Postmenopause is characterized by several changes due to a physiological reduction in the ovarian production of steroidal hormones.22–24
This creates a hypoestrogen state that can provoke significant phenomena such as hot flashes, decreased libido, loss of bone mass and atrophy of the genitourinary tract and skin.17
Following the Raine-Fenning et al.25
study, several authors identified a progressive decrease in dermal collagen concentrations, skin drying and even skin atrophy after menopause. We note that these latter phenomena, related to the drop in circulating estrogens, manifest in a number of ways. In some postmenopausal women the changes occur slowly, but in others the onset can be very fast.26
To eliminate or at least minimize the deleterious effects of estrogen deficiency, estrogen therapy is not only directed at the early symptoms (hot flashes) but also aims to arrest certain well-known menopausal conditions such as osteoporosis and skin atrophy.11,27
Data in the literature has shown that long-term estrogen treatment is effective in increasing skin thickness in postmenopausal women.15, 28, 29
Despite the known beneficial effects of hormonal therapy, compliance rates are low, ranging from 10 to 30%.17, 30
Given this fact, alternative therapeutic options are required for women who do not accept or who have some contraindication to classical hormonal therapy in the postmenopausal period. Of the available alternatives, phytoestrogens (especially isoflavones) are often highlighted, with particular emphasis on concentrated, isoflavone-rich soy extracts.
Isoflavones appear to exhibit biological activities similar to estrogen because they are heterocyclic phenolic compounds with structural similarities to both natural and synthetic estrogens.31–33
Certain authors have reported that isoflavone effects depend on the plasma concentrations of their corresponding aglycones, such as genistein and daidzein.34
In addition, we note that the metabolites of these substances may also exhibit biological activity. Among these, equol, the final product of daidzein biotransformation, has clear estrogen-like activity and displays affinity for both the α and β estrogen receptors. Also, it is superior to other isoflavones with regards to antioxidant activity.35
Cai and Wei36
have demonstrated that ingesting soy isoflavone (genistein) for 30 days significantly increases the activity of the antioxidant enzyme superoxide dismutase in various mouse organs. The largest increases of antioxidant enzyme activity were observed in the intestine and on the skin.
Many studies have shown that isoflavones may impact the skin.37,38
The results presented herein show an increase in the epidermal and dermal skin thickness after a six-month treatment program with a concentrated soy extract at a dose of 100 mg per day. In addition to an increase in the epidermal thickness, we also found increases in the papillary index, quantity of collagen and elastic fibers, and number of dermal vessels.
Kotsopoulos et al.37
conducted a double-blind, placebo-controlled study involving 94 postmenopausal women aged 50 to 75 years. They each received an isoflavone-enriched high-protein diet. The study reported an enhancement in the moisture content of facial skin, with a significant decrease in drying after three months of treatment. By contrast, Tomaszewski et al.38
evaluated human skin fibroblasts in cell culture, and reported an increase in collagen production after treatment with isoflavones, although this effect was less than that induced by estrogen.
Despite minimal evidence supporting isoflavone action on skin, there are reports that genistein may exert protective effects on aging skin as well as reducing the risk of skin carcinoma induced by ultraviolet irradiation, an effect presumably related to the inhibition of dermal tyrosine kinases in animals.39
However, there is inconsistent evidence that this would happen in menopausal women.37
The effect of estrogens on the thickness of the skin epithelial layer is well understood. Fuchs et al.29
reported a 23% increase in epithelium thickness after six months of treatment with topical estrogens. In animals, Calil et al.40
have shown that treatment with equine conjugated estrogens increases the epithelial thickness of the skin of adult ovariectomized mice. Accordingly, isoflavones should improve the skin epithelium (thickness and papillar index) by binding to estrogen receptors, thereby promoting cellular proliferation.41
Besides epithelial cells, estrogen receptors are found in other skin components such as in fibroblasts. In these cells, estrogens act by reducing metalloprotease activity in the skin. Therefore, this should result in less degradation of skin collagen fibers during estrogen treatments.42
We emphasize that collagen is responsible for both skin structure and strength. In addition, estrogenic action enhances the concentration of glycosaminoglycans, thus elevating skin water content and consequently increasing skin turgor.43
Our results suggest an increase in the number of skin elastic and collagen fibers. This effect would presumably be mediated by the activation of the estrogen receptor, although the exact subtype that is activated cannot be defined at present.
Many clinical studies in postmenopausal women suggest that skin thickness is greater in those who have been treated with estrogens than in those who have not. This effect is more evident after at least one year of treatment, 44,45
although this effect has also been shown with much shorter treatment durations.44
Conceivably, the increase in collagen content after treatment with concentrated soy extract could be explained by an estrogen-like action of isoflavones.
As reported elsewhere, skin aging is not totally dependent on estrogen. Many other factors such as ultraviolet radiation (UV) can accelerate the degradation of skin components and the apoptosis of both epithelial and dermal cells.45
In animals, treatment with isoflavones offers protection against the initiation and promotion of photocarcinogens in the skin induced by UV radiation.37,46,47
Besides this, topical application of genistein can protect against the erythremia caused by UV radiation in humans.39
The mechanism of action of isoflavones on skin may not only be dependent on an estrogen-like mechanism, but might also involve the participation of antioxidants.39
Skin hydration depends on both the number of vessels and their responsiveness. In postmenopausal patients, the skin tends to progressively dry out and subcutaneous capillaries disappear. Though estrogens increase the concentrations of epidermal and vascular-endothelial growing factors, estrogenic therapy is unable to restore the cutaneous microvasculature after six months of treatment.48
Skin vessel maintenance/growth mechanisms are probably related to a complex array of cellular factors, some of which may be independent of the estrogen receptor.
Finally, our data have shown that the administration of a concentrated soy extract for six months can provide definite benefits. We note improvements in skin health for the postmenopausal women in our study, mainly through increased epithelium thickness, elevated concentrations of collagen and elastic fibers, and an increased number of subcutaneous vessels. Presumably, these same effects could also protect skin against the deleterious effects of UV radiation. Isoflavone therapy is worthy of further investigation and should be compared to results obtained in the treatment of postmenopausal women with a standard replacement estrogenic therapy.