A Meta-Analysis of the Prevalence of Cardiac Valvulopathy in Patients With Hyperprolactinemia Treated With Cabergoline

Stiles, Craig E; Tetteh-Wayoe, Eugene T; Bestwick, Jonathan P.; Steeds, Richard P.; Drake, William

doi:10.1210/jc.2018-01071

Cited by 45 publications

(42 citation statements)

References 26 publications

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“…Common side effects of DAs include nausea and/or vomiting and postural hypotension which can lead to dizziness and syncope, a digital Raynaud-type syndrome, and, more rarely, leg cramps, flushing, and nasal congestion [94]. High dose DA (as offered in Parkinson's syndrome) increases the risk of cardiac valvulopathy [95] but the risk of clinically significant valvulopathy in patients with prolactinoma is still not clearly established [96]. Most studies on prolactinoma patients do not show an elevated risk [97][98][99] but, given the uncertainty around the risk of valvulopathy in this setting, current guidelines recommend screening echocardiography prior to initiating DA, and thereafter every five years for patients taking cabergoline less than 2 mg per week or annually for those on more than 2 mg per week [100].…”

Section: Dopamine Agonistsmentioning

confidence: 99%

Hyperprolactinaemia

Samperi

Lithgow

Karavitaki

2019

JCM

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Hyperprolactinaemia is one of the most common problems in clinical endocrinology. It relates with various aetiologies (physiological, pharmacological, pathological), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be taken into account when interpreting the prolactin values. Medications and sellar/parasellar masses (prolactin secreting or acting through "stalk effect") are the most common causes of pathological hyperprolactinaemia. Hypogonadism and galactorrhoea are well-recognized manifestations of prolactin excess, although its implications on bone health, metabolism and immune system are also expanding. Treatment mainly aims at restoration and maintenance of normal gonadal function/fertility, and prevention of osteoporosis; further specific management strategies depend on the underlying cause. In this review, we provide an update on the diagnostic and management approaches for the patient with hyperprolactinaemia and on the current data looking at the impact of high prolactin on metabolism, cardiovascular and immune systems.

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Section: Dopamine Agonistsmentioning

confidence: 99%

Hyperprolactinaemia

Samperi

Lithgow

Karavitaki

2019

JCM

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“…Although side effects of cabergoline were recorded in 68% of women in a large cohort with hyperprolactinemic amenorrhea, only 3% of them ultimately had to discontinue drug therapy due to intolerance. [16] Also, cabergoline-associated valvulopathy is uncommon, [17,18] and its clinical significance remains unclear [19]. In a recent cohort study, no association was reported between a clinically significant valvulopathy and low-dose cabergoline therapy [20].…”

Section: Introductionmentioning

confidence: 99%

First-line surgery in prolactinomas: lessons from a long-term follow-up study in a tertiary referral center

Andereggen

Frey

Andres

et al. 2021

J Endocrinol Invest

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Context Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1). Methodology Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients’ dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed. Results A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4–37.7, p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs. Conclusions First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.

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“…Interestingly, however, we found that a median cumulative exposure of only > 115 mg cabergoline over a relatively modest exposure time (median 2.8-3.2 years) was associated with higher agesex-adjusted odds of primarily mild valvular regurgitation involving two or more valves compared with receiving only bromocriptine. Other studies in patients with hyperprolactinemia have found either no association of dopamine agonists with valvular abnormalities [5, 8-12, 26, 27] or a higher prevalence of regurgitation, generally involving the tricuspid valve, [5,[13][14][15][16][17][18] with no relation to the dose, duration of treatment, or cumulative dose [9,24,28]. Other studies have reported an association between long-term cabergoline exposure and aortic valve calcification in this population [29,30].…”

Section: Discussionmentioning

confidence: 79%

“…Whether the risk is similar in conditions where lower doses of cabergoline are prescribed is still not well understood, with conflicting results in published studies [5,[8][9][10][11][12][13][14][15][16][17]. A recent meta-analysis of 13 casecontrol studies comparing patients treated with cabergoline for at least 6 months for hyperprolactinemia versus controls matched for selected patient characteristics reported higher odds of any tricuspid regurgitation but no other significant differences in other valves [18]. However, no included study in the meta-analysis had more than 102 patients treated with cabergoline, several studies examined only shorter-term cabergoline exposure, there was a wide range of cumulative cabergoline dosage across studies, and not all studies included blinded, standardized evaluations of echocardiograms [18].…”

Section: Introductionmentioning

confidence: 99%

Cardiac valvular abnormalities associated with use and cumulative exposure of cabergoline for hyperprolactinemia: the CATCH study

Budayr

Tan

et al. 2020

BMC Endocr Disord

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Background: Whether lower dose cabergoline therapy for hyperprolactinemia increases risk of valvular dysfunction remains controversial. We examined valvular abnormalities among asymptomatic adults with hyperprolactinemia treated with dopamine agonists. Methods: This cross-sectional study was conducted among adults receiving cabergoline or bromocriptine for > 12 months for hyperprolactinemia and had no cardiac-related symptoms. Cardiac valve morphology and function were assessed from transthoracic echocardiograms at the study visit (except for two participants) with evaluation performed blinded to type and duration of dopamine agonist received. Results: Among 174 participants (mean age 49 ± 13 years, 63% women) without known structural heart disease before starting therapy, 62 received only cabergoline, 63 received only bromocriptine, and 49 received both. Median cabergoline use was 2.8 years in cabergoline only users and 3.2 years for those exposed to both cabergoline and bromocriptine; median bromocriptine use was 5.5 years in bromocriptine only users and 1.1 years for those exposed to both cabergoline and bromocriptine. Compared with bromocriptine only users (17.5%), regurgitation of ≥1 valve was more common for cabergoline only (37.1%, P = 0.02) but not for combined exposure (26.5%, P = 0.26). Compared with bromocriptine only exposure (1.6%), regurgitation of ≥2 valves was more common for cabergoline only (11.3%, P = 0.03) and combined exposure (12.2%, P = 0.04). Cabergoline only users had higher age-sex-adjusted odds for ≥1 valve with grade 2+ regurgitation compared to bromocriptine only users (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI]:1.3-7.5, P = 0.008), but the association for combined exposure to cabergoline and bromocriptine was not significant (aOR 1.7, 95%CI:0.7-4.3, P = 0.26). Compared to bromocriptine only, age-sex-adjusted odds of ≥2 valves with grade 2+ regurgitation were higher for both cabergoline only (aOR 8.4, 95% CI:1.0-72.2, P = 0.05) and combined exposure (aOR 8.8, 95% CI:1.0-75.8, P = 0.05). Cumulative cabergoline exposure > 115 mg was associated with a higher age-sex adjusted odds of ≥2 valves with grade 2+ regurgitation (aOR 9.6, 95%CI:1.1-81.3, P = 0.04) compared to bromocriptine only.

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A Meta-Analysis of the Prevalence of Cardiac Valvulopathy in Patients With Hyperprolactinemia Treated With Cabergoline

Abstract: Treatment with low dose cabergoline in hyperprolactinemia appears to be associated with an increased prevalence of tricuspid regurgitation. The clinical significance of this is unclear and requires further investigation. 51.

Cited by 45 publications

References 26 publications

Hyperprolactinaemia

Hyperprolactinaemia

First-line surgery in prolactinomas: lessons from a long-term follow-up study in a tertiary referral center

Cardiac valvular abnormalities associated with use and cumulative exposure of cabergoline for hyperprolactinemia: the CATCH study

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