The human male skin is thicker and drier than the female skin from the age of 5 through 90. In men, linear decline in skin thickness is observed from age 20 onwards. However, in women, skin thickness remains constant until menopause and thereafter declines drastically. The decrease in thickness of the epidermis is on average about 6.4 % per decade, whereas dermal thickness decreases by up to 20 %. Thinning of aging skin is mainly due to reduction of dermal thickness [13].

Collagen, elastin, and hyaluronic acid are the major extracellular components of the dermis. Collagen provides the required tensile strength. Type I (80 %) and type III (15 %) are most prevalent in the human skin among over 14 types of collagen. Collagen fibers become sparse, thicker, and increasingly disorganized with age thereby disrupting the tension on dermal fibroblasts. In addition, elastin turnover also declines with age. Thus, the skin becomes less elastic, less extensible under force, and more vulnerable to injury by shear forces. In women, collagen content declines at an average of 2.1 % per year for the first 15 postmenopausal years [14]. Women receiving hormone replacement therapy (HRT) showed no such reduction in skin thickness [15]. Also, oral, topical, or subcutaneous estrogen supplementation has also shown to increase collagen content [14].

Dehydroepiandrosterone (DHEA) regulates the turnover of extracellular matrix protein by promoting procollagen synthesis by decreasing the synthesis of collagenase and matrix metalloproteases and limiting collagen degradation by increasing the production of tissue inhibitor of matrix metalloproteinase. DHEA, the primary source of sex steroid production in the skin, declines tangibly with age, resulting in lower procollagen synthesis and higher collagen degradation. Baulieu et al. showed that oral DHEA treatment in men and women aged 60–79 improved epidermal thickness and skin hydration, increased sebum production, and reduced facial pigmentation, with effects being more dramatic in women over 70 than in men [16].

Though the interplay between estrogens and androgens is not clearly understood, androgens are known to affect epidermal hyperplasia in humans, which may partly contribute to greater skin thickness in men and in women with excess of androgen [7].

Another important sign of aging skin is dryness. The water-holding capacity of both the epidermis and the dermis is affected by age with no significant gender-related difference [17]. The water content of the stratum corneum, which is related to skin barrier function and the composition and organization of stratum corneum lipids, is much lower in aged skin [18]. Aging fibroblasts produce lower levels of glycosaminoglycans and hyaluronic acid, thereby reducing the water-holding capacity of the dermis [19]. Schmidt et al. showed that topical estradiol 0.01 % and estriol 0.3 % improved skin moisture in perimenopausal or postmenopausal women [20]. Also, a large population-based cohort study demonstrated that postmenopausal women taking HRT were less likely to experience dry skin as compared to those not taking HRT [21]. Estrogen is known to increase acid mucopolysaccharides and hyaluronic acid in the dermis which leads to increase in dermal water content [22]. Also, the higher levels of sebum in postmenopausal women receiving HRT suggest that estrogen may prevent the decrease in glandular secretion otherwise seen in aging skin [23]. Estrogen therapy also leads to increased water-holding capacity of the stratum corneum and a decrease in the rate of water accumulation in postmenopausal women, thereby improving the ability of the stratum corneum to prevent water loss [24, 25]. Estrogen enhancement of skin barrier function potentially aids in maintaining homeostasis [26].

Loss of skin elasticity, epidermal thickness, and elastic degradation results in skin wrinkling. The study by Henry et al. demonstrated that facial skin wrinkling is characterized by an increase in extensibility and decrease in elasticity [27]. Topical application of estrogen results in significant decrease in fine wrinkles and wrinkle depth [20, 21]. The observed improvement in skin wrinkles by estrogen is due to its ability to increase the proportion of type III collagen. The application of estriol ointments to the skin of postmenopausal women also leads to histologic changes of the skin in some individuals. These changes include thickening of the elastic fibers in the papillary dermis. The elastic fibers were also noted to be in better orientation and slightly increased in number. Estrogen causes an increase in the hyaluronic acid in the dermis which improves the water-holding capacity. Thus, HRT seems to improve skin wrinkling in postmenopausal women. However, Castelo-Branco et al. pointed out this improvement is seen only in nonsmoking women and not in smokers. This is possibly due to the side effects of tobacco use, which include a destruction of the ground substance, decreased blood flow in the skin, and direct toxic effects of tobacco [28].

Sebum levels stay consistent in men after puberty until age 80, whereas in women, a gradual decrease in sebum secretion is observed from menopause through the 70s. Estrogen deprivation also affects sebum production, causing skin dryness [23, 29]. HRT showed a 35 % increase in sebum levels in postmenopausal women [30]. Estrogen appears to increase sebum production primarily by regulating the expression of insulin-like growth factor (IGF)-1 receptors and increasing the production of IGF-1 from fibroblasts. Increased IGF-1, in turn, induces lipogenesis in human sebocytes via the phosphatidylinositol 3 kinase-stimulated pathway, leading to increased sebum production in the skin [31].

