Ageing is an inevitable factor in life. In women, this process is accelerated when they enter the peri-menopause, which is associated with a decline in ovarian function and falling levels of oestrogen. Oestrogen exerts numerous effects throughout the body, therefore it is unsurprising that the skin, as the largest organ in the body, is profoundly impacted by waning levels of oestrogen associated with the peri- and post-menopausal state. The main cell types found throughout the different layers of the skin possess receptors which respond to oestrogen, therefore when the influence of oestrogen is withdrawn, there can be numerous outcomes.1,2,3 Fortunately, whilst ageing is inevitable, your patients looking their age is not.
Menopause and skin ageing
Menopause is associated with low levels of oestrogen, otherwise referred to as a hypo-oestrogenic state.1 This significant hormonal change is associated with a loss of skin structural architecture and an increased susceptibility to damage.4 Arguably, a hypo-oestrogenic state represents the most significant intrinsic cause of ageing in women with its association with an acceleration in skin dryness, thinner skin, fine lines and wrinkles, reduced firmness and elasticity, and photodamage.4
As women enter the peri-menopause one of the first changes noted in the skin, and arguably the most significant change, is the appearance of dry and itchy skin.4 Oestrogen promotes skin hydration by elevating levels of mucopolysaccharides to keep the skin lubricated and moisturised.4 Oestrogen also promotes the production of hyaluronic acid within the dermis. Hyaluronic acid is hydrophilic, therefore it draws in water which keeps the skin hydrated and maintains skin turgor and fullness.5 Additionally, oestrogen also encourages the production of ceramides, which are epidermal lipids that help retain moisture within the skin and maintain a healthy skin barrier.6 Menopausal women also experience a significant decline in circulating testosterone, which usually promotes the production of sebum from sebaceous glands.7 The end result leaves the skin deprived of its natural hydrating agents, culminating in very dry and itchy skin.
Another consequence of waning oestrogen is epidermal thinning. This can largely be attributed to reduced collagen synthesis and increased collagen degradation.8 Additionally, a decrease in mitosis, the process of cell division for growth and replacement of old cells, also leads to thinner skin. This is a direct consequence of reduced oestrogen, which in pre-menopausal states stimulates mitosis in keratinocytes.5,9 Evidence shows that up to 30% of dermal collagen may be lost during the first five years following the menopause, with collagen content further decreasing by approximately 1-2% each year thereafter.2,3,4 This is associated with a decrease in skin thickness by 1.1% per year.4 The end result is a combination of thin, sagging, dry skin, the opposite to pre-menopausal youthful skin.10
Fine lines and wrinkles
The appearance of fine lines and wrinkles is significantly influenced by hormonal factors, with the post-menopausal state being associated with increased wrinkling.5 It has been shown that low levels of oestrogen increase the propensity to form wrinkles, and the application of oestrogen cream significantly improves the appearance of fine lines and wrinkles.1 A large cohort study performed in America, including almost 4,000 post-menopausal women, found that the use of oestrogen replacement therapy prevented the development of skin rhytids.11 This can be explained by the increase in skin collagen content and glycosaminoglycans in the presence of oestrogen.1,3,5,12 Additionally, increased formation of wrinkles is associated with, and exacerbated by, a decrease in skin elasticity, which is observed in the menopause. In post-menopausal women, skin elasticity reduces by approximately 1.5% per year, a decrease that is not similarly observed in women taking hormone replacement therapy (HRT).5 Moreover, topical oestrogen appears to thicken elastic fibres in the dermis, increase their quantity, and improve their orientation. It can therefore be deduced that a lack of oestrogen will contribute to wrinkle formation through a reduction in skin elasticity.5,11
Finally, it is important to recognise that oestrogen has important antioxidant properties which provide a protective role against skin ageing associated with photodamage. Following exposure to ultraviolet radiation, post-menopausal skin is much more susceptible to skin damage. An increased formation of deep wrinkles, skin sagging and decreased skin elasticity are all seen following ultraviolet exposure in post-menopausal skin as a direct consequence of oestrogen deficiency.5 This occurs due to an increase in elastase-mediated degradation of elastic fibres found within the dermis.8,11 Furthermore, oestrogen has the capacity to switch off enzymes, known as matrix metalloproteinases (MMPs), which accelerate skin cell damage, thereby counteracting the potential damage inflicted by reactive oxygen species generated from ultraviolet rays from the sun.5,13 This powerful hormone can also activate proteins, such as nuclear factor erythroid 2-related factor (NRf2), which increase the expression of further antioxidants and detoxifying enzymes.10 This may protect against skin damage and subsequent ageing.10
Hormone replacement therapy
To tackle the signs of ageing skin associated with the menopause we must address the underlying cause, oestrogen deficiency. Therefore, arguably the most important preventative and restorative treatment option for ageing skin is the replacement of oestrogen in the form of HRT.14 There is a plethora of routes to administer HRT, including oral tablets, transdermal via gel, patch or spray, and local application of oestrogen pessaries and creams. The optimal HRT regimen utilises body identical HRT, which involves a combination of transdermal oestrogen and micronised progesterone.15 With the recent advancements in accessibility to localised vaginal oestrogen tablets, now available without prescription, we can hope overall accessibility to systemic HRT will similarly improve in the future.15
The use of oestrogen is associated with increased collagen content, increased dermal thickness, improved skin elasticity, reduced wrinkle formation, and a reduced propensity to develop dry skin.16,17 Studies have shown that women who used HRT continuously within one year of their last menstrual period had significantly fewer wrinkles and less skin rigidity.4,17,18 Undeniably, systemic HRT is generally not advocated to solely treat skin ageing. However, it could be considered at the forefront of treatment options.
