Changes in the Vulva and Vagina Throughout Life

Miranda A. Farage

Feminine Care Clinical Sciences, The Procter & Gamble Company, Cincinnati, Ohio, U.S.A.

Howard I. Maibach

Department of Dermatology, University of California School of Medicine, San Francisco, California, U.S.A.

Aikaterini Deliveliotou and George Creatsas

Second Department of Obstetrics & Gynecology, University of Athens Medical School, Aretaieion Hospital, Athens, Greece

INTRODUCTION

The vulva and vagina change over the course of life. The most salient changes are hormonally mediated and are linked to the onset of puberty, the menstrual cycle, pregnancy, and menopause. This chapter reviews the morphology and physiology of the vulva and the vagina from infancy to old age (Table 1).

With kind permission of Springer Science and Business Media, portions of this review are reproduced from Farage M, Maibach H. Lifetime changes in the vulva and vagina. Arch Gynecol Obstet 2006; 273(4):195-202, online at http://dx.doi.org/10.1007/s00404-005-0079-x.

Table 1 The Vulva and Vagina from Infancy to Old Age

Life stage2* Pertinent physiology

Newborn Effects of residual, transplacental maternal estrogens

Early childhood Lack of stimulation by adrenal or gonadal steroid hormones

Puberty Adrenal and gonadal maturation ensue. Secondary sex characteristics are acquired and menstruation begins (1)

Reproductive years

The menstrual cycle

Vulvar characteristics

Vaginal features

Plump labia majora Well-developed labia minora Immature hair follicles and sebaceous glands

Mons pubis and labia majora lose fat

Benign labial adhesions, if present, normalize without treatment (8)

Subcutaneous fat is deposited in the mons pubis and labia majora

The vulvar epithelium thickens The labia minora and clitoris become more prominent Pubic hair emerges

The morphology of the vulva is mature

Vulvar skin thickness remains constant throughout the menstrual cycle (33)

Stratified squamous epithelium high in glycogen content Lactic acid-producing microbes colonize the vagina shortly after birth White or blood-tinged vaginal discharge may be present (3) The vaginal epithelium thins, is less stratified, and has a low glycogen content

Vaginal pH is neutral or alkaline

Cell densities of lactic acid-producing microbes decrease

The vaginal epithelium thickens and stratifies

Cyclical changes in intracellular glycogen content ensue Cervico-vaginal secretions are produced

Cell densities of lactic acid-producing microbes rise (5) Vaginal epithelial thickness, parakeratosis, and glycogen content rise at midcycle (32,33) Lactic acid-producing microbes are numerically dominant in healthy women (35,36)

Pregnancy

Postmenopause

Blood volume increases. The menstrual cycle ceases during gestation

Follicular function and the menstrual cycle cease. The prevalence of urinary and fecal incontinence rises. Physical health, immune function, tissue regeneration capacity, and cognition may be compromised with increasing age

Parakeratosis of the vulvar stratum corneum rises at midcycle (32,33)

Hair may darken along the midline of the abdomen Increased blood flow heightens vulvar coloration Susceptibility to vulvar varicose veins increases (37) Connective tissue relaxes Flattening of the fourchette and perineal trauma may occur during delivery Pubic hair becomes sparse Subcutaneous fat is lost Vulvar tissue atrophies The risk of perineal dermatitis rises in older women with incontinence

Menstrual cyclicity becomes established (12,13) Cervico-vaginal secretions become thicker, clearer and more elastic prior to ovulation

Connective tissue relaxes and vaginal muscle fibers thicken The risk of Candida infection increases (38)

Following delivery, the morphology and dimensions of the vaginal tract are re-established

The vaginal epithelium atrophies Cervico-vaginal secretions become sparse

Vaginal pH rises; colonization by enteric microflora may rise Atrophic vaginitis is common

"Because of inter-individual variations, the age definition of each life stage is approximate. The newborn period lies between birth and one month of age; early childhood refers to between one and eight years of age. Puberty usually occurs between eight and 15 years, although the age criteria for premature puberty are controversial. The reproductive years begin at menarche (mean age of about 12 years) and continue through the perimenopause. Menopause is defined to begin one year following the final menstrual period; menstruation ceases at a median age of 50 in Western industrialized countries. Source: Adapted from Ref. 57.

