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


METHODS
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 microg/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 microg/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 mm(3), 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.
Colao
Annamaria
A
Departments of Molecular and Clinical Endocrinology and Oncology, 'Federico II' University of Naples, Naples, Italy. colao@unina.it
Pivonello
Rosario
R
Cappabianca
Paolo
P
Briganti
Francesco
F
Tortora
Fabio
F
Auriemma
Renata S
RS
De Martino
Maria Cristina
MC
Marzullo
Paolo
P
Lombardi
Gaetano
G
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D012737:Sex Factors; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide