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Gender-linked differences in human skin
Journal of Dermatological Science 55 (2009) 144–149
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Journal of Dermatological Science journal homepage: www.intl.elsevierhealth.com/journals/jods
Review article
Gender-linked differences in human skin Paolo U. Giacomoni a,b,*, Thomas Mammone a,b, Matthew Teri b a b
Clinique Laboratories, Melville, NY, United States Estee Lauder Companies, New York, NY, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 27 April 2009 Received in revised form 11 May 2009 Accepted 2 June 2009
Background: The physiology of body organs can be affected by gender. Skin and skin appendages are influenced by sex hormones. Objective: This review work has been undertaken to point out the most conspicuous physiological differences observed between men’s and women’s skin. Methods: The literature has been searched and relevant results have been gathered. Results: Men’s and women’s skins differ in hormone metabolism, hair growth, sweat rate, sebum production, surface pH, fat accumulation, serum leptins, etc. Examples of differences in the proneness to cutaneous diseases and skin cancer are quoted. Conclusion: The knowledge of gender-linked cutaneous differences might help in preparing malespecific products for more appropriate dermatological treatments or cosmetic interventions. ß 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Human skin Gender-linked differences Physiology Aging
Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hormones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Facial and body hair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sebum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sweat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Surface pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin thickness, collagen and water retention . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin tone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Immune systems and skin cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Healing and other surface properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin sensorial properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Muscular mass and body fat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cosmetic and dermatological implications based on gender differences in skin References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Gender-linked physiological differences have been pointed out in body organs of healthy and diseased subjects, comprising the skin. The skin controls the gaseous exchanges with the exterior, regulates the thermal equilibrium of the body, contains sensory organs to interact with the environment, harbors saprofite microflora, provides a physical barrier against the penetration of
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inorganic matter, and a biochemical defense against viruses and other pathogens. It also provides a cushion against traumatisms and is equipped with dendritic cells to trigger immune responses. This review summarizes anatomical, physiological and biochemical differences between male and female skin (summarized in Table 1) and discusses how this knowledge may contribute to the improvement of skin care interventions, particularly for men. 2. Hormones
* Corresponding author at: Clinique Laboratories, 125 Pinelawn Road, Melville, NY 11747, United States. Tel.: +1 631 531 1238. E-mail address: [email protected] (P.U. Giacomoni).
Men and women skin differ in the metabolism of sex hormones, and in the response to them [1]. Testosterone is synthesized in the testes, in the ovaries and in the adrenal cortex. It is converted to
0923-1811/$36.00 ß 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jdermsci.2009.06.001
P.U. Giacomoni et al. / Journal of Dermatological Science 55 (2009) 144–149 Table 1 Gender-linked differences in human skin. Characteristics
Males
Females
Ref.
Sweat rate during exercise (ml/h) Sebum (mg/cm2) pH (surface) pH (intra-epidermal) Leptin (serum level, ng/ml) Skin thickness (ratio men/women) SCC (incidence ratio men/women) Systemic lupus (incidence ratio men/women) Melanoma (mortality ratio men/women)
800 3 5.8 4.6 16
450 0.7 5.5 5.6 3
[6] [10] [17] [10] [65] [19] [42] [41] [41]
1.2 2 0.11 2
de-hydro-testosterone by 5-a-reductase. Estrogen and progesterone are synthesized in the ovaries. Present at birth, their levels increase during adolescence and their quantitative difference determines the secondary sexual characteristics of the individual. Skin is a steroidogenic tissue: it metabolizes sex hormones and responds to them [2]. Aromatase converts testosterone to estradiol in women’s skin, where excess testoserone can lead to androgenic-dependent alopecia or to hirsutism. In men, beard growth and male-pattern hair loss are abolished when testosterone is removed [1]. A sexual dimorphism has been pointed out also in the levels of non-sexual hormones. Men have higher levels of urinary cortisol than women [3] and these differences arise during childhood [4]. This seems to indicate that men are subjected to higher stress levels and might account for delayed healing and stronger UVinduced immune-suppression. 3. Facial and body hair Hair performs no vital function but its psychological functions are inestimable [5]. Hair follicles populate the entire cutaneous surface, with the exception of palms, soles, glans penis and mucocutaneous junctions. They are formed before birth and no new follicles develop after birth. Hair is morphologically and biologically different in different parts of the body, and varies in structure, rate of growth and response to stimuli. Eyebrows and eyelashes do not respond to sex hormones, whereas pubic, axillary and facial hair, do. Masculinizing syndromes in women commonly produce hirsutism [6], and male beard depends on testicular hormones, as witnessed by the reduction of beard growth upon castration, and by the re-growth of beard in eunuchs treated with androgens [5]. Paramount scientific efforts have been devoted to learning about the growth and loss of scalp and facial hair, particularly to treat androgenic alopecia in men and hirsutism in women. Hirsutism affects 5–15% of Caucasian women and is usually a sign of an endocrine abnormality. Whereas the treatment of androgenic alopecia in men has only met partial success, hirsutism in women can be treated with spironolactone alone or in a drug-combination therapy, together with either mestranol and norethindrone, or dexamethasone. Decreased production rates of testosterone in normal and hirsute women were noted after 1 to few weeks, and reduction in hair growth rate was observed after a few months, followed by a decrease in diameter of the hair shaft [7,8]. 4. Sebum Sebaceous glands are holocrine glands. Their vast majority is connected to hair follicles. On the scalp, forehead, cheeks and chin, their number varies between 400 and 900 per cm2, elsewhere there are less than 100 per cm2. No sebaceous glands are found on the palm or the sole. With androgenic hormonal stimulation, sebaceous glands increase in size and in secretory activity. Sebaceous