INFANCY AND EARLY CHILDHOOD

The vulva and vagina of the newborn exhibit the effects of residual maternal estrogens (Fig. 1). At birth, the labia majora appear plump. The labia minora are well developed and may protrude beyond the labia majora. Similarly, the clitoris may appear disproportionately large. The vaginal introitus is visible but small (typically 4 to 5 mm in girls under the age of five). The hymen may appear thick and fibriated, a hymenal configuration common in girls under the age of three years. Bartholin's glands are visible and Skene's (paraurethral) glands are well formed. The urethral opening is not easily discerned. The vaginal epithelium is glycogen-rich and is colonized with lactic acid-producing microbes, such as Lactobacillus species, within the first 24 hours of birth (1). A physiologic, white mucoid vaginal discharge may be present. As residual levels of maternal estrogen diminish, this discharge may become tinged with blood from withdrawal endometrial bleeding (2,3).

These estrogenic effects dissipate between the fourth and eighth postnatal weeks. The labia majora lose fat and the prominence of the clitoris and labia minora diminishes (Fig. 2). The vaginal epithelium loses its stratification and gly-cogen content and becomes much thinner. The vaginal pH becomes neutral or

Vulva Puberty
Figure 1 Anatomy of the newborn vulva. (See color insert p. 2. )
Labia Minora Puberty Changes
Figure 2 Anatomy of the prepubescent vulva. (See color insert p. 3.)

alkaline, presumably because of a relative deficiency of acid-producing vaginal microbes (4,5). Vulvar skin thickness decreases and the mons pubis and labia majora lose some of the subcutaneous fat present at birth (6,7). Although the full complement of vulvar hair follicles and sebaceous glands is thought to be present from birth, these structures do not mature until the adrenal glands are activated at puberty. The prepubescent labia minora have barely discernible vellus hair follicles that are lost at puberty when the follicles of the labia majora and mons pubis terminally differentiate (6). The appearance of the prepubescent hymen is variable. Two common forms in girls more than three years of age are:

1. The annular hymen that surrounds the introitus in a regular fashion, and

2. The crescentic hymen, a crescent-shaped conformation present along the posterior vaginal orifice only, the ends of which are attached to the lateral vaginal wall.

Labial adhesions occur more commonly in younger prepubertal girls (aged three months to six years, with a peak incidence at 13 to 23 months of age), creating a flat vulvar appearance (8). This acquired condition is the result of low estrogen levels in the prepubertal child and possibly of a chronic inflammatory process. First-line treatment with estrogen cream is recommended.

A failure to respond to medical therapy requires consideration of other options, which include in-office treatment with manual separation after topical anesthesia or, rarely, separation under sedation in an outpatient setting or surgical suite (9).

PUBERTY

Pubertal changes in the vulva and vagina are induced by adrenal and gonadal maturation. Puberty generally begins between ages 8 and 13 years. Physical changes associated with puberty are an accelerated growth rate, the appearance of pubic hair (pubarche), the appearance of axillary hair, breast development (telarche), and the onset of menstruation (menarche). The timing and stages of development of secondary sex characteristics were first defined in Marshall and Tanner's seminal study of 192 girls in a British orphanage (10).

Maturation of the adrenal glands and androgen secretion (adrenarche) begin at about age six, approximately two years before pituitary-gonadal maturation and the production of ovarian steroid hormones (gonadarche). Because adrenarche and gonadarche proceed independently, the appearance of pubic hair does not provide information about pituitary-ovarian maturation. Pubic hair development elicited by androgens proceeds in five stages as described by Tanner (Fig. 3) (10):

1. No pubic hair.

2. Sparse hair appears on the labia majora and the mons pubis along the midline.

3. Thickness and coarseness of the hair increase, with coverage of the lobes of the labia majora and increased lateral growth from the midline of the mons pubis.

4. Hair growth increases such that only the upper lateral corners of the mature triangular configuration are deficient.

5. Adult pattern, attained between the ages of 12 and 17 years, with a characteristic horizontal upper margin on the mons pubis just above the limit of the genitofemoral folds.

