What Medications Can Cause an Increase in Prolactin Levels?

Şubat 16, 2022 Yorum Gönder

Published: May 2001
ADR update

Publications

Hyperprolactinaemia With Antipsychotics

This article is more than v years old. Some content may no longer be electric current.

Prescriber Update 21: 28-32
May 2001

Medsafe Editorial Team

Dopamine acts on the pituitary every bit an inhibitor of prolactin secretion. Blockade of dopamine D2 receptors past typical antipsychotics and risperidone tin can cause hyperprolactinaemia in males and females. Other atypical antipsychotics practise non cause sustained hyperprolactinaemia because of their lower affinity for D2 receptors. Symptoms of hyperprolactinaemia include amenorrhoea, galactorrhoea, infertility, loss of libido and erectile dysfunction. Resulting hypogonadism may cause osteoporosis.

Treat symptomatic antipsychotic-induced hyperprolactinaemia past dose reduction or change to an antipsychotic with less effect on prolactin. Also consider endocrinological consultation. Warn women that menstruation and fertility will return as their prolactin levels normalise, therefore contraceptive communication may be needed.

Typical antipsychotics block dopamine inhibition of the pituitary and cause prolactin rise
Atypical antipsychotics human activity on serotonin receptors and have a lower incidence of EPS and negative symptoms
Risperidone tin cause sustained hyperprolactinaemia
Hyperprolactinaemia results in hypogonadism and may cause osteoporosis
Consider hyperprolactinaemia in a woman presenting with amenorrhoea while taking antipsychotics
Consider changing the antipsychotic in symptomatic hyperprolactinaemia
References

Prolactin is secreted by the pituitary gland. It influences gonadal function in both sexes, initiates and sustains lactation in females, and controls libido in males. Normal prolactin levels are slightly college in women than men. Physiological rises in prolactin level occur during pregnancy, reaching a maximum at the fourth dimension of delivery, falling postpartum and rising transiently with each suckling episode. Prolactin levels also rising inside an hour afterward eating and after generalised seizures.¹ To accurately measure prolactin, check serum levels fasting or at least 1 hour after food.

Typical antipsychotics cake dopamine inhibition of the pituitary and crusade prolactin rise

Secretion of prolactin by the pituitary is under inhibitory control via dopamine from the hypothalamus. Interference with dopamine secretion or action leads to an increase in serum prolactin. Some medicines can do this past blocking dopamine's action on the pituitary (e.k. phenothiazines, butyrophenones, metoclopramide, risperidone) or by depleting dopamine (east.thousand. methyldopa, reserpine).^ane Opiates tin stimulate prolactin release.² Other causes of hyperprolactinaemia include diseases of the pituitary (east.k. prolactin secreting pituitary adenomas) or hypothalamus, severe primary hypothyroidism, liver cirrhosis, terminate phase renal illness, stress, high dose oestrogens and chronic cocaine use.¹

Dopamine receptor dysfunction is thought to be function of the pathophysiology of schizophrenia.³ There are four major dopaminergic pathways (mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular) and five types of dopamine receptors (D1-v). D2 receptors are found in all the pathways.

In addition, serotonin receptors are believed to play a function in psychosis.³ Serotonin is a modulator of dopamine; if the 5HT_2A serotonin receptor is blocked, this leads to an increase in dopamine concentration. The activity of antipsychotics depends on their relative affinities for receptors of dopamine and serotonin.

Typical antipsychotics, such as haloperidol, act by blocking D2 receptors in a non-specific fashion. This results in different effects on the four dopaminergic pathways: in the limbic organization, information technology decreases positive psychotic symptoms; in the tuberoinfundibular arrangement, it causes hyperprolactinaemia; and in the nigrostriatal arrangement, it can result in extrapyramidal symptoms (EPS). The effects on the mesocortical pathway are less clear, and may be a combination of therapeutic benefits and drug-induced 'negative' symptoms.^three

Singular antipsychotics act on serotonin receptors and take a lower incidence of EPS and negative symptoms

The first available atypical antipsychotic was clozapine. Over the terminal x years it has been joined by risperidone, olanzapine and quetiapine. Atypical antipsychotics tin be defined every bit "those that are effective against psychotic symptoms with a reduced tendency to induce neurologic movement disorders".⁴ The definition may be expanded to include efficacy confronting negative symptoms and a wider spectrum of co-morbid symptoms. A prolactin-sparing effect is sometimes included in the definition, but risperidone would and then be excluded.

