that patients rated sexual dysfunction as one of the worst side-effects of anti-psychotics, yet mental health professionals rated sexual dysfunction as being much less troublesome to patients than this.
The effects that these medications have on sexual and reproductive function appear to be quite profound, yet studies (Tran, 1997; Beasley, 1997) that rely on spontaneous reporting of these side-effects tend to report low levels of these problems. If patients are asked directly about these side effects, they report high levels of sexual dysfunction and, perhaps more importantly, feel that sexual dysfunction is the most troublesome side-effect of anti-psychotic medication.
Sexual dysfunction occurs in almost 50% of patients taking anti- psychotic medication. In men it is most likely to be caused by the autonomie side-effects of the anti-psychotic, unless the man becomes hyperprolactinaemic, in which case, this will override any other causes and be the main cause of his sexual dysfunction. In women, hyperprolactinaemia is the main cause of the sexual dysfunction identified (Smith et al, 2002b).
Anti-psychotics and weight gain
There is evidence to show that hyperprolactinaemia induced by antipsychotic drugs may be one of the causes of weight gain that is seen in patients with chronic psychosis (Baptista et al, 1997a; Baptista et al, 1997b; Baptista et al, 2001). This is thought to be a direct metabolic effect of the hyperprolactinaemia rather than being an indirect effect e.g. via increasing appetite. The consequences of this are that patients may put on weight with certain prolactin-raising antipsychotics even if they have a healthy, balanced diet. This problem may be more noticeable in women. Traditionally, where patients have complained of weight gain, nurses have resorted to encouraging a healthier lifestyle, discussing diet and exercise with the patient, perhaps even making a referral to a dietician. Though a healthier lifestyle can obviously do no harm the frustrating fact remains for both nurse and patient that, despite both parties’ best efforts, this strategy alone may not solve the problem.
Anti-psychotics and breast cancer
There is evidence that patients with breast cancer have hyperprolactinaemia and this is thought to be a consequence of breast cancer cells secreting prolactin ectopically (Bhatavdekar et al, 2000). As yet there is no firm evidence linking hyperprolactinaemia causally to breast cancer in humans, although research in rats shows an increased rate of tumour growth in hyperprolactinaemic animals (Welsch et al, 1975). More research is required to ascertain whether being in a long-term hyperprolactinaemic state, as is the case with many patients with serious mental illness, is associated with a greater incidence of breast cancer.
Anti-psychotics and bone mineral density
Osteoporosis is now recognised as a major health problem world- wide and it is increasing due to greater life expectancy. The risk of osteoporotic fracture in white women at the age of menopause is 30-40%. Over two million people in the UK suffer from osteoporosis now, but that figure could double in the next 20 years. All other conditions associated with chronic states of low blood oestrogen have associated bone loss changes (for example, anorexia nervosa sufferers and post-menopausal women). The Department of Health (1998) recommends that both females with long-term amenorrhoea and hypogonadal males should be considered at high risk of osteoporosis. Disorders where females have never menstruated (primary amenorrhoea) are associated with extreme oestrogen deficiency, severe osteoporosis and high fracture rates (Davies et al, 1995). Disorders with infrequent menstrual cycles ar\e associated with reduced bone mineral density (BMD) (Adami et al, 1998). In situations where prolactin is either pathologically elevated (prolactin-secreting tumours) or physiologically elevated (breast-feeding women), menstruation is suppressed, and BMD is reduced (Caird et al, 1994). It is thus very likely that women on neuroleptic medication with hyperprolactinaemia and hypoestrogenaemia have decreased BMD. Recently this has been confirmed by studies, which show that anti- psychotic medication is indeed associated with low bone mineral density and that prolactin levels are particularly important in this respect (Meaney and O’Keane, 2002; Howes and Smith, 2002).
Anti-psychotics and the cardiovascular system
In pre-menopausal women, oestrogen is known to be cardio- protective, i.e. it reduces the likelihood of a cardiac event such as a myocardial infarction. This cardio-protection is lost in postmenopausal women who have low levels of oestrogen and their risk of developing cardiac disease increases to a level similar to men. It may be that the hypogonadal state induced by anti-psychotic medication (this refers to long-term antipsychotic administration i.e up to one year) represents a chronic loss of oestrogen and thus a chronic loss of the usual cardioprotective factor in females. As yet there has been no formal research into the effects of prolactin- raising anti-psychotics on cardiac function in women. This is an area for concern.