In most ethnic groups (except for women of Asian or Native American heritage), hair coverage extends from the labia to the upper aspects of the thighs.

Gonadal maturation usually occurs during the two years preceding menarche. During the maturation process, follicular development causes estrogen production

Figure 3 Tanner stages of pubic hair development. Source: Adapted from Ref. 57.

Figure 3 Tanner stages of pubic hair development. Source: Adapted from Ref. 57.

to rise. The vaginal epithelium thickens and intracellular glycogen production begins. The cervix and vagina increase in size, the vaginal fornices develop, cervi-covaginal secretions are produced, and vaginal fluid becomes acidic.

Vulvar morphology matures at this time. Fat deposition occurs in the mons pubis and labia majora. The vulvar epithelium increases in thickness (7), labial skin becomes rugose, the clitoris becomes more prominent, the vestibular glands become active, the introitus increases in diameter, and the urethral orifice is more discernible. Vaginal discharge may be evident between the anterior folds.

Breast development, influenced by estrogens, is also described by five Tanner stages, from no development (Stage 1) to the mature adult breast (Stage 5) (10). Menarche occurs near the end of the Tanner sequence of breast changes, typically sometime between the ages of 11 and 15 years (1). The mean age of menarche worldwide is between 12 and 13 years (11). The sequence from the first appearance of pubic hair through breast development and menarche takes about four years. Normative menstrual cycle length is established by the sixth gynecologic year (i.e., the sixth year following menarche), usually around the chronologic age of 19, although this may occur anytime between the ages of 17 and 21, depending on menarcheal age (12,13).

Idiopathic Precocious Puberty

Historically, puberty had been defined as precocious in girls when secondary sex characteristics (particularly breast development) appeared prior to the age of eight. However, an apparent advance in the age of onset of pubertal changes has been observed in the United States and in girls from developing countries who have migrated to Western Europe for foreign adoption (reviewed in Ref. 14). Two large studies in the U.S. found that pubertal signs may appear before the age of eight, especially in African American as compared to Caucasian girls (Tables 2 and 3) (15-17). Between the 1970s and 1990s, the average age of menarche in the U.S. fell from 12.75 years to 12.54 years (17).

Table 2 Mean Onset of Secondary Sex Characteristics (Tanner Stage 2) and Menarche in Caucasian and African-American Girls from North American Suburban Medical

Practices (1997)

Table 2 Mean Onset of Secondary Sex Characteristics (Tanner Stage 2) and Menarche in Caucasian and African-American Girls from North American Suburban Medical

Practices (1997)

Ethnicity

Mean age of onset (years)

% with Pubertal signs by age 8

Menarche

Breast development

Pubic hair

African

12.16

8.87

8.78

48.3

American

(SD 1.21)

(SD 1.93)

(SD 2.00)

Caucasian

12.88

9.96

10.52

14.7

(SD 1.20)

(SD 1.82)

(SD 1.67)

Abbreviation: SD, standard deviation. Source: Adapted from Refs. 10, 15, 57.

Abbreviation: SD, standard deviation. Source: Adapted from Refs. 10, 15, 57.

Table 3 Mean Age of Menarche and Median Age of Onset of Secondary Sex Characteristics (Tanner Stage 2) (10) by Race from the U.S. Third National Health and Nutrition Examination Survey (NHANES III) (1988-1994)

Ethnicity

Age (years)

Menarchea

Breast development1"

Pubic hairb

African

12.14

9.48

9.43

American

(SE: 11.87-12.39)

(FL: 9.14-9.76)

(FL: 9.05-9.74)

Caucasian

12.60

10.38

10.57

(SE: 12.48-12.71)

(FL: 10.11-10.65)

(FL: 10.29-10.85)

aMean age of menarche. From Ref. 17.

Median age at which 50% of the sample entered Stage 2 of pubertal development. FL based on probit analysis for multiple race comparisons at the 95% confidence level (16). Abbreviation: FL, fiducial limit. Source: Adapted from Ref. 57.

aMean age of menarche. From Ref. 17.