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glands consist of lobules of epithelial cells clustered at the extremities of the sebaceous duct. They differentiate in a centripetal manner to become lipid producing cells. As the cells differentiate, they disintegrate into an amorphous mass of lipids and cellular debris (sebum) that is discharged into the sebaceous duct [6] and eventually reaches the surface. Sebum consists of glycerides and free fatty acids (57%), wax esters (26%), squalene (12%), cholesteryl esters (3%) and cholesterol (1.5%) [5]. Men have been reported to have higher sebum production and larger pore size [9]. Caucasian men have been reported to have an average of 3 mg of sebum per square centimeter of skin surface (with large inter-individual variability), whereas Caucasian women have 0.7 mg/cm2 [10]. A Korean study with 30 males and 30 females found a striking positive correlation between male sex, pore size and sebum excretion [11]. Sebum participates in maintaining the flexibility and the extensibility of the stratum corneum and in its waterproofing properties. It also plays a role as a lubricant. Excess sebum is associated with undesirable esthetic phenomena, such as poreenlargement, as well as with pathological phenomena such as acne. 5. Sweat Sweat can be produced by eccrine and apocrine sweat glands. These glands are located in the dermis and produce sweat that is secreted through tiny ducts onto the surface. Sweat from eccrine glands is an odorless, colorless hypotonic solution with pH between 4.5 and 5.5. It contains Sodium and Potassium Chloride, urea, lactate, bicarbonate, ammonia and oligo-elements such as calcium, phosphorous, magnesium, etc. [6]. Sweat is secreted by the three million or so eccrine sweat units, distributed all over the body at birth, and their number does not increase with age. Eccrine sweat units are found everywhere except at the muco-cutaneous junctions. They are highly concentrated in the soles (600 cm 2), palms, axillae and forehead, and less concentrated on the back (60 cm 2) [5]. Apocrine sweat glands are confined in the axillae, areolae, and in the perineal and circum-anal areas [6]. They become functional just before puberty. Since gonadoectomy of adults does not affect apocrine sweat glands functions, hormonal control might be involved only in their maturation but not in the maintaining their function [5]. The apocrine sweat is odorless, milky and viscid. The presence of a secretory opening in common with that of sebaceous glands means that apocrine sweat gland secretions will be mixed with sebum, and this might account for its milky appearance [5]. Subsequent bacterial action is necessary for odor production. Men and women have different micro-flora, which can be influenced by sebum, sweat and pH [12]. A person can perspire up to more than 10 l/day. One liter of evaporated sweat removes about 600 kcal of heat from the body [6]. Males subjected to physical exercise sweat at a larger rate than females (800 ml/h versus 450 ml/h). Correcting for body surface does not suppress the difference, with male sweat rate between 30% and 40% higher than in females [13,14]. The sweating responses to thermal stimulation were measured in 28 men and 18 women aged 70 and over and were compared with the responses in young sex matched controls. Men older than 70 years had a marked reduction in sweating activity in comparison with the controls (average age 35 years) and the body temperature threshold for the onset of sweating was increased by nearly onehalf degree Celsius. The reduced response and elevated threshold were even more pronounced in aged females [15]. 6. Surface pH Sweat and sebum may influence the acidity of the skin. On women’s forearms the pH was found to be about 5.6 0.4 whereas
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in men’s forearm, the pH was found to be 4.6 0.4 [10,16]. Other authors found that on women’s forearm the average pH was 5.54 whereas in men it was 5.80 [17]. This difference could be the consequence of the fact that in Jacobi’s experiment [10], the forearm was washed with water, and the stratum corneum was removed with Tesa film just before the measurements, whereas in Ehlers’ experiment [17], the volunteers were asked not to wash their skin in the 12 h preceding the experiment. Skin pH is assessed by measuring the pH of a determined volume of water extemporaneously deposited on the surface. The measured pH is therefore an indication of protons accumulated outside of skin cells, in the stratum corneum or, when the stratum corneum is stripped off, it is a measure of the free protons accumulated outside basal and supra-basal epidermal cells and in the interstitial fluid. Skin is a very good buffer, and when acids or bases are topically applied, the pH of the surface returns to physiological values within few hours or less. Topical application of weak acids at moderate concentrations in formulas having pH 3–4 has been known to increase the rate of shedding of corneocytes from the outer layer of the stratum corneum. Topical applications of creams with higher pH (8) transiently increase the trans-epidermal water loss (our unpublished observations). The morphological and biochemical consequences of these findings are still the object of research. 7. Skin thickness, collagen and water retention The dermis contains water, ground substance and elastic fibers. These contribute to its thickness. At all ages, men’s skin is thicker [18–20]. The extent of the difference varies with anatomical region. On the forearm it has been reported to be of the order of 20% [19]. After menopause, women’s skin is 10% thinner than before menopause [21]. Skin thickness decreases in men and women, starting at the age of 45 [22]. Other authors report that skin thickness decreases linearly with age in men starting at the age of 20, whereas it seems to remain constant in women until the age of 50 or so, and then starts decreasing [19]. It was also reported that the amount of hydroxyl-proline per square millimeter of skin, obtained upon hydrolysis of defatted and dried biopsies, decreases linearly with age by about 1% per year throughout adult life [19]. The rate of loss is the same in both males and females although total hydroxyl-proline content is smaller in females at all ages. Using the same methodologies, other authors found analogous results [23]. These findings are generally interpreted as indicative of collagen loss with age and some authors consider that skin thinning with age is the consequence of collagen loss. Indeed, a positive correlation was found between levels of hydroxyl-proline and caliper-measured skin thickness [19]. These changes might affect the elasticity, defined as the proportionality factor between the intensity of the stress applied to the skin and its strain [24]. It was also reported that the torsion extensibility (i.e. the strain of the skin subjected to a torque) decreases sharply after the age of 35 [22]. It has to be noted, though, that while hydroxyl-proline content decreases linearly with age in both men and women, skin thickness remains constant in women until the age of 50 or so, in contradiction with what would be expected from the hydroxy-prolyl levels [19]. It has been suggested that the decrease of skin thickness and the loss of hydroxyl-proline be the consequence of the hormonal imbalance associated with menopause. Indeed, the hydroxyl-proline levels in biopsies from women treated for 2–10 years with oestradiol and testosterone was nearly 50% higher than in age-matched untreated postmenopausal women [25]. This is supported by the observation that an ovarectomy is associated with thinning of the skin whereas estrogen therapy thickens skin [26]. A sonography study pointed out that in fertile women the thickness of the skin correlated
positively with the level of sex hormones, as if it were the consequence of hormone-induced water retention in the skin [27]. Topical application of estrogen has been reported to increase skin thickness by nearly 10% as compared with less than 5% for the placebo group [28]. 8. Skin tone Skin color is modulated by melanin, blood and other pigments. Melanin is synthetized in melanocytes, dendritic cells located on the basal layer of the epidermis, each one injecting melanosomes into 24–36 keratinocytes. Melanocytes are differently distributed, varying from 17 8 per mm of histology section on the shoulders, to 12 7 per mm on legs and arms, to 3 2 per mm on the anterior part of the trunk [29]. No gender-linked difference has been reported for melanocyte distribution. Yet, within individual ethnic groups, men have been reported to have darker and less reflective complexions [30–32]. It has been suggested that this is the consequence of men having a more vascularized upper dermis [26] and more melanin [33,34]. These differences could have hormonal causes because they arise during puberty and also increase with age [35]. Men undergo a more intense facultative pigmentation after sun exposure and retain it for longer time than women [36] and women’s skin lightens faster then men’s skin [37]. Radiance and glow are the consequence of surface homogeneity and can be improved by mild exfoliation. The presence of facial hair adds to the darker complexion generally perceived in men. 9. Immune systems and skin cancer Men have a greater susceptibility to bacterial and viral infections [38]. Women are more prone to autoimmune and inflammatory diseases. Rheumatoid arthritis is four times more common in women [39,40] and systemic lupus is nine times more common in women [41]. Men are more prone to skin cancer, with squamous cell carcinomas being twice more common in older men [42]. Men are prone to greater UV-induced immune-suppression [43]. The prevalence of melanoma is 1.72% in men and only 1.22% in women [44]. In 60–79-year age group men are twice as likely to develop melanoma. The rate of death from melanoma in the USA between 1973 and 1997 was 2-fold higher in men compared to women [41]. A possible explanation for the differences in cancer incidence and prevalence in men is the UV- and stress-induced immunesuppression in human skin. Solar irradiation can cause a variety of damage to skin and one that has been reported is the inhibition of contact hypersensitivity or delayed type hypersensitivity [43]. Psychological stress has also been shown to impair the immune response associated with contact hypersensitivity and delayedtype hypersensitivity [45,46] and the high level of urinary cortisol found in men might be an indicator of higher psychological stress in men. These two factors might concur into accounting for the greater occurrence of skin cancer in men. 10. Healing and other surface properties Re-epithelialization is the covering by keratinocytes of an area devoid of epithelium because of mechanical or burn-induced ablation, and to achieve cellular multiplication and differentiation to generate a functional stratum corneum. Men have slower healing rates than women at all ages. Androgens are believed to be causally related to this phenomenon [47,48]. The epidermis contains about 9.3 million cells per cm2, of which 7.5 million nucleated cells, 140,000 Langerhans cells, 200,000 melanocytes, and 1.8 million corneocytes with an average surface of 900 mm2 per corneocyte [49]. The number of layers in the
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stratum corneum changes with anatomical site. There are 6 2 layers in the genital area, 12 2 in the scalp and on the trunk, 15 4 in the extremities, 47 24 on the soles and 86 36 layers on the heels. There is no gender-linked difference, with the exception of a slight increase of stratum corneum thickness with age in male skin on the cheeks and on the back [50]. There is no difference between men and women for epidermal phenomena such as the daily shedding of the outer sheet of the stratum corneum [10], or in transepidermal water loss [10], or in the so-called permeability barrier function [51]. 11. Skin sensorial properties The epidermis harbors sensory nerve endings which sense and transmit heat, pain, itch, etc. The skin contains Merkel cells and neural endings coated with Schwann cells. These cells detect stretch and shear occurring on the skin, and are equipped with temperature-sensitive receptors. Men and women have different tactile and sensorial perception. Men have less sensitivity to pain and temperature extremes [52–54] whereas women are less sensitive to cold [55]. Mast cells can release histamine that triggers pain and itch. There is no gender-linked difference in the density and distribution of mast cells in the skin. Their number increases with age (10–20%), except on proximal extremities [56]. Older age and male sex are associated with a stronger response to histamine [57]. The wheal and flare (swelling and reddening) responses to histamine are linearly related to dose over a wide range of concentrations. In summer, wheal responses are smaller, probably due to increased thickness of the epidermis. Female subjects generally express larger wheal responses than males [58]. 12. Muscular mass and body fat Men have larger lean body mass and less fat [59,60]. In both genders the muscle mass decreases with age [59,61,62]. This contributes to the exterior aspect of the face and of body. The rate of muscular protein synthesis is identical in young women and in young men, and becomes 30% smaller in elderly women [63]. Larger muscle mass and higher rates of protein synthesis have long been attributed to higher levels of testosterone, yet, the reduction of muscular protein synthesis observed in the elderly cannot be restored by treatment with 5 mg/day testosterone or with 75 mg/ day de-hydro-epi-androsterone for 1 year [64]. Energy intake and energy expenditure, the control of appetite and metabolism and the potential accumulation of fat are regulated by leptin. Serum levels of leptin in fasting women are higher than in men (16 11 ng/ml versus 3 1.5 ng/ml). In males and females of comparable body fat ratio, serum leptin was higher in females than in males (13 8 ng/ml versus 3 1.7 ng/ml). Serum leptin correlates positively with bio-available estrogen in postmenopausal women, and negatively with total or bio-available testosterone in men [65]. Cathecolamine-mediated release of free fatty acid from the leg and free fatty acid release from subcutaneous tissue in the upper body and fat oxidation rate are larger in men than in women [66]. Fat oxidation at rest is also larger in men (88 mm/min versus 51 mm/min) [67]. A major contributor to the skin’s appearance is the amount of subcutaneous fat. Women store more fat in the gluteal-femoral region, whereas men store more fat in the visceral depot. Women have larger amounts of subcutaneous fat than men [68]. Among160 young individuals of African or Caucasian ethnicity of both sexes boys had larger waist circumference and visceral adipose tissue than girls with the same body mass index [69]. The anthropometric analysis of a group of 1884 Chinese adults (age 20–
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40) confirmed that males have larger body mass index, waist circumference, hip circumference, waist-to-hip ratio and conicity index than females. Conicity is an index of body fat distribution expressing an individual’s waist circumference relative to the circumference of a cylinder generated with that persons weight and height assuming constant body density. This study confirmed that females had larger absolute and relative total body fat than males [70]. The difference in muscle mass and body fat contributes to the visual differences between men and women. With age, muscular atrophy or modifications of subcutaneous adipose tissue play an important role in the facial characteristics of men and women, as in the specific distribution of peri-oral wrinkles and sagging chin in elderly women, versus deep expression wrinkles which are more common in aging men. This contributes to the perceived age of men and women, albeit in a non-dramatic fashion, as shown in studies where men have been found to appear 0.37 years older than their age and women 0.54 years younger [71]. 13. Cosmetic and dermatological implications based on gender differences in skin Understanding gender-linked differences in skin physiology can help improving cosmetic treatments for anti-aging care via prevention, repair and protection, as well as to achieve skin smoothness, clarity and overall health. Some of the physiological differences between male and female skin can be ascribed to different levels of sex and stress hormones. This might lead for instance, to cosmetic interventions and dermatological treatments by modulating their binding to receptors in the skin and not in other body organs, e.g. to act on hair growth and on water retention. Facial and body hair have tremendous cultural, psychological and behavioral effects and it might be desirable to modulate their rate of growth and their response to stimuli. Facial hair removal is performed differently by women and men, and one might wonder whether shaving promotes helpful or harmful exfoliation or if it adds to one’s proneness to irritation or inflammation. Indeed, the presence of hair makes man’s facial skin much more penetrable by xenobiotics than women’s skin, and the shaving-associated exfoliation plays perhaps a very minor role in their penetration. Learning about this might lead to better pre- and post-shave treatments, as well as to a completely new approach to ease the discomfort sometimes associated with shaving, such as redness, dryness, ingrown hairs and hyper-reactivity. Appropriate sebum control by modulating the binding of sex hormones to receptors in sebaceous glands could be used to control pore size, which is known to be larger in men. Further understanding sebum’s role in and on skin can have implications in treating excess oil, acne, and the clogging of pores. Sebum and sweat might be relevant to the differences between male and female skin’s micro-flora and biochemical properties. Understanding male perspiration, its role in cooling the body, its social stigma, may result in better gender-specific cosmetic preparations. Learning about the response of skin’s micro-flora to both sebum and sweat in males may contribute to new approaches in controlling perspiration and in modulating micro-flora-driven olfactory phenomena. The different level of sebum/sweat on the surface of the skin might influence the way men perceive the sensations associated to the topical application of products. Indeed men and women appear to have different tactile and sensory perceptions as well as tolerances on skin. Awareness of this will certainly have implications in the hedonics of a formulation, which will have to take into account the rates of absorption and of penetration, as well as the residual after-feel, and will have to be appropriate for
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the environmental conditions, for the climate as well as for the age of the consumer. Melanin and hemoglobin contribute to overall complexion. New treatments for skin redness, broken capillaries, and rosacea will benefit from future learning about micro-circulatory properties and control of melanin synthesis. The study of UVA and UVB protection in men’s more cancer-prone skin can be further fostered. As a matter of fact, tan does not provide significant skin protection against solar radiation to Caucasian, and Caucasian men are more susceptible to ultraviolet-induced immune-suppression and skin cancer than women. Moreover, men seem to be more prone to psychological stress and therefore their skin’s immune system is under harsher attack. Men must be therefore more diligent with sun protection, and use sunscreen more frequently than women. Paramount progress could be made in cosmetics and dermatology by learning about the impairment of dendritic cells by neurotransmitters and their effects on skin immunity. References [1] Chen W, Thiboutot D, Zouloulis C. Cutaneos androgens metabolism: basic research and clinical perspectives. J Invest Dermatol 2002;119:992–1007. [2] Thiboutot D, Jabara S, McAllister J, Sivarajah A, Gilliland K, Cong Z, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and in immortalized sebocyte cell line (SEB-1). J Invest Dermatol 2003;120:905–14. [3] Raven P, Taylor N. Sex differences in the human metabolism of cortisol. Endocr Res 1996;22:751–5. [4] Wudy S, Hartmann M, Remer T. Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth. Am J Physiol Endrocr Metab 2007;293:E970–6. [5] Fitzpatrick TB, Zur Eisen A, Wolff K, Freedberg IM, Austen KF. Dermatology in general medicine. New York: McGraw-Hill; 1987. [6] Moschella SL, Hurley HG. Dermatology. Philadelphia: WB Saunders Company; 1985. [7] Boisselle A, Tremblay RR. New therapeutic approach to the hirsute patient. Fertil Steril 1979;32:276–9. [8] Pittaway DE, Maxson WS, Wentz AC. Spironolactone in combination drug therapy for unresponsive hirsutism. Fertil Steril 1985;43:878–82. [9] Pochi P, Strauss J. Endocrinologic control of the development and activity of the human sebaceous gland. J Invest Dermatol 1974;62:191–201. [10] Jacobi U, Gautier J, Sterry W, Ladermann J. Gender-related differences in the physiology of the Stratum Corneum. Dermatology 2005;211:312–7. [11] Roh M, Han M, Kim D, Chung K. Sebum output as a factor contributing to the size of facial pores. Br J Dermatol vol 2006;155:890–4. [12] Marples R. Sex, constancy, and skin bacteria. Arch Dermatol Res 1982;272:317–20. [13] Green JM, Bishop PA, Muir IH, Lomax RG. Gender difference in sweat lactate. Eur J Appl Physiol 2000;82:230–5. [14] Yosipovitch G, Reis J, Tur E, Sprecher E, Yarnitsky D, Boner G. Sweat secretion, stratum corneum hydration, small nerve function and pruritus in patients with advanced chronic renal failure. Br J Dermatol 1995;133:561–4. [15] Foster KG, Ellis FP, Dore´ C, Exton-Smith AN, Weiner JS. Sweat responses in the aged. Age Ageing 1976;5:91–101. [16] Ohman H, Vahlquist A. In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis. Acta Derm-Venereol 1994;74:375–9. [17] Ehlers C, Ivens UI, Møller ML, Senderowitz T, Serup J. Females have lower skin surface pH than men. Skin Res Technol 2001;7:90–4. [18] Seidenari L, Smith U, Krotkiewski M, Bjorntorp P. Cellularity in different regions of adipose tissue in young men and women. Metabolism 1972;21: 1143–53. [19] Shuster S, Black M, McVitie E. The influence of age and sex on skin thickness, skin collagen and density. Br J Dermatol 1975;93:639–43. [20] Sandby-Moller J, Poulsen T, Wulf H. Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits. Acta Derm-Venerol 2003;83:41–3. [21] Panyakhamlerd K, Chotnopparattara P, Taechakraichana N, Kukulprasong A, Chaikittisilpa S, Limpaphayom K. Skin thickness in different menopausal status. J Med Assoc Thai 1999;82:352–6. [22] Leveque JL, Corcuff P, de Rigal J, Agache P. In vivo studies of the evolution of physical properties of the human skin with age. Int J Dermatol 1984;23: 322–9. [23] Brincat M, Kabalan S, Studd JWW, Moniz CF, De Trafford J, Montgomery J. A study of the decrease of skin collagen content, skin thickness and bone mass in the post menopausal woman. Obstetr Gynecol 1987;70:840–5. [24] Alexander H, Cook T. Variations with age in the mechanical properties of human skin in vivo. J Tissue Viability 2006;16:6–11. [25] Brincat M, Moniz CF, Studd JW, Darby AJ, Magos A, Cooper D. Sex hormones and skin collagen content in post-menopausal women. Br Med J 1983;287: 1337–8.