The effects of the atypical anti-psychotics on prolactin secretion
A typical antipsychotic drugs work differently to typical traditional antipsychotics, in that they have high affinity for both serotonergic and dopaminergic receptors. Some of these newer atypical antipsychotic drugs (olanzapine and ziprasidone) cause only transient rises in prolactin. Quetiapine and clozapine are, indeed, prolactin-sparing and therefore much less likely to cause the high levels of prolactin seen with traditional neuroleptics.
Hyperprolactinaemia and its effects on compliance with medication
With the advent of the newer atypical antipsychotic medications, comes the possibility of improving compliance by reducing distressing side effects. Discontinuation of drug treatment in schizophrenia is associated with a 96% chance of relapse at two years (Gitlin et al, 2001). The costs of this in terms of individual, family and social distress, not to mention economic costs, are huge. Even treatment with clozapine, the most expensive atypical anti-psychotic drug is cheaper than the cost of protracted in-patient care (Aitchinson and Kerwin, 1998). Atypical anti- psychotics are as effective as traditional anti-psychotics yet have a better side effect profile. Minimal sustained effect on prolactin is one of the distinguishing characteristics of atypicals.
The fact that conventional neuroleptics cause hyperprolactinaemia means that the propensity for them to cause sexual dysfunction is high. We have seen that patients feel that sexual dysfunction is one of the most unacceptable side-effects of anti-psychotic medication. Unfortunately, patients seem unlikely to spontaneously report sexual difficulties and clinicians seem equally unlikely to ask. The newer atypical anti-psychotic agents tend not to have profound effects on prolactin and are thus less likely to cause chronic hyperprolactinaemia and the reproductive dysfunction associated with it.
Giving patients opportunities to discuss their health beliefs and sharing information about drug effects and side effects may reduce the likelihood of non-compliance with treatment. In addition, the prescribing of medication that is less likely to produce sexual side- effects will go a long way to alleviating a patient’s concerns. It would be helpful if discussion of the patient’s current sexual life became a routine part of the therapeutic intervention, thus establishing that any sexual problems can be discussed with clinicians. Apart from normalising and removing some of the associated embarrassment, this could also help provide a baseline assessment of sexual function and menstrual history prior to commencement of medication.
For patients with suspected hyperprolactinaemic-induced sexual dysfunction, reduction of dose may produce an improvement as this is usually a dose-related phenomenon. An even better option might be to change to a drug less likely to raise prolactin, or to switch to a prolactin-sparing antipsychotic. It is important to remind patients that following a change in medication, particularly to a prolactin- sparing medication, their fertility may return to normal and they will need to decide what they wish to do regarding contraception.
It could be argued that in view of the inevitability of hyperprolactinaemia with conventional neuroleptics and the very high likelihood of a resultant gonadal dysfunction, prolactin-sparing anti-psychotics should be used first-line in all new patients with psychotic illness. This reduces the risk of cardiovascular disease and osteoporosis in a group which is already likely to suffer poorer physical health. It is recognised, for instance, that people with severe mental illness – perhaps because they may tend to smoke heavily, follow a less healthy lifestyle in terms of exercise and diet and present later with physical illness – have extremely high death rates from common physical illnesses like heart disease and cancer (Department of Health, 1992).
Implications for mental health nurses
There is insufficient space in this article to explore the nursing implications of all the possible effects of hyperprolactinaemia. Reproductive function, weight gain, the potential risks of breast cancer and effects on bone mineral density and the cardiovascular system have all been mentioned briefly. This article has emphasised the nurse’s role in relation to sexual dysfunction taking, as its starting point, the disparity between the relative importance placed on this by patients and by nurses (Hellewell, 2000; Rethink, 2002). Compliance with treatment is another important area that has been considered briefly but is worthy of further exploration, particularly in the climate of supplementary prescribing by nurses and the increasingly systematic monitoring of side effects by nurses (using tools such as the Liverpool University Neuroleptic Side-Effect Rating Scale [LUNSERS]).
While sexual function can be seen as a purely biological symptom requiring biological management, mental health nurses are likely, with their bio-psychosocial model of health, to posit the problem in its psychosocial context. This may mean, for example, taking into account questions of sexuality. Psychiatry has a chequered past in matters of sexuality, particularly in its attitude to gay people, and mental health nurses should be aware of this. Homosexuality is no longer – as it once was -viewed as a psychiatric disorder in its own right; however, mental health services are not necessarily neutral in their treatment of gay people. Gay women, for example, have reported that their sexual orientation is ignored, viewed as the cause of their problems or seen simplistically as the result of factors such as sexual abuse (Project for I Advocacy, Counselling and Education [PACE] 1998).