Median age at which 50% of the sample entered Stage 2 of pubertal development. FL based on probit analysis for multiple race comparisons at the 95% confidence level (16). Abbreviation: FL, fiducial limit. Source: Adapted from Ref. 57.

Controversy surrounds the clinical significance of these findings. Most cases of early pubertal development are idiopathic and probably do not represent precocious puberty unless bone maturation and developmental characteristics are so accelerated that diminished adult height is likely (18,19). However, because true endocrine pathology may be overlooked if early pubertal signs are dismissed, vigilant longitudinal follow-up of girls with early pubertal onset is advised (20). Several risk factors (genetics, low birth weight, higher body mass index, exposure to endocrine disruptors) are correlated statistically with earlier pubertal onset, but the biological mechanisms of accelerated onset are unknown (17,21-31).

REPRODUCTIVE YEARS

Changes in the vulva and vagina during the reproductive years are linked to the menstrual cycle and pregnancy.

Vulvar and Vaginal Effects of the Menstrual Cycle

Vulvar epithelial thickness is at its highest in the reproductive years (Fig. 4). Vulvar skin thickness remains constant over the menstrual cycle, but its surface cells are predominantly orthokeratotic (lacking nuclei) at the beginning and end of the cycle, and increasingly parakeratotic (bearing a degenerated nucleus) at midcycle (32). These cytological changes are thought to be mediated by estrogen: parakeratosis of vulvar epithelial cells is rare in postmenopausal women but rises dramatically in response to systemic estrogen supplementation (32). The vaginal epithelium is sensitive to ovarian steroid hormone cycling. Estrogen stimulation causes the thickness, glycogen content, and parakeratosis of the vaginal epithelium to peak approximately at midcycle (Fig. 5) (33).

0.25

□ Rete peg length beyond the

epidermis ■ Sub-stratum corn eu m epidermal layers □ Stratum corneum

1-14

15-50

Age range (years)

51-56

61-86

Figure 4 Epithelial thickness of the labia majora with age. Source: Based on data in Ref. 7.

1-14

15-50

Age range (years)

51-56

61-86

Figure 4 Epithelial thickness of the labia majora with age. Source: Based on data in Ref. 7.

During menstruation, vaginal pH rises as high as six on day 2 and drops to approximately five by day 4 (34). The impact of the menstrual cycle on the microbial ecology of the vagina is not well understood. Studies using traditional culture techniques suggest that Lactobacillus species predominate in the vaginal flora of healthy women and that their cell densities remain relatively constant over the menstrual cycle (35). However, such techniques typically identify only the most readily cultivated microbial populations, which may represent but a subset of the extant community. Emerging data obtained by analysis of total microbial community DNA indicate that lactic acid-producing species such as Atopobium, Megasphaera, and Leptotrichia, rather than Lactobacillus, are numerically dominant in some women (36). Consequently, genera besides Lactobacillus may contribute to the acidity of vaginal tract, but the impact of the menstrual cycle on these genera has not been studied.

Vulvar and Vaginal Effects of Pregnancy and Delivery

During pregnancy, an increase in total blood volume heightens the coloration of the vulva and the vagina. The connective tissue of the vulva, vagina, and perineum relaxes and the muscle fibers of the vaginal wall increase in size in preparation for delivery. Progesterone elevates venous distensibility, which may cause varicose veins in the vulva (37). Pregnancy is associated with a 10- to 20-fold increased incidence of vulvovaginal candidiasis (38).

During delivery, the perineal and the vaginal musculature relax; the vaginal rugae flatten to allow expansion of the vaginal tract, accommodating passage for

Vagina Variation
Figure 5 Menstrual cycle variations in (A) vulvar skin and (B) vaginal mucosa. Source: Adapted from Ref. 33.

the infant. Injury to the perineum can occur spontaneously or because of episiot-omy. After delivery, the vaginal introitus is wider and the fourchette appears more flattened. Over the next 6 to 12 weeks, the morphology and dimensions of the vaginal tract are reestablished (39).