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Sex hormones and glucocorticoids: interactions with the immune system. Ann NY Acad Sci 1999;876:102–17. [41] Dao H, Kazin R. Gender differences in skin: a review of the literature. Gender Med 2007;4:308–28. [42] Dal H, Boldemann C, Lindelo¨f B. Trends during a half century in relative squamous cell carcinoma distribution by body site in the Swedish population: support for accumulated sun exposure as the main risk factor. J Dermatol 2008;35:55–362. [43] Damian DL, Patterson CR, Stapelberg M, Park J, Barnetson RS, Halliday GM. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J Invest Dermatol 2008;128:447–54. [44] Lasithiotakis K, Leiter U, Meier F, Eigentler T, Metzler G, Moehrle M, et al. Age and gender are significant independent predictors of survival in primary cutaneous melanoma. Cancer 2008;112:1795–804. [45] Streilein J, Taylor J, Vincek V. Relationship between ultraviolet radiationinduced immune-suppression and carcinogenesis. J Invest Dermatol 1994;103:S107–11. [46] Poon SC, Barnetson RS, Halliday GM. Prevention of immune-suppression by sunscreens in humans is unrelated to protection from erythema and dependent on protection from ultraviolet A in the face of constant UVB protection. J Invest Dermatol 2003;121:184–90. [47] Gilliver SC, Ruckshanthi JP, Hardman MJ, Zeef LA, Ashcroft GS. 5a-Dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization. J Pathol 2009;217:73–82. [48] Gilliver SC, Ashworth JJ, Ashcroft GS. The hormonal regulation of cutaneous wound healing. Clin Dermatol 2007;25:56–62. [49] Hoath SB, Leahy DG. The organization of human epidermis: functional epidermal units and phi proportionality. J Invest Dermatol 2003;121:1440–6. [50] Ya-Xian Z, Suetake T, Tagami H. Number of cell layers of the stratum corneum in normal skin—relationship to the anatomical location on the body, age, sex, and physical parameters. Arch Dermatol Res 1999;291:555–9. [51] Reed JT, Ghadially R, Elias PM. Skin type, but neither race nor gender, influence epidermal permeability barrier function. Arch Dermatol 1995;131:1134–8. [52] Meh D, Denislic M. Quantitative assessment of thermal and pain sensitivity. J Neurol Sci 1994;127:164–9. [53] Procacci P, Bozza G, Buzzelli G. The cutaneous pricking pain threshold in old age. Gerontol Clin 1970;12:213–8. [54] Weinstein S, Sersen E. Tactual sensitivity as a function of handedness and laterality. J Comp Physiol Psychol 1961;54:665–9. [55] Sato H, Yamasaki K, Yasukouchi A, Watanuki S, Iwanaga K. Sex differences in human thermoregulatory response to cold. J Hum Ergol (Tokyo) 1988;17: 57–65. [56] Weber A, Knop J, Mauer M. Pattern analysis of human cutaneous mast cell population by total body surface mapping. Br J Dermatol 2003;148:224–8. [57] Bordignon V, Burastero SE. Age, gender and reactivity to allergens independently influence skin reactivity to histamine. J Investig Allergol Clin Immunol 2006;16:129–35. 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Contents lists available at ScienceDirect
Journal of Dermatological Science journal homepage: www.intl.elsevierhealth.com/journals/jods
Review article
Gender-linked differences in human skin Paolo U. Giacomoni a,b,*, Thomas Mammone a,b, Matthew Teri b a b
Clinique Laboratories, Melville, NY, United States Estee Lauder Companies, New York, NY, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 27 April 2009 Received in revised form 11 May 2009 Accepted 2 June 2009
Background: The physiology of body organs can be affected by gender. Skin and skin appendages are influenced by sex hormones. Objective: This review work has been undertaken to point out the most conspicuous physiological differences observed between men’s and women’s skin. Methods: The literature has been searched and relevant results have been gathered. Results: Men’s and women’s skins differ in hormone metabolism, hair growth, sweat rate, sebum production, surface pH, fat accumulation, serum leptins, etc. Examples of differences in the proneness to cutaneous diseases and skin cancer are quoted. Conclusion: The knowledge of gender-linked cutaneous differences might help in preparing malespecific products for more appropriate dermatological treatments or cosmetic interventions. ß 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Human skin Gender-linked differences Physiology Aging
Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hormones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Facial and body hair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sebum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sweat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Surface pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin thickness, collagen and water retention . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin tone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Immune systems and skin cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Healing and other surface properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin sensorial properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Muscular mass and body fat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cosmetic and dermatological implications based on gender differences in skin References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Gender-linked physiological differences have been pointed out in body organs of healthy and diseased subjects, comprising the skin. The skin controls the gaseous exchanges with the exterior, regulates the thermal equilibrium of the body, contains sensory organs to interact with the environment, harbors saprofite microflora, provides a physical barrier against the penetration of
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inorganic matter, and a biochemical defense against viruses and other pathogens. It also provides a cushion against traumatisms and is equipped with dendritic cells to trigger immune responses. This review summarizes anatomical, physiological and biochemical differences between male and female skin (summarized in Table 1) and discusses how this knowledge may contribute to the improvement of skin care interventions, particularly for men. 2. Hormones
* Corresponding author at: Clinique Laboratories, 125 Pinelawn Road, Melville, NY 11747, United States. Tel.: +1 631 531 1238. E-mail address: [email protected] (P.U. Giacomoni).
Men and women skin differ in the metabolism of sex hormones, and in the response to them [1]. Testosterone is synthesized in the testes, in the ovaries and in the adrenal cortex. It is converted to
0923-1811/$36.00 ß 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jdermsci.2009.06.001
P.U. Giacomoni et al. / Journal of Dermatological Science 55 (2009) 144–149 Table 1 Gender-linked differences in human skin. Characteristics
Males
Females
Ref.
Sweat rate during exercise (ml/h) Sebum (mg/cm2) pH (surface) pH (intra-epidermal) Leptin (serum level, ng/ml) Skin thickness (ratio men/women) SCC (incidence ratio men/women) Systemic lupus (incidence ratio men/women) Melanoma (mortality ratio men/women)
800 3 5.8 4.6 16
450 0.7 5.5 5.6 3
[6] [10] [17] [10] [65] [19] [42] [41] [41]
1.2 2 0.11 2
