European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819 www.elsevier.

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Review

Do panty liners promote vulvovaginal candidiasis or urinary tract infections? A review of the scientic evidence
Miranda Farage a,*, Mario Bramante b, Yoshiko Otaka c, Jack Sobel d
a The Procter & Gamble Company, Cincinnati, OH, USA Procter & Gamble Service GmbH, Schwalbach am Taunus, Germany c Department of Gynecology and Obstetrics, Kanto Medical Center NTT EC, Tokyo, Japan d Wayne State University School of Medicine, Department of Infectious Diseases, Detroit, MI, USA b

Received 7 April 2006; received in revised form 5 October 2006; accepted 27 November 2006

Abstract Panty liners are used to absorb light menstrual ow, vaginal discharge, or urine leakage, or to maintain a clean, dry feeling. Allegations that panty liners may trap heat and moisture to promote vulvovaginal candidiasis (VVC) or promote colonization by microbes that contribute to urinary tract infections appear to be unfounded. As reviewed herein, measurements of the impact of panty liners on skin temperature and skin surface moisture had no clinically meaningful effect on cell densities of genital microora. Epidemiological investigations of a potential link to VVC were either negative or were inconclusive because of confounding factors. Although enteric microbes reside on the vulva and perineum, no evidence exists that panty liner use promotes urethral colonization by enteric microbes. Moreover, a series of 13 randomized prospective trials of panty liners or ultra-thin pads demonstrated no clinically signicant adverse effects either on the skin or on isolation frequencies or cell densities of representative genital microora. Post-market surveillance systems suggest a low incidence of complaints. Evidence from vulvar clinic patients reveals no signicant contribution of these products to persistent vulvar symptoms. Taken together, the scientic evidence supports the conclusion that panty liners are safe when used as intended and do not promote VVC or urinary tract infections. # 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Panty liner; Genital infections; Vulvovaginal infections; Vulvovaginal candidiasis; Urinary tract infections

Contents 1. 2. 3. Product designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Usage practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Questions about the health effects of panty liners . . . . . . . . . . . . . 3.1. Skin temperature, skin hydration, and microbial colonization. 3.2. Vulvovaginal candidiasis (VVC) risk . . . . . . . . . . . . . . . . . 3.3. Risk of urinary tract infections (UTIs) . . . . . . . . . . . . . . . . Toxicological and clinical evidence for panty liner safety . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 9 9 9 10 16 16 18 18 18

4. 5.

* Corresponding author at: The Procter & Gamble Company, Winton Hill Technical Center, 6110 Center Hill Road, Box 136, Cincinnati, OH 45224, USA. Tel.: +1 513 634 5594; fax: +1 513 634 7364. E-mail address: farage.m@pg.com (M. Farage). 0301-2115/$ see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2006.11.015

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

Panty liners are small, thin pads most commonly used to absorb vaginal discharge between the menstrual periods. Introduced in the 1970s in North America and Europe, panty liners are now available worldwide. Some women use panty liners daily, but questions about the healthfulness of this practice occasionally arise. This reviews the reasons that women use panty liners, examines panty liner use as a risk factor for vulvovaginal candidiasis (VVC) and urinary tract infections (UTIs), and presents clinical evidence supporting the safety of panty liners.
Fig. 1. Reasons for panty liner use.

1. Product designs Panty liners are small, thin pads consisting of a permeable surface layer (topsheet), an absorbent core, and a uidimpervious back layer (backsheet) that protects the undergarment and attaches to it by an adhesive strip. The topsheet captures and draws uid into the absorbent core. Topsheets are made from non-woven polyethylenebased or polypropylene-based copolymeric fabrics, perforated polyethylene lms, or combinations thereof. Although non-woven fabrics look more like cotton, their chemical composition is similar to that of perforated lms. However, perforated lms provide the additional benet of keeping the pad surface clean and dry. Todays improved perforated lms have a supple, cloth-like quality that feels more like fabric against the skin. Because panty liners are designed to absorb small amounts of uid, the core is usually composed of a thin layer of cellulose uff pulp. Alternative cores consist of superabsorbent bers or granules wrapped in cellulose tissue. The latter are extremely thin (13 mm) yet absorb as much uid as conventional uff pulp cores (>10 mm thickness). Many women nd the thinner liners to be particularly discreet and comfortable. A few brands include perfumes to mask odor, but most brands are perfume-free. Some brands incorporate novel odor-control technologies, such as polyacrylate granules or zeolites wrapped in a tissue core. Zeolites are small, inert mineral particles with pores of variable sizes that trap volatiles: they absorb rather than mask discharge odor. Breathable panty liners with vapor-permeable or air/ vapor-permeable backsheets are another recent innovation. These products should improve the perception of skin dryness by reducing the degree of occlusion. Fashionconscious designs include a variety of shapes and colors that complement current undergarment styles. reasons are [1] to absorb menses (e.g., in anticipation of the onset of menstruation, at the end of the menstrual period, and as a backup when using tampons); [2] to absorb vaginal discharge (e.g., excessive discharge, post-coital discharge, or daily discharge), and [3] to absorb urine (e.g., for light stress or urge incontinence). Panty liners are suited to these needs because they are absorptive yet comfortable, discreet, portable, and disposable. In North America and Western Europe, 1030% of women wear panty liners daily between the menstrual periods. Their ideal is staying clean and dry at all times.

