Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia

Staniaław Stanosz, Ewa Zochowska, Krzysztof Safranow, Krzysztof Sieja, Małgorzta Stanosz
Metabolism: Clinical and Experimental 2009, 58 (1): 1-7
The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 +/- 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17beta-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E(1)) was increased about 11-fold in the group of women receiving orally given HST (P < .0001) compared with control group. Estrone and estradiol levels were increased about 3-fold in women receiving modified transdermal HRT compared with the baseline values. Basal PRL concentration and PRL level after metoclopramide stimulation test significantly increased after 3 and 12 months of treatment in the group receiving orally given HST. In women receiving modified transdermal HRT, increased IGF-I concentrations were statistically significant after 3 months of treatment. In the group of women receiving orally given HST, a significant decrease of IGF-I after 1 year therapy was found. During the entire time of treatment in this group, an increase of growth hormone was observed. No significant changes were shown in osteocalcin and in carboxyterminal propeptide of type I procollagen in all groups. Increase in bone mineral density L(2)-L(4) was statistically significant in the group receiving modified transdermal HRT (P < .01) and was insignificant in women receiving orally given HST after 12 months of therapy as compared with baseline values. Following are the conclusions: (1) Low-dose modified transdermal HRT modulates concentration of hormones, growth factor, IGF-I, osteocalcin, procollagen, and bone metabolism. (2) The curve concentrations of estrogens and progesterone in serum are similar to the type observed in the physiologic menstrual cycle. (3) The lack of significant increase in bone mineral density of lumbar spine in women after HST may be a result of significantly lower concentration of IGF-I in serum and occurring hyperprolactinemia.

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