Antipsychotic-induced hyperprolactinaemia, hypogonadism and osteoporosis in the treatment of schizophrenia
Abstract
Treatment of schizophrenic illness usually involves the long-term administration of antipsychotic drugs. Most antipsychotic agents antagonise the actions of endogenous dopamine (DA) at DA-2 receptors in the brain. The relative affinity for, and binding time to, DA-2 receptors was considered to be one of the key determinants of the antipsychotic potency of classical antipsychotic drugs. Some newer atypical antipsychotics, of which clozapine is the prototype, have a relatively poor affinity for DA-2 receptors; whereas other atypical antipsychotics are potent DA-2 antagonists. The propensity of antipsychotic agents to cause hyperprolactinaemia is related to their potency in antagonising DA-2 receptors on the anterior pituitary. In our studies, bone loss was consistently related to DA-2 antagonist potency of antipsychotic drugs, rather than their classification using conventional `typical' versus `atypical' systems. It is established that hyperprolactinaemia causes suppression of the reproductive endocrine axis and consequent bone mineral density (BMD) loss. Results from our group and others have demonstrated that a similar pathophysiological process is occurring in individuals with antipsychotic-induced hyperprolactinaemia. We found high rates of osteoporosis and osteopenia in those taking long-term antipsychotic drugs, and this was related to the dose and duration of treatment. Bone loss was associated with hypogonadism in male and female groups. Young Caucasian women appear to be particularly vulnerable to developing hyperprolactinaemia and the associated hypogonadism and bone loss. The occurrence of menstrual dysfunction should alert clinical suspicions of hyperprolactinaemia and bone de-mineralisation. Lastly, there are no published trials examining the effects of hormone replacement on BMD in those taking long-term antipsychotic drugs, but preliminary findings from our studies suggest that active management of bone loss in those with antipsychotic-associated bone disease may halt or even reverse this process.
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The available data seem to indicate that hyperprolactinemia with associated hypogonadism may be a risk factor, leading to bone mineral loss in women as well as men.
“Nevertheless, the available data seem to indicate that hyperprolactinemia with associated hypogonadism may be a risk factor (488), leading to bone mineral loss in women as well as men (499).”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [499]
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- Authors
- O'Keane, V.
- Affiliations
- Department of Psychiatry, Institute of Psychiatry, De Crespigny Park, London, UK, v.o'keane@iop.kcl.ac.uk
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2008-03
- Volume
- 22
- Issue
- 2_suppl
- Pages
- 70-75
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2164853579
- Cited by
- 126
- References
- 27
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 10 · 2012: 10
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- hypogonadism, osteoporosis, schizophrenia, atypical antipsychotics, clozapine, dopamine D2 receptor antagonism, bone mineral loss, menstrual disorders, hormone replacement therapy, long-term antipsychotic treatment
- MeSH terms
- Female, Humans, Hyperprolactinemia, Hypogonadism, Male, Osteoporosis, Pituitary Gland, Prolactin, Receptors, Dopamine, Schizophrenia, Antipsychotic Agents, Bone Density, Dopamine Antagonists
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