Anastrozole as add-on therapy for cabergoline-resistant prolactin-secreting pituitary adenomas: real-life experience in male patients

Ceccato, Filippo; Lizzul, Laura; Voltan, Giacomo; Barbot, Mattia; Scaroni, Carla

doi:10.1007/s11102-021-01165-0

Cited by 11 publications

(9 citation statements)

References 48 publications

(60 reference statements)

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“…References from the manual search were all included in the electronic database searches. We reviewed 10 full-text papers for eligibility, and 6 studies published between 2002 and 2021 met the inclusion criteria and were included in the systematic review [ 17 , 18 , 19 , 20 , 21 , 22 ]. A summary of the trials included in the systematic review is shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…A summary of the trials included in the systematic review is shown in Table 1 . Of the included studies, five were case reports, each reporting on a single case [ 17 , 18 , 19 , 20 , 22 ], and one study was a case series reporting on four patients [ 21 ]. Anastrozole was the aromatase inhibitor used in four of the studies [ 18 , 19 , 21 , 22 ], while letrozole was used in two cases [ 17 , 20 ] ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…At 1 year, the mean decline in prolactin secretion was 70% (ranging from −44% to −97%), and one patient achieved normal prolactin levels. The mean tumor volume shrinkage was 47% (ranging from −25% to −69%) [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

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The Role of Aromatase Inhibitors in Male Prolactinoma

Akirov

Rudman

2023

JCM

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Background: dopamine agonists are the recommended treatment for male prolactinomas, but some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to persistent hypogonadism that requires treatment with testosterone. However, testosterone replacement therapy may be associated with a decrease in the efficacy of dopamine agonists due to the aromatization of testosterone to estradiol, which can stimulate the proliferation and hyperplasia of lactotroph cells in the pituitary, inducing resistance to dopamine agonists. Objective: this paper systematically reviewed the role of aromatase inhibitors for men with prolactinoma and dopamine-agonist-resistant or persistent hypogonadism following treatment. Method: we performed a systematic review of all studies (according to PRISMA guidelines), assessing the role of aromatase inhibitors, including anastrozole and letrozole, for male prolactinoma. An English-language search for relevant studies was conducted on PubMed from its inception to 1 December 2022. The reference lists of the relevant studies were also reviewed. Results: our systematic review identified six articles (nine patients), including five case reports and a single case series, on the use of aromatase inhibitors for male prolactinomas. Reducing estrogen levels with an aromatase inhibitor improved sensitivity to dopamine agonists, as the addition of anastrozole or letrozole improves the control of prolactin levels and may lead to the shrinkage of tumors. Conclusion: aromatase inhibitors are of potential value to patients with dopamine-agonist-resistant prolactinoma, or when hypogonadism persists while using high-dose dopamine agonists.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Role of Aromatase Inhibitors in Male Prolactinoma

Akirov

Rudman

2023

JCM

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“…It has been related with aggressive behavior and invasiveness of adenomas in both men and post-menopausal women 58 , 59 . Anastrozole, an aromatase inhibitor, has been added in the therapeutic regimen of four male patients with cabergoline-resistant prolactinomas and prolactin levels decreased (in one case it normalized) while the tumor size decreased by approximately 47% (mean reduction) without serious adverse events 60 .…”

Section: Prolactinοmasmentioning

confidence: 99%

Recent advances in understanding and managing pituitary adenomas

Markou¹,

Lavrentaki²,

Ntali³

2023

Fac Rev

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Pituitary adenomas (PAs) are common intracranial tumors. Despite their benign nature, PAs may cause a significant burden of disease, leading to either hormonal disturbances or local compression. A subset of PAs presents an aggressive behavior that remains difficult to predict, and in rare cases they metastasize. Therefore, early diagnosis and treatment are important. Advances in molecular pathology have improved the understanding of their pathogenesis and offer opportunities to identify and target novel pathways. Improved imaging and functional molecular techniques precisely detect even very small tumors and guide targeted treatment. Transsphenoidal surgery is the first-line treatment for the majority of PAs, and advances in the field of endoscopic neurosurgery offer excellent outcomes. Dopamine agonists (DAs) are traditionally the first-line treatment for prolactinomas. For patients with acromegaly, first- and second-generation somatostatin analogues (SSAs) are applied when surgery is not successful or not indicated. For Cushing’s disease (CD), drugs targeting adrenal steroidogenesis, somatostatin receptors in the pituitary, and glucocorticoid receptors are used to treat hypercortisolism in patients with persistent or recurrent CD, for those who are not good surgical candidates, and as a bridge treatment for those who have undergone radiation treatment until cortisol levels are controlled. Temozolomide (TMZ) is the first-line chemotherapy for aggressive PAs, but new experimental therapies, like the anti-vascular endothelial growth factor (anti-VEGF) therapy, mechanistic target of rapamycin (mTOR) inhibitors, tyrosine kinase inhibitors, and cell cycle and checkpoint inhibitors, are now available. Radiotherapy is offered to patients with residual, recurrent, or progressive tumors. Modern techniques in radiotherapy planning and delivery are able to deliver high doses to the target tissue while sparing vital structures. As we familiarize ourselves with the biological behavior of PAs and our therapeutic armamentarium expands, the next goal is to tailor and personalize treatment to each individual patient so as to achieve the best outcome.

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“…An important role might also be played, especially in males, by the intra-tumoral activity of aromatase, which locally transforms testosterone into estradiol [ 90 ]. Recently, we used anastrozole (an aromatase-inhibitor) to treat four male patients harboring macro-prolactinomas resistant to Cabergoline: a reduction of prolactin levels and a significant shrinkage of the adenomas was observed in all cases [ 91 ]. However, despite the fact that aromatase expression was proved in GH-secreting pituitary cells [ 57 ], a therapeutic approach with aromatase inhibitors has never been investigated in acromegalic patients.…”

Section: Clinical Use Of Estrogens And/or Serms In Patients With Acro...mentioning

confidence: 99%

Role of Estrogen and Estrogen Receptor in GH-Secreting Adenomas

Voltan

Mazzeo

Regazzo

et al. 2023

IJMS

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Acromegaly is a rare disease with several systemic complications that may lead to increased overall morbidity and mortality. Despite several available treatments, ranging from transsphenoidal resection of GH-producing adenomas to different medical therapies, complete hormonal control is not achieved in some cases. Some decades ago, estrogens were first used to treat acromegaly, resulting in a significant decrease in IGF1 levels. However, due to the consequent side effects of the high dose utilized, this treatment was later abandoned. The evidence that estrogens are able to blunt GH activity also derives from the evidence that women with GH deficiency taking oral estro-progestins pills need higher doses of GH replacement therapy. In recent years, the role of estrogens and Selective Estrogens Receptor Modulators (SERMs) in acromegaly treatment has been re-evaluated, especially considering poor control of the disease under first- and second-line medical treatment. In this review, we analyze the state of the art concerning the impact of estrogen and SERMs on the GH/IGF1 axis, focusing on molecular pathways and the possible implications for acromegaly treatment.

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Anastrozole as add-on therapy for cabergoline-resistant prolactin-secreting pituitary adenomas: real-life experience in male patients

Cited by 11 publications

References 48 publications

The Role of Aromatase Inhibitors in Male Prolactinoma

The Role of Aromatase Inhibitors in Male Prolactinoma

Recent advances in understanding and managing pituitary adenomas

Role of Estrogen and Estrogen Receptor in GH-Secreting Adenomas

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