MENOPAUSE AND OLDER AGE

Menopause is the permanent cessation of menstruation due to the loss of follicular activity. A constellation of symptoms emerges during the perimenopause, the transition period to menopause. The most notable is menstrual cycle irregularity, reflecting an increase in the number of anovulatory cycles and cycles with a prolonged follicular phase. Some women experience cramps, bloating, or breast tenderness; symptoms of estrogen depletion, such as vasomotor symptoms (hot flashes), migraine, and vaginal dryness, can ensue. The perimenopause commences typically after the age of 45 and lasts about four years. Menstruation ceases at a median age of 50 in Western industrialized societies (40). Menopause is considered established one year after the final menstrual period (41).

Following menopause, pubic hair grays and becomes sparse, the labia majora lose subcutaneous fat, and the labia minora, vestibule, and vaginal epithelium atrophy (7,42). At the cytological level, estrogen-induced parakeratosis of vulvar stratum corneum is highest in the third decade of life, but rarely seen by the eighth decade (43).

Postmenopausal atrophic vulvovaginitis is a common condition. Vaginal secretions decrease, reducing lubrication and increasing coital discomfort. Thinned tissue is irritated more easily and may be more susceptible to infection. The vaginal pH rises and the prevalence of colonization by enteric organisms associated with urinary tract infections increases (44). In addition to these physiologically induced changes, certain vulvar dermatoses, such as lichen sclerosus, are most prevalent in peri- and postmenopausal women (45).

Vulvar skin differs from exposed skin in the characteristics of skin hydration, friction, permeability, and visually discernible irritation (reviewed in Ref. 46). It is assumed commonly that aged skin is intrinsically less hydrated, less elastic, more permeable, and more susceptible to irritation. As discussed later in this chapter, however, assessments of the vulvar skin of pre- and post-menopausal women by means of bioengineering techniques did not reveal large age-related changes in these characteristics (Table 4).

For example, the skin of the labia majora is more hydrated than forearm skin as measured by transepidermal water loss and its coefficient of friction is higher (47,48). Although small age-related changes in these parameters were measured on the forearm of pre- and postmenopausal women, the impact of the menopause on the water barrier function and friction coefficient of vulvar skin was negligible (Table 4) (48).

Vulvar skin is more permeable to hydrocortisone than forearm skin, but comparable testosterone penetration rates have been measured at both sites. In postmenopausal women, skin permeability to hydrocortisone drops on the forearm but not on the vulva, and no age-related differences in testosterone penetration were found at either site (Table 4) (49). (For perspective, penetration of testosterone but not hydrocortisone may be mediated by androgen receptors.)

Exposed forearm skin was more susceptible than vulvar skin to the model irritant, aqueous sodium lauryl sulfate (1% w/v). This agent caused intense erythema on the forearms of premenopausal women, but no visually discernable response on the vulva in either pre- or postmenopausal women (Table 4) (50).

Table 4 Physiologic Skin Parameters in Pre- and Postmenopausal Women

Parameter

Site

Age groupa Measured value Significance Reference

Water barrier function (TEWL, g/m2.hr)

Forearm Premenopausal 3.7 + 0.4

Postmenopausal 2.6 + 0.3

Vulva Premenopausal 14.8 + 1.5

Postmenopausal 13.5 + 1.8

Skin hydration (capacitance, AU)

Forearm Premenopausal 93.3 + 2.3

Postmenopausal 91.9 + 2.8

Premenopausal 116.8 + 4.1

Postmenopausal 118.0 + 8.2

Vulva

Friction coefficient, m Forearm

Vulva

Premenopausal Postmenopausal Premenopausal Postmenopausal

Hydrocortisone penetration (% dose absorbed)

Forearm Premenopausal 2.8 + 2.4 Postmenopausal 1.5 + 1.1 Vulva Premenopausal 8.1 + 4.1 Postmenopausal 4.4 + 2.8 Testosterone penetration (% dose absorbed)

Forearm Premenopausal 20.2 + 8.1 Postmenopausal 14.7 + 4.2 Vulva Premenopausal 26.7 + 8.0 Postmenopausal 24.6 + 5.5 Number of positive visual erythema scores (on day 2, after 24-hr exposure to Forearm Premenopausal 9 P = 0.03

Postmenopausal 5 Vulva Premenopausal 0 NS

Postmenopausal 0

aGroup sizes (water barrier function, skin hydration and friction parameters): premenopausal—34 subjects, postmenopausal—10 subjects. Group sizes (hydrocortisone and testosterone penetration): 9 subjects in each group. Visual erythema score to sodium lauryl sulfate (SLS) application: 10 subjects per age group.

