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Page 8 of 14 Mirastschijski et al. Plast Aesthet Res 2020;7:70 I http://dx.doi.org/10.20517/2347-9264.2020.147
[14]
reduced pro-inflammatory signalling of interleukin-6 and tumour necrosis factor (TNF)-α . Furthermore,
oestrogens are also important anti-oxidants that reduce cellular oxidative stress, apoptosis and increase
[15]
keratinocyte migration and collagen synthesis by dermal fibroblasts . In menopausal women, cutaneous
oestrogen insufficiency manifests by atrophic skin changes, vulvar and vaginal exsiccation, and diminished
defence against reactive oxygen species.

Hormonal influences on genital skin during menopause
As stated above, genital tissue is highly responsive to hormonal cues and changes. The menopause is a
major incident in a woman’s live with effects on her social, physical and psychological health. In 2014,
[16]
a variety of menopausal symptoms were classified as Genitourinary Syndrome of Menopause , which
[17]
includes vulvovaginal atrophy in 84% of menopausal women . Oestrogen insufficiency is the major
cause for menopausal skin symptoms such as dryness, decreased elasticity and hydration. 17-β-oestradiol
protects skin cells against oxidative stress, induces collagen production, controls cutaneous water content
and the dermal thickness. Oestrogen deprivation is followed by a decrease in tissue thickness and elasticity,
[18]
and a decrease in wound healing and scar formation . Regarding genital changes, mucous membranes of
small labia and vaginal tissue react with dryness and atrophy on low oestrogen levels . Topical oestrogen
[19]
[18]
application was successful in reversing atrophic changes of genital tissues .
Physiology of genital wound healing and scarring
Acute wound healing
Despite constant commensal colonization of genital skin and an absent cornified layer as a potent barrier
against microbial penetration, most genital wounds heal quickly and uneventfully. Communication with
colleagues from gynecology or urology mirrors our observations from genital reassignment or aesthetic
genital surgery. In contrast to skin of other body parts, genital wound healing is characterized by initial
swelling with fast resolution and by almost invisible scarring [Figure 4].

It is a well-known fact that wound healing is promoted by a moist environment - present on mucous
surfaces. Furthermore, inapparent scarring might be due to the fact that abundant elastic fibers are present
in genital skin compared to normal skin and to the absence of tissue tension due to lack of fixation to
underlying bone or cartilage. The disadvantage of the absent attachment to skeletal structures of genital
skin is its tendency to shrink when a chronic inflammatory stimulus is present [Figure 3].

Influence of microbial colonization
Surfaces of mucous epithelia are inhabited by a microflora that differs from normal skin as well. Despite
the missing cornified barrier and abundant commensal habitation, genital infections are rare (as in the
oral cavity) but in the event of bacterial penetration, infections can be disastrous with high mortality. One
example of a life-threatening genital infection is Fournier’s gangrene that can only be cured by extensive
and deep debridement of infected skin and underlying tissues as well as antibiotic therapy . Constant
[3]
exposure to commensal microbia is reflected by differential cellular immune responses with higher
expression of antimicrobial peptides (AMPs) and defensins. The immune response and resolution are fast
[15]
with conversion of M1 to M2 macrophages and reduced expression of pro-inflammatory cytokines . Upon
injury, skin cells increase IL-1α production 15-fold in comparison to vaginal epithelial cells which show
only a 3-fold increase. IL-1β and TNF-α are secreted by cutaneous epithelia in contrast to mucous epithelial
cells . With regard to pro-fibrotic mediators, transforming growth factor (TGF)-β is significantly elevated
[20]
in normal skin keratinocytes but not in mucosal epithelia and without induction of fibrotic processes in
the underlying connective tissue. In summary, the reduced inflammatory response of mucosal epithelia to
injury ensures fast wound closure.