de-hydro-testosterone by 5-a-reductase. Estrogen and progesterone are synthesized in the ovaries. Present at birth, their levels increase during adolescence and their quantitative difference determines the secondary sexual characteristics of the individual. Skin is a steroidogenic tissue: it metabolizes sex hormones and responds to them [2]. Aromatase converts testosterone to estradiol in women’s skin, where excess testoserone can lead to androgenic-dependent alopecia or to hirsutism. In men, beard growth and male-pattern hair loss are abolished when testosterone is removed [1]. A sexual dimorphism has been pointed out also in the levels of non-sexual hormones. Men have higher levels of urinary cortisol than women [3] and these differences arise during childhood [4]. This seems to indicate that men are subjected to higher stress levels and might account for delayed healing and stronger UVinduced immune-suppression. 3. Facial and body hair Hair performs no vital function but its psychological functions are inestimable [5]. Hair follicles populate the entire cutaneous surface, with the exception of palms, soles, glans penis and mucocutaneous junctions. They are formed before birth and no new follicles develop after birth. Hair is morphologically and biologically different in different parts of the body, and varies in structure, rate of growth and response to stimuli. Eyebrows and eyelashes do not respond to sex hormones, whereas pubic, axillary and facial hair, do. Masculinizing syndromes in women commonly produce hirsutism [6], and male beard depends on testicular hormones, as witnessed by the reduction of beard growth upon castration, and by the re-growth of beard in eunuchs treated with androgens [5]. Paramount scientific efforts have been devoted to learning about the growth and loss of scalp and facial hair, particularly to treat androgenic alopecia in men and hirsutism in women. Hirsutism affects 5–15% of Caucasian women and is usually a sign of an endocrine abnormality. Whereas the treatment of androgenic alopecia in men has only met partial success, hirsutism in women can be treated with spironolactone alone or in a drug-combination therapy, together with either mestranol and norethindrone, or dexamethasone. Decreased production rates of testosterone in normal and hirsute women were noted after 1 to few weeks, and reduction in hair growth rate was observed after a few months, followed by a decrease in diameter of the hair shaft [7,8]. 4. Sebum Sebaceous glands are holocrine glands. Their vast majority is connected to hair follicles. On the scalp, forehead, cheeks and chin, their number varies between 400 and 900 per cm2, elsewhere there are less than 100 per cm2. No sebaceous glands are found on the palm or the sole. With androgenic hormonal stimulation, sebaceous glands increase in size and in secretory activity. Sebaceous
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glands consist of lobules of epithelial cells clustered at the extremities of the sebaceous duct. They differentiate in a centripetal manner to become lipid producing cells. As the cells differentiate, they disintegrate into an amorphous mass of lipids and cellular debris (sebum) that is discharged into the sebaceous duct [6] and eventually reaches the surface. Sebum consists of glycerides and free fatty acids (57%), wax esters (26%), squalene (12%), cholesteryl esters (3%) and cholesterol (1.5%) [5]. Men have been reported to have higher sebum production and larger pore size [9]. Caucasian men have been reported to have an average of 3 mg of sebum per square centimeter of skin surface (with large inter-individual variability), whereas Caucasian women have 0.7 mg/cm2 [10]. A Korean study with 30 males and 30 females found a striking positive correlation between male sex, pore size and sebum excretion [11]. Sebum participates in maintaining the flexibility and the extensibility of the stratum corneum and in its waterproofing properties. It also plays a role as a lubricant. Excess sebum is associated with undesirable esthetic phenomena, such as poreenlargement, as well as with pathological phenomena such as acne. 5. Sweat Sweat can be produced by eccrine and apocrine sweat glands. These glands are located in the dermis and produce sweat that is secreted through tiny ducts onto the surface. Sweat from eccrine glands is an odorless, colorless hypotonic solution with pH between 4.5 and 5.5. It contains Sodium and Potassium Chloride, urea, lactate, bicarbonate, ammonia and oligo-elements such as calcium, phosphorous, magnesium, etc. [6]. Sweat is secreted by the three million or so eccrine sweat units, distributed all over the body at birth, and their number does not increase with age. Eccrine sweat units are found everywhere except at the muco-cutaneous junctions. They are highly concentrated in the soles (600 cm 2), palms, axillae and forehead, and less concentrated on the back (60 cm 2) [5]. Apocrine sweat glands are confined in the axillae, areolae, and in the perineal and circum-anal areas [6]. They become functional just before puberty. Since gonadoectomy of adults does not affect apocrine sweat glands functions, hormonal control might be involved only in their maturation but not in the maintaining their function [5]. The apocrine sweat is odorless, milky and viscid. The presence of a secretory opening in common with that of sebaceous glands means that apocrine sweat gland secretions will be mixed with sebum, and this might account for its milky appearance [5]. Subsequent bacterial action is necessary for odor production. Men and women have different micro-flora, which can be influenced by sebum, sweat and pH [12]. A person can perspire up to more than 10 l/day. One liter of evaporated sweat removes about 600 kcal of heat from the body [6]. Males subjected to physical exercise sweat at a larger rate than females (800 ml/h versus 450 ml/h). Correcting for body surface does not suppress the difference, with male sweat rate between 30% and 40% higher than in females [13,14]. The sweating responses to thermal stimulation were measured in 28 men and 18 women aged 70 and over and were compared with the responses in young sex matched controls. Men older than 70 years had a marked reduction in sweating activity in comparison with the controls (average age 35 years) and the body temperature threshold for the onset of sweating was increased by nearly onehalf degree Celsius. The reduced response and elevated threshold were even more pronounced in aged females [15]. 6. Surface pH Sweat and sebum may influence the acidity of the skin. On women’s forearms the pH was found to be about 5.6 0.4 whereas
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in men’s forearm, the pH was found to be 4.6 0.4 [10,16]. Other authors found that on women’s forearm the average pH was 5.54 whereas in men it was 5.80 [17]. This difference could be the consequence of the fact that in Jacobi’s experiment [10], the forearm was washed with water, and the stratum corneum was removed with Tesa film just before the measurements, whereas in Ehlers’ experiment [17], the volunteers were asked not to wash their skin in the 12 h preceding the experiment. Skin pH is assessed by measuring the pH of a determined volume of water extemporaneously deposited on the surface. The measured pH is therefore an indication of protons accumulated outside of skin cells, in the stratum corneum or, when the stratum corneum is stripped off, it is a measure of the free protons accumulated outside basal and supra-basal epidermal cells and in the interstitial fluid. Skin is a very good buffer, and when acids or bases are topically applied, the pH of the surface returns to physiological values within few hours or less. Topical application of weak acids at moderate concentrations in formulas having pH 3–4 has been known to increase the rate of shedding of corneocytes from the outer layer of the stratum corneum. Topical applications of creams with higher pH (8) transiently increase the trans-epidermal water loss (our unpublished observations). The morphological and biochemical consequences of these findings are still the object of research. 7. Skin thickness, collagen and water retention The dermis contains water, ground substance and elastic fibers. These contribute to its thickness. At all ages, men’s skin is thicker [18–20]. The extent of the difference varies with anatomical region. On the forearm it has been reported to be of the order of 20% [19]. After menopause, women’s skin is 10% thinner than before menopause [21]. Skin thickness decreases in men and women, starting at the age of 45 [22]. Other authors report that skin thickness decreases linearly with age in men starting at the age of 20, whereas it seems to remain constant in women until the age of 50 or so, and then starts decreasing [19]. It was also reported that the amount of hydroxyl-proline per square millimeter of skin, obtained upon hydrolysis of defatted and dried biopsies, decreases linearly with age by about 1% per year throughout adult life [19]. The rate of loss is the same in both males and females although total hydroxyl-proline content is smaller in females at all ages. Using the same methodologies, other authors found analogous results [23]. These findings are generally interpreted as indicative of collagen loss with age and some authors consider that skin thinning with age is the consequence of collagen loss. Indeed, a positive correlation was found between levels of hydroxyl-proline and caliper-measured skin thickness [19]. These changes might affect the elasticity, defined as the proportionality factor between the intensity of the stress applied to the skin and its strain [24]. It was also reported that the torsion extensibility (i.e. the strain of the skin subjected to a torque) decreases sharply after the age of 35 [22]. It has to be noted, though, that while hydroxyl-proline content decreases linearly with age in both men and women, skin thickness remains constant in women until the age of 50 or so, in contradiction with what would be expected from the hydroxy-prolyl levels [19]. It has been suggested that the decrease of skin thickness and the loss of hydroxyl-proline be the consequence of the hormonal imbalance associated with menopause. Indeed, the hydroxyl-proline levels in biopsies from women treated for 2–10 years with oestradiol and testosterone was nearly 50% higher than in age-matched untreated postmenopausal women [25]. This is supported by the observation that an ovarectomy is associated with thinning of the skin whereas estrogen therapy thickens skin [26]. A sonography study pointed out that in fertile women the thickness of the skin correlated
