Context: Acromegaly is associated with increased morbidity and mortality. Treatment options include surgery, radiotherapy, and medical therapy.

Aims: The objective of the study was to examine the role of prolactin status, prior surgery, and radiotherapy on the response to medical therapy in patients with acromegaly and assess the relative efficacy of dopamine agonist therapy compared with somatostatin analog therapy.

Materials and Methods: A total of 276 patients with acromegaly received either dopamine agonists (DA) and/or somatostatin analogs (SSA). One hundred seventy-two patients had received surgery and 73 radiotherapy prior to receiving medical therapy. One hundred ninety-eight of 276 received DA, and 143 of 276 received SSA. GH and IGF-I values at baseline and after 12 months on therapy were analyzed.

Results: In the DA group, basal prolactin concentration did not predict response to therapy, GH percent reduction: hyperprolactinemia, 26.7% (−10.4 to 48) vs. normoprolactinemia, 34.8% (0.2–53.2), P = 0.58; IGF-I percent reduction: hyperprolactinemia 30.0% (9.2–43.1) vs. normoprolactinemia 16.8% (4–37), P = 0.45. Prior surgery was not associated with any difference in response to DA: GH percent reduction (P = 0.1) and IGF-I percent reduction (P = 0.08). By contrast, prior radiotherapy was associated with an enhanced efficacy of GH response to DA, P = 0.02. In the SSA group, there was no effect of prior surgery or radiotherapy on response of GH, but radiotherapy was associated with less marked IGF-I percent reduction (P = 0.05). SSA were more potent than DA at decreasing both GH [62.8% (20.7–85%) vs. 42.4% (−6.5 to 68.6), P < 0.008] and IGF-I [SSA 40.4% (0–64.3) vs. 8% (0–40.8), P = 0.05].

Conclusions: The effects of DA are irrespective of baseline prolactin concentrations. Prior radiotherapy is associated with differences in GH and IGF-I response to DA and SSA therapy.