There is significant bone loss associated with the menopause, including from the facial skeleton.19 The resulting deficiencies in the skeletal framework contributes to ageing by the development of prominent nasolabial folds, tear trough deformities, and jowls, and leads to a dwindling contoured appearance of the face.20 The early use of HRT prevents bony resorption and thereby, helps to maintain skeletal structure which has the potential to counteract premature facial ageing.19,20 However, as previously alluded to, HRT is not licensed for antiageing purposes and a comprehensive consultation is fundamental prior to initiation to exclude any contraindications to prescription, and to fully explore the small risks associated with HRT, which are the risk of breast cancer and blood clot.15
To tackle the signs of ageing skin associated with the menopause we must address the underlying cause of oestrogen deficiency
There is an irrefutable correlation between skin collagen loss and oestrogen deficiency. Therefore, it is important to incorporate key ingredients into a skincare regime to promote collagen production. Vitamin A-derived products, such as retinol and retinoids, help to counteract collagen loss by stimulating collagen production whilst simultaneously protecting against collagen degradation.21 This directly helps to minimise the appearance of wrinkles and the loss of skin firmness and elasticity. Vitamin A-derived products have also been shown to improve epidermal thickness, provide antioxidant protection and regulate sebum production.21 Another important ingredient to encourage collagen production is vitamin C, which stimulates collagen production and stabilises the collagen molecule by a process called hydroxylation.22 However, it is important to recognise that the penetration of vitamin C in topical skincare products is variable. It is only when vitamin C is present as ascorbic acid and the pH level is below four that penetration occurs.22
As described earlier, menopausal skin is classically dry due to the reduction of sebum, ceramides and hyaluronic acid. Therefore, the use of a daily ‘moisturiser’ is essential to retain water content and prevent water evaporation from the skin surface. ‘Moisturiser’ is an umbrella term which encompasses humectants, occlusives, and emollients.23 Each possess their own mechanism of action but similarly result in improved skin hydration and increased water content within the stratum corneum by directly providing water to the skin and increasing occlusion to prevent water loss across the epidermis. However, not all moisturisers are made the same, and whilst some will contain ingredients to improve the skin barrier function and improve overall skin health, others may exacerbate skin dryness and weaken the skin barrier.24,25,26 Table 1 illustrates some examples of humectants, occlusives and emollients which represent the key ingredients to look for in a moisturising product.23
Oestrogen stimulates the production of hyaluronic acid (HA) within the deep dermis of the skin.5 Therefore, topical application of HA, which sits on top of the outer surface of the skin, will not have the same effects as intrinsic production which draws water in, restores skin fullness, maintains skin turgor and reduces fine lines. Therefore, to replenish levels of HA within both the epidermis and dermis, injections could be considered in the form of bioremodelling treatments and HA-based dermal fillers.2
Bio-remodelling treatments aim to increase the biosynthetic capacity of fibroblasts, inducing the restoration of an optimal physiological environment, the enhancement of cellular activity, hydration, and the synthesis of HA, collagen and elastin.2
The benefits of HA-based dermal fillers go beyond enhancing HA levels within the dermis. Dermal fillers can also be used to address the bony resorption process, which is seen at an accelerated rate in the menopause.19 In addition, dermal fillers can also be used to tackle skin atrophy, which is inevitable in the menopause, restore facial volume and soften the appearance of fine lines and wrinkles associated with ageing.1,27
A discussion about treatments for menopausal skin ageing would not be complete without reference to the use of botulinum toxin A injections. Whilst it will not improve skin texture or quality, and will not reverse the hormonal skin changes associated with the menopause, it can impede the visible ageing process by reducing the appearance of fine lines and wrinkles.2
A holistic approach
The influence of oestrogen on the skin cannot be underestimated and the acceleration of skin ageing as oestrogen levels start to fall is overwhelming. It is important that healthcare professionals have an understanding and appreciation of this to be able to comprehensively address the skin care concerns of peri- and post-menopausal women. Undeniably, a holistic approach to treatment is needed which encompasses lifestyle modifications, HRT, skincare products and, where desired, injectables too.
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