Level of statistical significance of age-group difference. Abbreviation: n.s., not significant. Source: Adapted from Ref. 57.

Although large age-related differences in skin vulvar permeability and intrinsic susceptibility to irritants have not been demonstrated, dermatitis of the vulva, perineum, and buttocks can be a substantial problem in older people with incontinence. A mechanistic understanding of the etiology of incontinence dermatitis was first developed from studies on diapered infants and then extended to older adults. Chapter 12 provides a detailed explanation of the mechanistic factors that contribute to incontinence dermatitis. The etiology is multifactorial. In brief, exposure to urinary moisture under occlusion makes the skin more susceptible to friction damage; urinary ammonia elevates the local pH, which alters skin barrier function and activates fecal enzymes; these enzymes further compromise skin integrity and increase skin susceptibility to microbial infection (51-55). Incontinence dermatitis is particularly debilitating in older adults because urine and feces exert their effects against a background of atrophied tissue, immobility, a potentially weakened immune response, and often compromised physical health and cognition. Several factors exacerbate the deleterious effects of skin wetness, occlusion, and fecal enzyme action in elders. Although the baseline skin wetness level does not differ significantly in aged skin, the excess hydration induced by occlusion is significantly greater and dissipated more slowly in older skin than in young skin (56). Although the coefficient of friction of vulvar skin is unchanged in older women, reduced mobility subjects atrophied genital tissue to higher shear forces than those encountered by infants. Moreover, atrophied genital tissue may be more susceptible to pH changes and enzymatic action, while immune function and tissue regeneration capacity also may be compromised. Lastly, elders may not receive the same degree of attentiveness as infants and those with impaired cognition may be unable to alert caregivers to incontinent episodes. These factors underscore the need for vigilant care and proper hygiene to help maintain healthy urogenital skin in older women with incontinence.

CONCLUSION

In summary, the vulva and vagina undergo characteristic age-related changes in morphology and physiology over the course of a lifetime. At birth, these tissues exhibit the effects of residual maternal estrogens. During puberty, the vulva and vagina mature under the influence of adrenal and gonadal steroid hormones. During the reproductive years, the vagina responds to ovarian steroid hormone cycling and both tissues adapt to the needs of pregnancy and delivery. Following menopause, the vulva and vagina atrophy. A rise in the prevalence of incontinence among older women increases the risk of vulvar and perineal dermatitis. Vigilant care is needed to avoid dermatitis in the older person with incontinence, as the condition is particularly debilitating at this stage of life.

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56. Roskos KV, Guy RH. Assessment of skin barrier function using transepidermal water loss: effect of age. Pharm Res 1989; 6:949.

57. Farage MA, Maibach HI. Lifetime changes in the vulva and vagina. Arch Gynecol Obstet 2006; 273(4):195-202, online at http://dx.doi.org/10.1007/s00404-005-0079-x.

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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Responses

  • Eric
    Why during maturation vagina changes?
    3 years ago
  • anja
    How is vulvas adapted to its function?
    3 years ago
  • amalda
    Does inner labia minora change while one is about to menstruate?
    2 years ago
  • Phillipp Duerr
    How is the vagina and vulva adapted to delivery?
    2 years ago
  • aatos
    Why subcutaneous fat in labia majora is less in puberty?
    2 years ago
  • manfredo
    How the vagina changes from child hood to old age?
    2 years ago
  • Thomas
    What changes in vagina during premenstruation?
    2 years ago
  • S SJ
    Which are the changes in genetials during periods?
    2 years ago
  • antonio
    How does the inside of your vaginachange when on period?
    1 year ago
  • frida
    Is there vegina colour vary from infancy to adulthood?
    1 year ago
  • DEMSAS YEMANE
    Does the vagina change in size during menstruation?
    1 year ago
  • marigold
    Does genital change during period?
    10 months ago
  • Nunzia
    What does vagina supposed to look like before puberty?
    3 months ago

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