Many mental health nurses will be conscious of a seemingly disproportionate number of patients having been victims of sexual abuse. While it is unlikely to be a new phenomenon in our society, it is only since the late 1980s that sexual abuse has begun to be recognised as more prevalent that had previously been thought. It would seem, from surveys, that one in eight women is a victim of sexual abuse in childhood with the figure rising to as much as 50 per cent in women who use mental health services (Johnstone, 2000). It is not only women who are affected. Men who were sexually assaulted either as children (an estimated one in 20) or as adults (around three per cent) are very much more likely to end up in contact with mental health services (ibid). Great sensitivity is needed when discussing sexual matters as victims of abuse may experience this, not merely as embarrassing or intrusive, but as abusive in itself.
Sexual dysfunction is, in one sense, an individual’s difficulty but, where that individual is in a relationship or seeking to be in a relationship, it becomes a shared difficulty. Patients may want the nurse to discuss the difficulty, and practical solution to it, with their partners present and mental health nurses may find themselves being drawn into sexual health counselling or impromptu conjoint or marital therapy – roles for which they may not feel well equipped.
There are obvious implications for professional training and supervision arising from this. No doubt nurses have always found themselves in therapeutic relationships where patients have confided in them their concerns over intimate physical and psychological problems. In this sense, facilitating discussion about sexual dysfunction is nothing new. What is different is that, given our growing awareness of sexual dysfunction relating to antipsychotics, mental health nurses are now being encouraged to highlight these concerns, and for their responses to be evidence-based. Rather than offering mere reassurance or suggesting the patient sees their GP, the onus is now on the nurse to consider the problem in the light of optimal medication, treatment compliance and the psychosocial context of the patient. Mental health nurses may, therefore, increasingly need not only good information about medication and its side effects, including hyperprolactinaemia, but a greater willingness to discuss sexual matters. Training and supervision will, in turn, need to address sexuality, how to support victims of abuse and how to work, not only with individuals but, at times, with individuals and their partners, whilst maintaining professional standards of confidentiality.
There is also a question of matching the gen\der of the nurse to that of the patient. This is not to say that all female patients should have female nurses and all male patients male nurses. First, this is probably unmanageable in most adult mental health services. second, there are female patients (even some who have suffered sexual abuse) who prefer to talk to a male mental health nurse, while female nurses may not always feel comfortable dealing with male patients’ complaints of sexual dysfunction. A sensible approach would be, at the least, to take into consideration the needs and preferences of patients and to attempt to be flexible in allocating individuals to different members of the team.
As with most questions in mental health care, in response to the problem of sexual dysfunction there is both a simple and a complex answer. At its simplest, the mental health nurse’s intervention might involve reassuring the patient that there is something that can be done to help. Since it appears that the side-effect of sexual dysfunction is dose-related in many cases it follows that a reduction in dosage or switching to an anti-psychotic that has less prolactin-raising effects would improve the situation.
At a more complex level, broaching the subject of sexual dysfunction may lead to the patient (perhaps with their partner) wishing to talk about sexual difficulties generally, their anxieties about sex and relationships, or their past experiences. It may be that mental health services need to be more sensitive and more flexible to meet this need. Initiatives such as the Access, Booking and Choice (ABC) Programme, led by NIMHE and the Modernisation Agency, are intended to support local services to meet NHS Plan delivery priorities. These include improving people’s choice and the experiences of those using services. Change can take place at a service level. At the same time, mental health nurse training and supervision may need to be enhanced in some of these areas if nurses are to feel confident and competent at helping people with this sometimes ‘forgotten’, sometimes ‘taboo’ aspect of their lives.
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Full Time: The Forgotten Taboo – antipsychotic-induced hyperprolactinaemia and its implications for mental health nursing
Authors: Shubalade Smith Is clinical senior lecturer and honorary consultant psychiatrist, the Institute of Psychiatry. Tony Gillam is clinical team leader, South Worcestershire early interventton service
MHN Vol 25 No 1 pp 6-9
Copyright Community Psychiatric Nurses Association Jan 2005
Source: Mental Health Nursing
Taken from NetDr Health News: http://www.netdr.com/news.html?id=17”