Effects of hormone replacement therapy and tibolone on skin thickness and bone in postmenopausal women.

To the Editor: This prospective, randomized study was under-taken to investigate the effects of hormone replacement therapy (HRT) and tibolone (T) on skin by ultrasonographic and histologic evaluation and on bone by bone mineral density (BMD). Forty nonsmoking postmenopausal women were randomized by block randomization to HRT or T. Of the 20 women in the HRT group, one had undergone hysterectomy and received conjugated equine estrogens 0.625 mg daily (Premarin, Wyeth); 19 women received conjugated equine estrogens 0.625 mg, medroxyprogesterone acetate 5 mg daily continously (Premelle 5, Wyeth). The 20 women in the T group received tibolone 2.5 mg daily continuously (Livial, Organon). Both groups were treated for 12 months. One women in the HRT group and 3 women in the T group did not complete the study.

Skin thickness was measured by ultrasonography, three times (at initiation, at 6th and 12th months). Evaluations were performed at the right thigh 3 c m below the greater trochanter. Skin biopsies were performed two times (at initiation and at 12th month) at the marked location. BMD in the lumbar spine was measured by dual X-ray absorpsiometry (DXA) at initiation and at 12 months. When estimations were done for comparisons within each group using the ANOVA method, 11%±26% (mean±SD) of change could be detected with an α level of .05 and a power of 78%. The demographic characteristics (age, body mass index, menopause time, gravida, parity) of the two groups were comparable.

When evaluated by ultrasonography, a statistically significant increase in skin thickness compared with baseline was observed after 12 months of treatment (P=0.002) and from 6 to 12 months (P=0.001) within the HRT group (Table 1), but there was no statistically significant changes after the first 6 months compared with baseline (P=0.68). In the T group, the increase in skin thickness was statistically significant from baseline to the 6th and 12th months (P=0.01 and P=0.01)) but not between the 6th and 12th months (P=0.53). The tibolone group showed a significant increase on the ultrasonographic skin thickness measurement at the 6th month visit compared with the HRT group (P=0.03). Histologic skin thickness differences at 12 months were not statistically significant compared with baseline in either the HRT (P=0.289) or T groups (P=0.996) (Table 2). There were no group differences in the histologic skin thickness measurements (P=0.29).There were statistically significant changes in T score after 12 months of treatment in the two treatment groups (P=0.007 in the HRT group, P=0.027 in the T group), but the responses in the two treatment groups were not significantly different from each other (P=0.269).

Table 1

Skin thickness by ultrasonography at baseline, and 6th and 12th months.

	Group HRT (n=19)	Group T (n=17)
Baseline	1.989 ± 0.395	2.156 ± 0.378
6th month	1.956 ± 0.383	2.340 ± 0.308*†
12th month	2.222 ±0.407‡	2.393 ± 0.281†

P<0.05 vs HRT

P<0.05 vs. baseline

P<0.05 vs. baseline and 6th month

Table 2

Baseline and 12 month measurements of skin thickness by skin biopsy and T scores for BMD.

	Group HRT (n=19)		Group T (n=17)
	Skin thickness (mm)	BMD (T score)	Skin thickness (mm)	BMD (T score)
Baseline	3.070±1.134	−1.36 ± 1.02	2.784±1.116	−1.51±1.01
12th month	2.565±1.088	−1.09±0.97*	2.782±1.239	−1.34±1.07*

P< 0.05 vs. baseline

Most studies have measured the thickness of dermis, and dermis is composed virtually entirely of connective tissue. Subcutaneous tissue is an added variable and inclusion of the subcutaneous fat in the measurements results in uncertainty.1 Therefore in order to obtain good accuracy in the measurements, high frequency ultrasonography has been used to determine skin thickness. Our study supports these results with the ultrasound technique, a sensitive, reproducible and valid technique for measurement of skin thickness.

Dermis thickness in skin biopsy may show wide variations related to how the specimen is cut; if the cut is not perpendicular to the skin surface, the thickness measurement will not be correct. 2 In concordance with others, significant increases in skin thickness were observed on the sonographic evaluation in our study, but not in the histologic examination in the two treatment groups. Skin and bone changes with estrogen deficiency at the menopause have been shown to be isochronal events.3 In our results, both HRT or tibolone therapy was associated with increases in T scores. Although a small series, our results showed that HRT and tibolone had a benefical effect on skin thickness and on BMD in postmenopausal women.