Singular antipsychotics accept a higher affinity for 5HT_2A compared to D2 receptors. Clozapine, olanzapine, and quetiapine also show "limbic-specific" D2 receptor bounden,ⁱⁱⁱ and hence treat psychosis with less of the negative side effects of dopamine blockade on the other dopamine pathways. Furthermore, serotonin occludent in the nigrostriatal pathways will increase dopamine and thus lower the incidence of EPS.

Risperidone can cause sustained hyperprolactinaemia

In contrast to the other atypicals, treatment with risperidone tin result in a sustained elevated prolactin level. Information technology causes a rapid⁵, dose-dependent ascent in prolactin³ like to that observed with haloperidol.⁶ Yet, an assay of randomised double-bullheaded studies of risperidone found the level of prolactin did not correlate with the incidence of clinically detected prolactin-related adverse effects in either sexual activity at usual doses.half-dozen Sustained hyperprolactinaemia is less frequent with the other atypicals. Although olanzapine causes an early dose-related ascension in prolactin, this is less frequent and less marked than that seen with haloperidol, and is ordinarily transient.⁷ A ascension in prolactin is seen in about one-half of patients on olanzapine compared to over 90% of those taking risperidone, and enduring increases were less frequent in those taking olanzapine.⁸

Why the difference? Risperidone has a high affinity for D2 every bit well as serotonin receptors.³ Information technology is not "limbic specific" for the mesolimbic over the nigrostriatal tract like the other atypicals.^ix Risperidone antagonises dopamine in the tuberoinfundibular organisation causing a ascent in prolactin. All the same, its antagonist action at 5HT,sub>2A receptors in the nigrostriatal pathways may partially explain why risperidone has a low propensity to cause EPS despite its blockade of D2 receptors.

Hyperprolactinaemia results in hypogonadism and may cause osteoporosis

Hyperprolactinaemia is associated with hypogonadism due to inhibition of hypothalamic release of LHRH. The resulting low levels of oestrogen and testosterone may take long-term consequences. Some advocate screening for hyperprolactinaemia in all antipsychotic treated patients.

In premenopausal women, high prolactin will lower oestrogen levels. This may contribute to the development of reduced os mineral density, although a causal clan between antipsychotics and osteoporosis has not been established.¹⁰ Menopausal women may need to exist assessed for hormone replacement therapy (HRT), however this will need to be weighed upwardly against the risks of HRT, such as venous thromboembolism in a group among whom smoking and obesity are common. Loftier prolactin may also cause male hypogonadism through lowering of testosterone levels. Testosterone in men is important for improving lean trunk mass and reducing fat mass.^vi When prescribing antipsychotics, consider the significance of other risk factors for osteoporosis such as age, menopause, glucocorticoid use, hyperthyroidism, calcium imbalance, polydipsia, alcoholism, smoking, amenorrhoea, anorexia nervosa, use of medicines such every bit lithium, dietary deficiency, lack of sunday, and immobility.^eleven

At that place has also been business organisation regarding hyperprolactinaemia and an increased risk of chest cancer. Although there is evidence in in vitro and fauna studies, in that location are no supporting human data.^{half dozen,9}

Consider hyperprolactinaemia in a adult female presenting with amenorrhoea while taking antipsychotics

In whatever woman presenting with secondary amenorrhoea on antipsychotics, hyperprolactinaemia must be considered in the differential diagnosis (think to exclude pregnancy). Women with hyperprolactinaemia may present with irregular menses, galactorrhoea, decreased libido and even infertility despite regular menstruation. Men may present with reduction in libido, impotence, infertility, and rarely galactorrhoea and gynaecomastia. Other causes of hyperprolactinaemia should be investigated if the prolactin level is raised. The patient should be examined for chest wall irritation (which can promote galactorrhoea and raise prolactin), signs of a sellar mass (including assessment of visual fields), and blood tests washed for TSH¹² (exclude hypothyroidism) and creatinine (exclude renal failure as a cause of hyperprolactinaemia). Referral for CT or MRI or an endocrinology consultation may be considered.

