The Novel Use of Very High Doses of Cabergoline and a Combination of Testosterone and an Aromatase Inhibitor in the Treatment of a Giant Prolactinoma

Gillam, Mary P.; Middler, Stewart A.; Freed, Daniel J.; Molitch, Mark E.

doi:10.1210/jc.2002-020426

Cited by 87 publications

(57 citation statements)

References 23 publications

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“…In this patient, the administration of the nonaromatizable androgen, stanozolol, also was associated with a rise in PRL levels [52]. In the second case, a rise in PRL levels was also associated with testosterone administration but the rise was blocked when the aromatase inhibitor, anastrazole was added to block estrogen formation [53].…”

Section: Late Development Of Dopamine Agonist Resistancementioning

confidence: 71%

Pharmacologic Resistance in Prolactinoma Patients

2005

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Pharmacologic resistance to dopamine agonists is defined here as failure to normalize PRL levels and failure to decrease macroprolactinoma size by >or=50%. Failure to normalize PRL levels is found in about one-quarter of patients treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. Failure to achieve at least a 50% reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. The cause of dopamine resistance is primarily a decrease in D(2) receptors but the receptors have normal affinity for dopamine. Treatment approaches for patients resistant to dopamine agonists include changing to another dopamine agonist and increasing the dose of the drug as long as there is continued response to the dose increases and no adverse effects with higher doses. Transsphenoidal surgery is also an option. Clomiphene, gonadotropins, and GnRH can be used if fertility is desired. For those not desiring fertility, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. In many patients modest or even no reduction in tumor size may be acceptable as long as there is not tumor growth. Hormone replacement (estrogen or testosterone) may cause a decrease in efficacy of the dopamine agonist so that it must be carried out cautiously. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches.

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Section: Late Development Of Dopamine Agonist Resistancementioning

confidence: 71%

Pharmacologic Resistance in Prolactinoma Patients

2005

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“…Estrogen appears therefore to differentially effect cell proliferation and PRL secretion (30). Two case reports of male patients with macroprolactinomas treated with cabergoline demonstrated an increase in the PRL level following testosterone supplementation, which was reversed by the aromatase inhibitor anastrozole (23,31). This was considered a demonstration of the negative impact of estrogens on PRL tumors, and yet there was no mention of any tumor growth.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth

Delgrange

Vasiljevic

Wierinckx

et al. 2015

European Journal of Endocrinology

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Context: A sex difference in the progression of prolactin (PRL) tumors has been disputed for years. Objective: To compare tumor characteristics and postoperative clinical course between men and women, and correlate data with estrogen receptor alpha (ERa (ESR1)) expression status. Design, patients, and methods: Eighty-nine patients (59 women and 30 men) operated on for a prolactinoma and followed for at least 5 years were selected. Tumors were classified into five grades according to their size, invasion, and proliferation characteristics. The ERa expression was detected by immunohistochemistry and a score (0-12) calculated as the product of the percentage of positive nuclei and the staining intensity. Results: We found a significant preponderance of high-grade tumors among men and a lower surgical cure rate in men (23%) than in women (71%). Patients resistant to medical treatment were mainly men (7/8), six of whom showed tumor progression despite postoperative medical treatment, which led to multiple therapies and eventually death in three. The median score for ERa expression was 1 in men (range, 0-8) and 8 in women (range, 0-12) (P!0.0001). The expression of ERa was inversely correlated with tumor size (rZK0.59; P!0.0001) and proliferative activity. All dopamine agonist-resistant tumors and all grade 2b (invasive and proliferative) tumors (from ten men and four women) were characterized by low ERa expression. Conclusions: PRL tumors in men are characterized by lower ERa expression, which is related to higher tumor grades, resistance to treatment, and an overall worse prognosis. IntroductionPhenotypically, prolactin (PRL)-secreting pituitary tumors vary greatly, ranging from small indolent tumors to large invasive ones. Sex is a widely accepted factor influencing tumor size (1). The larger size of PRL tumors (prolactinoma) in men is often attributed to differences in detection, with diagnostic delays being the cause of more advanced PRL tumors in men (2). Nevertheless, young men usually present with large PRL tumors and most women of childbearing age with intrasellar tumors, even after a long duration of symptoms (3). When considering giant PRL tumors, the median age at diagnosis is almost 10 years lower in men than in women (4). PRL tumors in men are also less sensitive to dopamine agonists (DAs) (3) and often highly vascularized, whereas in women,

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“…Medical treatment with dopamine agonists (DA) corrects hyperprolactinemia, decreases tumor size, and restores gonadal function in most patients (1). However, 30-50% of male patients with prolactinomas under DA treatment, both with normal and with high prolactin levels, still remain hypogonadal (2)(3)(4)(5)(6)(7). Persistent hypogonadism in these patients is treated with testosterone replacement, most often with intramuscular injections that require frequent applications and induce large fluctuations in serum testosterone levels with corresponding fluctuations in patients' energy, libido, sexual performance, and mood (8,9).…”

Section: Introductionmentioning

confidence: 99%

Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment

Ribeiro

Abucham

2009

European Journal of Endocrinology

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Context: Persistence of hypogonadism is common in male patients with prolactinomas under dopamine agonist (DA) treatment. Conventional therapy with testosterone causes undesirable fluctuations in serum testosterone levels and inhibition of spermatogenesis. Objective: To evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas. Design: Open label, single-arm, prospective trial. Patients: Fourteen adult hypogonadal males (testosterone !300 ng/dl and low/normal LH) with prolactinomas on DA, including seven with high prolactin (range: 29-1255 mg/l; median: 101 mg/l) despite maximal doses of DA. Intervention: Clomiphene (50 mg/day orally) for 12 weeks. Measures: Testosterone, estradiol, LH, FSH, and prolactin were measured before and 10 days, 4, 8, and 12 weeks after clomiphene. Erectile function, sperm analysis, body composition, and metabolic profiles were evaluated before and after clomiphene. Results: Ten patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone O300 ng/dl). Testosterone levels increased from 201G22 to 457 G37 ng/dl, 436G52, and 440G47 ng/dl at 4, 8, and 12 weeks respectively (0.001!P!0.01). Estradiol increased significantly and peaked at 12 weeks. LH increased from 1.7G0.4 to 6.2G2.0 IU/l, 4.5G0.7, and 4.6G0.7 IU/l at 4, 8, and 12 weeks respectively (0.001!P!0.05). FSH levels increased in a similar fashion. Prolactin levels remained unchanged. Erectile function improved (P!0.05) and sperm motility increased (P!0.05) in all six patients with asthenospermia before clomiphene. Conclusions: Clomiphene restores normal testosterone levels and improves sperm motility in most male patients with prolactinomas and persistent hypogonadism under DA therapy. Recovery of gonadal function by clomiphene is independent of prolactin levels.

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The Novel Use of Very High Doses of Cabergoline and a Combination of Testosterone and an Aromatase Inhibitor in the Treatment of a Giant Prolactinoma

Cited by 87 publications

References 23 publications

Pharmacologic Resistance in Prolactinoma Patients

Pharmacologic Resistance in Prolactinoma Patients

Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth

Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment

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