Aged skin is more vulnerable to shear forces due to increased fragility caused by the flattening of the dermoepidermal junctions [32]. In the aged, wound healing is slower to start and slower to proceed. Epidermal turnover slows by 30–50 % between the third and eighth decades and the tensile strength also decreased after age 70 [33]. In general, men show slower wound healing than women at all ages. Wound healing is influenced by the balance of circulating estrogens and androgens and gender differences in the response to the hormones. Keratinocytes on wound edge, infiltrating inflammatory cells, and dermal fibroblasts express AR. Androgens increase local inflammation and promote excessive proteolysis, which depress wound healing [34]. Androgens delay regression of inflammatory response as well as matrix degradation. Induction of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) that promote wound healing is defective in elderly people [35]. DHT also inhibits wound closure by affecting the migration of epidermal keratinocytes [35]. Estrogens are very critical to the process of wound healing; estrogen inhibits inflammation and promotes deposition of matrix components [36]. Estrogen’s mitogenic effect on keratinocytes increases re-epitheliazation of wounds [37]. In postmenopausal women with impaired wound healing, estrogen treatment accelerates re-epithelization and local collagen deposition. Estrogen also regulates the expression of macrophage inhibitory factor (MIF), a proinflammatory cytokine involved in hormonal regulation of wound healing [38].

Estrogen receptors are present on nearly every type of cell in the immune system including β cells, CD4+T cells, CD8 +T cells, dendritic cells, macrophages, mast cells, neutrophils, and thymocytes [39]. Estrogen exposure activates ER at the cell membrane to modulate signal transduction cascades [40]. Estrogen produces thymic atrophy and decreases the number and function of thymocytes which in turn downregulates T-cell mediated immune function [41]. Estrogens enhance humoral immunity by stimulating CD4+TH2 cells and β cells. Systemic lupus erythematosus (SLE), an autoimmune disease with a female-to-male ratio of 3:1 before puberty, 10–15:1 during the reproductive years, and 8:1 after menopause, has higher prevalence in menopausal women taking estrogen supplement [42]. Scleroderma and rheumatoid arthritis (RA) are some of the other autoimmune diseases which seem to be affected by sex hormones. It is increasingly evident that women have to cope with the immune-inducing effects of increased estrogen levels during reproductive years and after menopause, increased autoreactive monocyte survival as a result of decreased activation of the Fas/Fas ligand system due to decrease in estrogen levels [13].

Remarkable gender differences are observed in hair growth, since both androgens and estrogens affect hair follicle stimulation [43]. Androgenic effects on hair follicles are mediated by DHT, produced by 5α-reductase from testosterone. DHT interacts with AR on dermal papilla cells, which causes release of growth factors that act on other cells in the hair follicle. In androgen-dependent areas such as the male beard and pubic hair, androgens promote enlargement of hair follicles, whereas they also cause miniaturization of scalp follicles, leading to male pattern baldness [44]. Female pattern hair loss (FPHL), usually involving the frontal and parietal scalp areas and independent of androgen levels, begins after age 30 and is more prevalent after menopause. Women’s frontal and occipital hair follicles have less than one-third 5α-reductase and 40 % lower AR levels compared to men [45]. Scalp hair follicles express six times more aromatase activity in women than in men, leading to formation of estrogen from testosterone which probably acts as a protective factor [46]. Hair loss (alopecia) and hirsutism are two major changes seen during menopause. The most common form of alopecia in elderly women [47] is FPHL. The amount of body hair in women keeps increasing until menopause, after which it begins to decrease. In contrast, facial hair increases even after menopause [48].

Unlike the bulk of cutaneous epithelium, the vulvar area derives from three different embryonic layers. The cutaneous epithelia of the mons pubis, labia, and clitoris, which originate from the embryonic ectoderm, exhibit keratinized, stratified structure. The nonkeratinized mucosa of the vulvar vestibule originates from the embryonic ectoderm. The vagina, derived from the embryonic mesoderm, is mainly responsive to estrogen cycling. Hormonal changes at menopause perturb morphological and physiological changes of the vulva and vagina. After menopause, the vaginal epithelium and the labia atrophies, cervicovaginal secretions reduce, vaginal pH rises, atrophic vaginitis becomes more common, collagen and water content decrease, pubic hair becomes sparse and gray, and the labia majora loses subcutaneous fat. The thinned and dry tissue is more susceptible to irritation and infection [49].