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Reilly et al. Plast Aesthet Res 2021;8:2 I http://dx.doi.org/10.20517/2347-9264.2020.153 Page 11 of 24

Figure 8. For women presenting regular or irregular menstrual cycle there was no discernible difference in collagen content in skin.
However, for the post-menopausal cohort the trend shows an approximately 13% decrease in collagen content of the skin. (By
permission of MINERVA Research Labs Ltd - London)

[45]
the collagen content was reduced in women of post-menopausal status [Figure 8] . Results indicated a
decrease in collagen score measured in post-menopausal women (Percent Collagen Score = 59.8 ± 18.1, n =
27) compared to pre-menopausal subjects (Percent Collagen Score = 67.9 ± 12.1, n = 38). Intriguingly there
was no direct correlation between women presenting regular or irregular menstrual cycle while carrying
out the study (Percent Collagen Score = 67.4 ± 12.5, n = 25 and 68.9 ± 11.7, n = 13, respectively).

Researchers have explored innovative strategies using oestrogen-related treatments to help improve skin
conditions [65,66] . Although the effects of oestrogen on the skin are still not fully understood, it is known that,
in women declining oestrogen levels are associated with a variety of cutaneous changes, many of which
can be reversed or improved by supplementation with estrogenic-like substances. Hormone Replacement
Therapy (HRT) is a treatment to relive symptoms of the menopause, usually combining oestrogen and
progesterone. It replaces systemic hormones that occur at a lower level as progression of the menopause
occurs. The key benefits of HRT are to help restore collagen in skin, relieve hot flushes, reduce night-
sweats, control mood swings, decrease vaginal dryness, among others.

HRT oestrogen with or without progesterone has been used to treat menopausal symptoms and to prevent
long-term conditions such as osteoporosis and cardiovascular disease. In a randomized placebo-controlled
trial were evaluated the effects of genistein on hot flushes in postmenopausal women for 1 year. The flush
[67]
score decreased by 24% with genistein compared to 54% with synthetic hormone analogues used in HRT .
Isoflavones and lignans are the two main groups of phytoestrogens (PE). Isoflavones are polyphenolic
compounds that possess both oestrogen-agonist and oestrogen-antagonist properties. Isoflavone
compounds, such as genistein and daidzein are mainly found in soybean-based products. Genistein is the
most widely studied isoflavone, is an angiogenesis inhibitor and a phytoestrogen with antioxidant properties
having beneficial effects on human degenerative diseases. Daidzein, on the other hand, has been shown
[68]
to increase fibroblast proliferation in fibromuscular coat of the vaginal epithelium and in human skin .
In another double-blind placebo-controlled clinical trial, researchers studied the effects of isoflavones
on menopausal symptoms, including dry skin, facial hair, libido, and vaginal dryness in postmenopausal
women aged 50 to 75 years. Three months of soy supplements containing PE did not provide symptomatic
[69]
relief compared with placebo . Unfortunately, there are still insufficient data to understand the long-term
implications of PE use.