Consider changing the antipsychotic in symptomatic hyperprolactinaemia

Handling of symptomatic hyperprolactinaemia in a patient on antipsychotics firstly involves exclusion of other aetiologies, followed by consideration of a change of medication to a prolactin-sparing antipsychotic or reduction in dose if the patient's mental state is stable. If this proves difficult, then an endocrinologist should be consulted and the risks and benefits of hormone replacement considered. Monitoring the patient's psychiatric status closely is essential if changing regimens. Asymptomatic hyperprolactinaemia in itself should not be an indication for changes to medication.

For all treatment changes, women must exist warned that period may resume along with fertility. Contraceptive advice may demand to exist given. With the resumption of normal cycles, there is also the risk that premenstrual exacerbation of schizophrenic symptoms may occur, requiring doses of antipsychotics to exist adjusted over the bicycle.

In club to adequately monitor for hyperprolactinaemia, a menstrual history should be taken prior to commencing a premenopausal woman on antipsychotics. When choosing an antipsychotic, it is of import to weigh the overall risks and benefits for the private patient (male or female). The atypical antipsychotics, while having a better side effect profile than the older agents, still carry a pregnant burden of handling which varies betwixt the atypicals. Attending has been drawn to some of these in recent Prescriber Update articles.^13,xiv

References

Wilson JD. Endocrinology. In Fauci Every bit, Martin JB, Braunwald East et al (Eds) Harrison'southward Principles of Internal Medicine. 14th edition. 1998: International Edition, McGraw-Loma Inc.
Petty RG. Prolactin and antipsychotic medications: mechanism of activity. Schizophrenia Enquiry 1999;35:S67-S73.
Worrel JA, Marken PA, Beckman SE, Ruehter VL. Atypical antipsychotic agents: a critical review. Am J Wellness-syst Pharm 2000;57:238-255.
Dickson RA, Seeman MV, Corenblum B. Hormonal side effects in women: typical versus atypical antipsychotic treatment. J Clin Psychiatry 2000;61(suppl 3):10-15.
Huang M-50, Van Peer A, Woestenborghs R et al. Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin Pharmacol Ther 1993;54(3):257-268.
Kleinberg DL, Davis JM, De Coster R et al. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacology 1999;19(1):57-61.
Crawford AMK, Beasley CM, Tollefson GD. The astute and long-term issue of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophrenia Enquiry 1997;26:41-54.
Tran PV, Hamilton SH, Kuntz AJ et al. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacology 1997;17(5):407-418.
Popli A, Gupta S, Rangwani SR. Risperidone-induced galactorrhea associated with a prolactin elevation. Ann Clin Psychiatry 1998;ten(1):31-33.
Hamner MB, Arana GW. Hyperprolactinaemia in antipsychotic-treated patients. Guidelines for abstention and direction. CNS Drugs 1998; 10(three):209-222.
Halbreich U, Palter South. Accelerated osteoporosis in psychiatric patients: possible pathophysiological processes. Schizophrenic Bulletin 1996;22(three):447-454.
Spitzer Thousand, Sajjad R, Benjamin F. Pattern of evolution of hyperprolactinemia afterward initiation of haloperidol therapy. Obstetrics & Gynaecology 1998;91(five):693-695.
Medsafe Editorial Squad. Clozapine and Hyperglycaemia. Prescriber Update June 1999;18:36-38.
Medsafe Editorial Team. Potentially fatal complications of clozapine therapy: myocarditis, venous thromboembolism and constipation. Prescriber Update February 2001;20:14-18.