positively with the level of sex hormones, as if it were the consequence of hormone-induced water retention in the skin [27]. Topical application of estrogen has been reported to increase skin thickness by nearly 10% as compared with less than 5% for the placebo group [28]. 8. Skin tone Skin color is modulated by melanin, blood and other pigments. Melanin is synthetized in melanocytes, dendritic cells located on the basal layer of the epidermis, each one injecting melanosomes into 24–36 keratinocytes. Melanocytes are differently distributed, varying from 17 8 per mm of histology section on the shoulders, to 12 7 per mm on legs and arms, to 3 2 per mm on the anterior part of the trunk [29]. No gender-linked difference has been reported for melanocyte distribution. Yet, within individual ethnic groups, men have been reported to have darker and less reflective complexions [30–32]. It has been suggested that this is the consequence of men having a more vascularized upper dermis [26] and more melanin [33,34]. These differences could have hormonal causes because they arise during puberty and also increase with age [35]. Men undergo a more intense facultative pigmentation after sun exposure and retain it for longer time than women [36] and women’s skin lightens faster then men’s skin [37]. Radiance and glow are the consequence of surface homogeneity and can be improved by mild exfoliation. The presence of facial hair adds to the darker complexion generally perceived in men. 9. Immune systems and skin cancer Men have a greater susceptibility to bacterial and viral infections [38]. Women are more prone to autoimmune and inflammatory diseases. Rheumatoid arthritis is four times more common in women [39,40] and systemic lupus is nine times more common in women [41]. Men are more prone to skin cancer, with squamous cell carcinomas being twice more common in older men [42]. Men are prone to greater UV-induced immune-suppression [43]. The prevalence of melanoma is 1.72% in men and only 1.22% in women [44]. In 60–79-year age group men are twice as likely to develop melanoma. The rate of death from melanoma in the USA between 1973 and 1997 was 2-fold higher in men compared to women [41]. A possible explanation for the differences in cancer incidence and prevalence in men is the UV- and stress-induced immunesuppression in human skin. Solar irradiation can cause a variety of damage to skin and one that has been reported is the inhibition of contact hypersensitivity or delayed type hypersensitivity [43]. Psychological stress has also been shown to impair the immune response associated with contact hypersensitivity and delayedtype hypersensitivity [45,46] and the high level of urinary cortisol found in men might be an indicator of higher psychological stress in men. These two factors might concur into accounting for the greater occurrence of skin cancer in men. 10. Healing and other surface properties Re-epithelialization is the covering by keratinocytes of an area devoid of epithelium because of mechanical or burn-induced ablation, and to achieve cellular multiplication and differentiation to generate a functional stratum corneum. Men have slower healing rates than women at all ages. Androgens are believed to be causally related to this phenomenon [47,48]. The epidermis contains about 9.3 million cells per cm2, of which 7.5 million nucleated cells, 140,000 Langerhans cells, 200,000 melanocytes, and 1.8 million corneocytes with an average surface of 900 mm2 per corneocyte [49]. The number of layers in the
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stratum corneum changes with anatomical site. There are 6 2 layers in the genital area, 12 2 in the scalp and on the trunk, 15 4 in the extremities, 47 24 on the soles and 86 36 layers on the heels. There is no gender-linked difference, with the exception of a slight increase of stratum corneum thickness with age in male skin on the cheeks and on the back [50]. There is no difference between men and women for epidermal phenomena such as the daily shedding of the outer sheet of the stratum corneum [10], or in transepidermal water loss [10], or in the so-called permeability barrier function [51]. 11. Skin sensorial properties The epidermis harbors sensory nerve endings which sense and transmit heat, pain, itch, etc. The skin contains Merkel cells and neural endings coated with Schwann cells. These cells detect stretch and shear occurring on the skin, and are equipped with temperature-sensitive receptors. Men and women have different tactile and sensorial perception. Men have less sensitivity to pain and temperature extremes [52–54] whereas women are less sensitive to cold [55]. Mast cells can release histamine that triggers pain and itch. There is no gender-linked difference in the density and distribution of mast cells in the skin. Their number increases with age (10–20%), except on proximal extremities [56]. Older age and male sex are associated with a stronger response to histamine [57]. The wheal and flare (swelling and reddening) responses to histamine are linearly related to dose over a wide range of concentrations. In summer, wheal responses are smaller, probably due to increased thickness of the epidermis. Female subjects generally express larger wheal responses than males [58]. 12. Muscular mass and body fat Men have larger lean body mass and less fat [59,60]. In both genders the muscle mass decreases with age [59,61,62]. This contributes to the exterior aspect of the face and of body. The rate of muscular protein synthesis is identical in young women and in young men, and becomes 30% smaller in elderly women [63]. Larger muscle mass and higher rates of protein synthesis have long been attributed to higher levels of testosterone, yet, the reduction of muscular protein synthesis observed in the elderly cannot be restored by treatment with 5 mg/day testosterone or with 75 mg/ day de-hydro-epi-androsterone for 1 year [64]. Energy intake and energy expenditure, the control of appetite and metabolism and the potential accumulation of fat are regulated by leptin. Serum levels of leptin in fasting women are higher than in men (16 11 ng/ml versus 3 1.5 ng/ml). In males and females of comparable body fat ratio, serum leptin was higher in females than in males (13 8 ng/ml versus 3 1.7 ng/ml). Serum leptin correlates positively with bio-available estrogen in postmenopausal women, and negatively with total or bio-available testosterone in men [65]. Cathecolamine-mediated release of free fatty acid from the leg and free fatty acid release from subcutaneous tissue in the upper body and fat oxidation rate are larger in men than in women [66]. Fat oxidation at rest is also larger in men (88 mm/min versus 51 mm/min) [67]. A major contributor to the skin’s appearance is the amount of subcutaneous fat. Women store more fat in the gluteal-femoral region, whereas men store more fat in the visceral depot. Women have larger amounts of subcutaneous fat than men [68]. Among160 young individuals of African or Caucasian ethnicity of both sexes boys had larger waist circumference and visceral adipose tissue than girls with the same body mass index [69]. The anthropometric analysis of a group of 1884 Chinese adults (age 20–
