4379
document
Sublingual administration of micronized estradiol and progesterone , with and without micronized testosterone : effect on biochemical markers of bone metabolism and bone mineral density . OBJECTIVES The purpose of this investigation was to evaluate the relative efficacy of the sublingual administration of micronized estradiol ( E2 ) , progesterone ( P4 ) , and testosterone ( T ) on bone mineral density and biochemical markers of bone metabolism . DESIGN In this double-blind , prospective study , postmenopausal women were randomly assigned to one of four treatment groups : hysterectomized women were assigned to either 1 ) micronized E2 ( 0.5 mg ) or 2 ) micronized E2 ( 0.5 mg ) + micronized T ( 1.25 mg ) . Women with intact uteri were assigned to either 3 ) micronized E2 ( 0.5 mg ) + micronized P4 ( 100 mg ) or 4 ) micronized E2 ( 0.5 mg ) + micronized P4 ( 100 mcg ) + micronized T ( 1.25 mg ) . For the purpose of this study , the four treatment groups were combined into two groups for all comparisons . The E2 and E2+P4 groups were combined into the HRT alone group ( n=30 ) , and the E2+T and E2+P4+T groups were combined into the HRT + T group ( n=27 ) . Hormones were administered sublingually as a single tablet twice a day for 12 months . Bone mineral density was measured in the anterior-posterior lumbar spine and total left hip via dual energy x-ray absorptiometry . Bone metabolism was assessed via serum bone-specific alkaline phosphatase and urinary deoxypyridinoline and cross-linked N-telopeptide of type I collagen , both normalized to creatinine . Data were analyzed via a repeated measures analysis of variance and a Student 's t test ( alpha=0.05 ) . RESULTS The subjects were of similar age ( 54.0 +/- 0.8 years ) , height ( 64.0 +/- 0.3 in ) , weight ( 157.6 +/- 4.2 lb ) , and had similar baseline follicle-stimulating hormone ( 66.4 +/- 3.2 mIU/L ) , E2 ( 26.4 +/- 1.5 pg/ml ) , P4 ( 0.3 +/- 0.1 ng/ml ) , total T ( 19.0 +/- 1.5 ng/dL ) , and bioavailable T ( 3.7 +/- 0.3 ng/dL ) levels . During therapy , serum levels increased ( p < 0.05 ) for each hormone . Bone mineral density and bone markers at baseline were similar for each treatment group . Bone-specific alkaline phosphatase decreased ( p < 0.05 ) by -14.3 +/- 4.1 % in the HRT alone group and by -8.2 +/- 4.6 % in the HRT + T group . Deoxypyridinoline levels decreased significantly in the HRT alone and HRT + T groups , - 14.4 +/- 6.8 % and -26.9 +/- 7.6 % , respectively . Significant reductions ( p < 0.05 ) in cross-linked N-telopeptide of type I collagen were also observed in both groups , -24.4 +/- 6.5 % and -39.5 +/- 8.6 % , respectively . Bone mineral density in the lumbar spine increased ( p < 0.05 ) by +2.2 +/- 0.5 % the HRT alone group and by + 1.8 +/- 0.6 % in the HRT + T group . Total hip bone mineral density was maintained in the HRT alone group ( +0.4 +/- 0.4 % ) and increased ( p < 0.05 ) in the HRT + T group ( + 1.8 +/- 0.5 % ) . CONCLUSIONS Sublingual micronized HRT favorably decreases serum and urine markers of bone metabolism , prevents bone loss , and results in a slight increase in spine and hip bone mineral density . Although the addition of testosterone to HRT for 1 year did not result in added benefit to the spine bone mineral density , it did result in a significant increase in hip bone mineral density . Longer duration of therapy may have further improved these outcomes .
4380
Intervention_Pharmacological
micronized estradiol
4381
Intervention_Pharmacological
progesterone
4382
Intervention_Pharmacological
micronized testosterone
4383
Intervention_Pharmacological
micronized estradiol ( E2 )
4384
Intervention_Pharmacological
progesterone ( P4 )
4385
Intervention_Pharmacological
testosterone ( T )
4386
Intervention_Pharmacological
micronized E2
4387
Intervention_Pharmacological
micronized E2
4388
Intervention_Pharmacological
micronized T
4389
Intervention_Pharmacological
micronized E2
4390
Intervention_Pharmacological
micronized P4
4391
Intervention_Pharmacological
micronized E2
4392
Intervention_Pharmacological
+ micronized P4
4393
Intervention_Pharmacological
+ micronized T
4394
Intervention_Pharmacological
E2
4395
Intervention_Pharmacological
E2+P4
4396
Intervention_Pharmacological
E2+T
4397
Intervention_Pharmacological
E2+P4+T
4398
Intervention_Pharmacological
HRT + T
4399
Intervention_Pharmacological
HRT
4400
Intervention_Pharmacological
HRT + T
4401
Intervention_Pharmacological
HRT alone
4402
Intervention_Pharmacological
HRT + T
4403
Intervention_Pharmacological
HRT alone
4404
Intervention_Pharmacological
HRT + T
4405
Intervention_Pharmacological
HRT alone
4406
Intervention_Pharmacological
HRT + T
4407
Intervention_Pharmacological
HRT
4408
Intervention_Pharmacological
HRT
4409
Outcome_Physical
bone
4410
Outcome_Physical
and bone mineral density .
4411
Outcome_Physical
Bone mineral density
4412
Outcome_Physical
Bone metabolism
4413
Outcome_Physical
Bone mineral density and bone markers
4414
Outcome_Physical
Bone-specific alkaline phosphatase
4415
Outcome_Physical
levels
4416
Outcome_Physical
cross-linked N-telopeptide of type I collagen
4417
Outcome_Physical
Bone mineral density in the lumbar spine
4418
Outcome_Physical
Total hip bone mineral density
4419
Outcome_Physical
serum and urine markers of bone metabolism
4420
Outcome_Physical
bone loss
4421
Outcome_Physical
spine and hip bone mineral density .
4422
Outcome_Physical
spine bone mineral density
4423
Outcome_Physical
hip bone mineral density .
4424
Participant_Condition
biochemical markers of bone metabolism and bone mineral density .
4425
Participant_Condition
bone mineral density and biochemical markers of bone metabolism .