Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats.
High-dose testosterone enanthate (TE) may prevent hypogonadism-induced osteopenia. For this study, 3-mo-old male and female Fisher SAS rats underwent sham surgery, gonadectomy (GX), or GX plus 28 days TE administration (7.0 mg/wk). GX reduced serum sex hormones (i.e., testosterone, dihydrotestosterone, and estradiol) (P < 0.05) in both sexes and bone concentrations of testosterone (males only), and estradiol (females only). GX also elevated urine deoxypyridinoline/creatinine in both sexes and serum osteocalcin (females only), findings that are consistent with high-turnover osteopenia. GX reduced cancellous bone volume (CBV) and increased osteoid surfaces in tibia of both sexes. GX males also experienced reduced trabecular number and width and increased trabecular separation, whereas GX females experienced increased osteoblast and osteoid surfaces. Bone biomechanical characteristics remained unaffected by GX, except that femoral stiffness was reduced in females. In contrast, TE administration to GX rats elevated serum and bone androgens to supraphysiological concentrations in both sexes but altered neither serum nor bone estradiol in males. Additionally, TE did not prevent GX-induced reductions in serum or bone estradiol in females. TE also reduced markers of high-turnover osteopenia in both sexes. In males, TE prevented GX-induced changes in trabecular number and separation, CBV, and osteoid surfaces while diminishing osteoblast and osteoclast surfaces; however, these changes were not fully prevented in females. In both sexes, TE increased femoral length and femoral maximal strength to above that of Sham and GX animals while preventing the loss of femoral stiffness in females. In conclusion, TE administration appears protective of cancellous bone in male rats and augments cortical bone strength in both sexes.
Yarrow
Joshua F
JF
Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Gainesville, Florida, USA.
Conover
Christine F
CF
Purandare
Amol V
AV
Bhakta
Ashish M
AM
Zheng
Naiquan
N
Conrad
Bryan
B
Altman
Molly K
MK
Franz
Sarah E
SE
Wronski
Thomas J
TJ
Borst
Stephen E
SE
D000596:Amino Acids / Q000652:urine; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D013196:Dihydrotestosterone / Q000097:blood / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D013718:Tensile Strength / Q000187:drug effects; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D000728:Androgens; D013196:Dihydrotestosterone; D015675:Osteocalcin; D013739:Testosterone; D004958:Estradiol; C004648:testosterone enanthate; C036020:deoxypyridinoline; D003404:Creatinine