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40) confirmed that males have larger body mass index, waist circumference, hip circumference, waist-to-hip ratio and conicity index than females. Conicity is an index of body fat distribution expressing an individual’s waist circumference relative to the circumference of a cylinder generated with that persons weight and height assuming constant body density. This study confirmed that females had larger absolute and relative total body fat than males [70]. The difference in muscle mass and body fat contributes to the visual differences between men and women. With age, muscular atrophy or modifications of subcutaneous adipose tissue play an important role in the facial characteristics of men and women, as in the specific distribution of peri-oral wrinkles and sagging chin in elderly women, versus deep expression wrinkles which are more common in aging men. This contributes to the perceived age of men and women, albeit in a non-dramatic fashion, as shown in studies where men have been found to appear 0.37 years older than their age and women 0.54 years younger [71]. 13. Cosmetic and dermatological implications based on gender differences in skin Understanding gender-linked differences in skin physiology can help improving cosmetic treatments for anti-aging care via prevention, repair and protection, as well as to achieve skin smoothness, clarity and overall health. Some of the physiological differences between male and female skin can be ascribed to different levels of sex and stress hormones. This might lead for instance, to cosmetic interventions and dermatological treatments by modulating their binding to receptors in the skin and not in other body organs, e.g. to act on hair growth and on water retention. Facial and body hair have tremendous cultural, psychological and behavioral effects and it might be desirable to modulate their rate of growth and their response to stimuli. Facial hair removal is performed differently by women and men, and one might wonder whether shaving promotes helpful or harmful exfoliation or if it adds to one’s proneness to irritation or inflammation. Indeed, the presence of hair makes man’s facial skin much more penetrable by xenobiotics than women’s skin, and the shaving-associated exfoliation plays perhaps a very minor role in their penetration. Learning about this might lead to better pre- and post-shave treatments, as well as to a completely new approach to ease the discomfort sometimes associated with shaving, such as redness, dryness, ingrown hairs and hyper-reactivity. Appropriate sebum control by modulating the binding of sex hormones to receptors in sebaceous glands could be used to control pore size, which is known to be larger in men. Further understanding sebum’s role in and on skin can have implications in treating excess oil, acne, and the clogging of pores. Sebum and sweat might be relevant to the differences between male and female skin’s micro-flora and biochemical properties. Understanding male perspiration, its role in cooling the body, its social stigma, may result in better gender-specific cosmetic preparations. Learning about the response of skin’s micro-flora to both sebum and sweat in males may contribute to new approaches in controlling perspiration and in modulating micro-flora-driven olfactory phenomena. The different level of sebum/sweat on the surface of the skin might influence the way men perceive the sensations associated to the topical application of products. Indeed men and women appear to have different tactile and sensory perceptions as well as tolerances on skin. Awareness of this will certainly have implications in the hedonics of a formulation, which will have to take into account the rates of absorption and of penetration, as well as the residual after-feel, and will have to be appropriate for
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the environmental conditions, for the climate as well as for the age of the consumer. Melanin and hemoglobin contribute to overall complexion. New treatments for skin redness, broken capillaries, and rosacea will benefit from future learning about micro-circulatory properties and control of melanin synthesis. The study of UVA and UVB protection in men’s more cancer-prone skin can be further fostered. As a matter of fact, tan does not provide significant skin protection against solar radiation to Caucasian, and Caucasian men are more susceptible to ultraviolet-induced immune-suppression and skin cancer than women. Moreover, men seem to be more prone to psychological stress and therefore their skin’s immune system is under harsher attack. Men must be therefore more diligent with sun protection, and use sunscreen more frequently than women. Paramount progress could be made in cosmetics and dermatology by learning about the impairment of dendritic cells by neurotransmitters and their effects on skin immunity. References [1] Chen W, Thiboutot D, Zouloulis C. Cutaneos androgens metabolism: basic research and clinical perspectives. J Invest Dermatol 2002;119:992–1007. [2] Thiboutot D, Jabara S, McAllister J, Sivarajah A, Gilliland K, Cong Z, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and in immortalized sebocyte cell line (SEB-1). J Invest Dermatol 2003;120:905–14. [3] Raven P, Taylor N. Sex differences in the human metabolism of cortisol. Endocr Res 1996;22:751–5. [4] Wudy S, Hartmann M, Remer T. Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth. Am J Physiol Endrocr Metab 2007;293:E970–6. [5] Fitzpatrick TB, Zur Eisen A, Wolff K, Freedberg IM, Austen KF. Dermatology in general medicine. New York: McGraw-Hill; 1987. [6] Moschella SL, Hurley HG. Dermatology. Philadelphia: WB Saunders Company; 1985. [7] Boisselle A, Tremblay RR. New therapeutic approach to the hirsute patient. Fertil Steril 1979;32:276–9. [8] Pittaway DE, Maxson WS, Wentz AC. Spironolactone in combination drug therapy for unresponsive hirsutism. Fertil Steril 1985;43:878–82. [9] Pochi P, Strauss J. Endocrinologic control of the development and activity of the human sebaceous gland. J Invest Dermatol 1974;62:191–201. [10] Jacobi U, Gautier J, Sterry W, Ladermann J. Gender-related differences in the physiology of the Stratum Corneum. Dermatology 2005;211:312–7. [11] Roh M, Han M, Kim D, Chung K. Sebum output as a factor contributing to the size of facial pores. Br J Dermatol vol 2006;155:890–4. [12] Marples R. Sex, constancy, and skin bacteria. Arch Dermatol Res 1982;272:317–20. [13] Green JM, Bishop PA, Muir IH, Lomax RG. Gender difference in sweat lactate. Eur J Appl Physiol 2000;82:230–5. [14] Yosipovitch G, Reis J, Tur E, Sprecher E, Yarnitsky D, Boner G. Sweat secretion, stratum corneum hydration, small nerve function and pruritus in patients with advanced chronic renal failure. Br J Dermatol 1995;133:561–4. [15] Foster KG, Ellis FP, Dore´ C, Exton-Smith AN, Weiner JS. Sweat responses in the aged. Age Ageing 1976;5:91–101. [16] Ohman H, Vahlquist A. In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis. Acta Derm-Venereol 1994;74:375–9. [17] Ehlers C, Ivens UI, Møller ML, Senderowitz T, Serup J. Females have lower skin surface pH than men. Skin Res Technol 2001;7:90–4. [18] Seidenari L, Smith U, Krotkiewski M, Bjorntorp P. Cellularity in different regions of adipose tissue in young men and women. Metabolism 1972;21: 1143–53. [19] Shuster S, Black M, McVitie E. The influence of age and sex on skin thickness, skin collagen and density. Br J Dermatol 1975;93:639–43. [20] Sandby-Moller J, Poulsen T, Wulf H. Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits. Acta Derm-Venerol 2003;83:41–3. [21] Panyakhamlerd K, Chotnopparattara P, Taechakraichana N, Kukulprasong A, Chaikittisilpa S, Limpaphayom K. Skin thickness in different menopausal status. J Med Assoc Thai 1999;82:352–6. [22] Leveque JL, Corcuff P, de Rigal J, Agache P. In vivo studies of the evolution of physical properties of the human skin with age. Int J Dermatol 1984;23: 322–9. [23] Brincat M, Kabalan S, Studd JWW, Moniz CF, De Trafford J, Montgomery J. A study of the decrease of skin collagen content, skin thickness and bone mass in the post menopausal woman. Obstetr Gynecol 1987;70:840–5. [24] Alexander H, Cook T. Variations with age in the mechanical properties of human skin in vivo. J Tissue Viability 2006;16:6–11. [25] Brincat M, Moniz CF, Studd JW, Darby AJ, Magos A, Cooper D. Sex hormones and skin collagen content in post-menopausal women. Br Med J 1983;287: 1337–8.
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