{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:06:37Z","timestamp":1791875197164,"version":"4.3.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Mereo BioPharma 2 Limited"},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mereo BioPharma 2 Limited"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Assessment of the efficacy and safety\/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Placebo-controlled, double-blind, RCT, in 70 sites in Europe\/USA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patient inclusion criteria: men with BMI of 30-50\u2005kg\/m2, morning total testosterone (TT) &amp;lt; 10.41\u2005nmol\/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1\/0.3\/1.0\u2005mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in \u226575% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH\/FSH. Safety was assessed through adverse events and laboratory monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusions<\/jats:title>\n                    <jats:p>Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1\u2005kg\/m2 and TT 7.97\u2005nmol\/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35\u2005nmol\/L, for leflutrozole 0.1\u2005mg, 0.3\u2005mg, and 1.0\u2005mg groups respectively, vs 8.04\u2005nmol\/L for placebo. LH\/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume\/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean \u22121.24%, \u22121.30%, \u22122.09%) and 0.66% for 0.1\u2005mg, 0.3\u2005mg, 1.0\u2005mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH\/LH and semen parameter changes support that leflutrozole may preserve\/improve testicular function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration number<\/jats:title>\n                    <jats:p>NCT02730169.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvad099","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T14:21:46Z","timestamp":1692022906000},"page":"297-308","source":"Crossref","is-referenced-by-count":24,"title":["Leflutrozole in male obesity-associated hypogonadotropic hypogonadism: Ph 2b double-blind randomised controlled trial"],"prefix":"10.1093","volume":"189","author":[{"given":"T Hugh","family":"Jones","sequence":"first","affiliation":[{"name":"Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Trust , Barnsley , United Kingdom"},{"name":"Department of Oncology and Metabolism, University of Sheffield Medical 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