Effect of gender and gonadal status on the long-term response to somatostatin analogue treatment in acromegaly

Background: GH and IGF-I secretion is related to gender and age. Objective: To evaluate the impact of gender and gonadal status on the long-term sensitivity to the somatostatin analogues depot octreotide long-acting release (OCT-LAR) and lanreotide (LAN). Patients: Seventy-three patients with active acromegaly (37 women, median age 34 years; 36 men, median age 38 years) who had not previously been treated with somatostatin analogues were studied: 24 women and 23 men were newly diagnosed; 22 men (61.1%) and 17 women (45.9%) had hypogonadism (P = 0.28). Exclusion criteria were age > 45 years, follow-up less than 12 months, mixed GH/PRL-secreting adenomas. Study design: Observational, analytical, retrospective. Outcome measures: (1) Disease control measured as serum GH <2.5 μg/l and IGF-I normal for age and gender; (2) reduction in tumour volume graded as absent (<25%), mild (25-50%) and notable (> 50%). Results: Basal GH, but not IGF-I, levels were higher in women than in men both in the entire series and in 'de novo' patients (97.8 ± 42.2 vs. 71.1 ± 32.6 μg/l, P = 0.021). After 12 and 24 months of treatment, respectively, disease control was achieved similarly in men (57.1 and 86.7%) and women (48.6 and 86.7%). Hypogonadal men had longer disease duration than eugonadal men (P = 0.022), without any difference in the other parameters. No difference was found between eugonadal and hypogonadal women. Eugonadal men had a smaller tumour volume at baseline than eugonadal women (1396 ± 794 vs. 2896 ± 2871 mm³, P = 0.025). In men undergoing testosterone replacement and withdrawal, there was no change in GH and IGF-I levels after 12 and 24 months of treatment with either LAR or LAN. In the seven women receiving oestro-progestinic replacement, after 24 months of LAR or LAN treatment GH levels were higher during replacement than at withdrawal and IGF-I levels were lower during replacement than withdrawal. Tumour volume decreased significantly in both women and men without any difference between them: the percentage tumour shrinkage in men and women was similar either after 12 (34.4 ± 24.4 vs. 40.7 ± 22.5%, P = 0.38) or 24 months of treatment (58.5 ± 17.4 vs. 56.1 ± 23.6%, P = 0.75). Similarly, there was no difference in tumour volume between hypogonadal and eugonadal women and men. Conclusions: The results of this study demonstrate that long-term responsiveness to OCT-LAR is similar in women and men. Care should be taken in women with acromegaly and hypogonadism treated with somatostatin analogues and oral oestro-progestinic as in this case GH levels are higher while IGF-I levels are lower than after the somatostatin analogues alone.