3. Questions about the health effects of panty liners Questions about the potential health effects of panty liners arise occasionally. The most commonly expressed concern is that panty liners may trap heat and moisture against the skin, thereby increasing the risk of VVC. It is also alleged that panty liner use may increase the risk of UTIs by facilitating the transfer of intestinal microbes from the perianal region. The weight of the evidence fails to support a link between panty liner use and clinically excessive skin moisture, VVC risk, or the risk of infection with enteric microbes. Evidence from the peer-reviewed scientic literature is reviewed in brief below. 3.1. Skin temperature, skin hydration, and microbial colonization Vulvar skin occlusion is a condition of everyday life, a consequence of the anatomy of the external female genitalia coupled with undergarment and outer garment wear. Vulvar skin has a higher level of surface moisture than exposed forearm skin, as assessed by trans-epidermal water loss (TEWL) [1,2]. Vulvar skin also may be more intrinsically hydrated than exposed skin, because TEWL from vulvar skin remains elevated relative to forearm skin even after equilibration with the environment or after prolonged drying of both sites with a dessicant [2,3].

2. Usage practices As the product name implies, panty liners serve as thin, undergarment liners that absorb discharge. About 50% of women in North America and Western Europe use panty liners. Fig. 1 shows common reasons for use. The primary

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M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

Occlusive articles affect skin temperature, skin surface moisture, and the relative humidity in the microenvironment between the skin and the article. Panty liners have a measurable impact on skin temperature and skin surface moisture, but the magnitude of these effects does not create a meaningful change in the risk of genital infections. A series of studies demonstrated the impact of panty liners on these variables [46]. An increase of approximately 1 8C in the mean temperature of the labium majus was measured in women who wore panty liners with impervious, non-breathable backsheets compared to women who wore no panty liners. For perspective, a change of this magnitude is comparable to intra-day uctuations that have been observed at various anatomical sites due to changes in ambient temperature, food intake, exercise, or circadian rhythms [711]. A 34% increase in the rate of evaporation of skin surface moisture was measured immediately after underwear/liner removal in users of panty liners with impervious backsheets compared to non-users, although hydration of the underlying epidermis was unchanged [4]. However, panty liners with impervious backsheets caused no visual skin reactions [12]; moreover, although the cell density of total aerobic microbes on the labium majus was statistically higher in users of panty liners with impervious backsheets compared to non-users, the difference was about 0.3 log units, a clinically insignicant change. No difference was observed in labial cell densities of the potential pathogens, Candida albicans, Escherichia coli, Enterococci, Group B streptococci, and S. aureus. These observations are consistent with the results of a 6month prospective clinical trial of panty liners (Table 1), which demonstrated no difference between daily panty liner users and non-users in the cell densities of C. albicans and other yeasts, G. vaginalis, S. aureus, coliforms, and enterococci [13]. Hence, the scientic evidence does not support a link between panty liner use and the risk of infection with these common vulvovaginal microbes. New material technologies have enabled the development of next-generation breathable panty liners with vaporpermeable or air/vapor-permeable backsheets. When applied to the forearm, feminine hygiene articles with vapor-permeable backsheets lowered skin surface water loss, skin hydration, and the relative humidity of the microenvironment between the pad and the skin under moderate conditions of environmental temperature and relative humidity (25 8C/50% relative humidity) [6]. Wearing panty liners with vapor-permeable backsheets and superabsorbent cores maintained vulvar skin temperature, skin wetness, and skin pH at levels more comparable to those observed with no panty liners; differences in vulvar microora between the groups were negligible [4,12]. These studies suggest that breathable panty liners may improve the wearers comfort by facilitating the transfer of heat and surface moisture from the skin.

3.2. Vulvovaginal candidiasis (VVC) risk Historically, epidemiological studies were the only data available to address the premise that occlusive garments and articles may trap heat and moisture in the genital region, allegedly creating an environment for yeast to multiply. Such retrospective studies are a relatively blunt tool compared to the bioenginerering methods and investigative trials described above, but they are included here to afford comprehensive review of all the data. Most epidemiologic data on the putative association of VVC with tight clothing, synthetic underwear, and pad and panty liner use are inconclusive or negative. Two North American casecontrol studies involving Mid-western university students (157 and 1300 participants) found no association of VVC with tight-tting clothing, synthetic fabric underwear, panty hose, type of menstrual protection, or pad use between periods [14,15]. Potential links to recurrent rather than episodic VVC have been examined also. A Nigerian study found higher cell densities of vulvovaginal C. albicans in patients with recurrent VVC who lived in poor sanitary conditions and who wore tight tting clothing or synthetic underwear most of the time compared to patients who wore loose dresses [16]. Because all patients were symptomatic, the clinical signicance of the observed differences is unclear. By contrast, a prospective study of 163 Spanish sex workers found no connection between recurrent VVC and wearing tight clothing or synthetic underwear [17]. A survey of perianal colonization with Candida species, a potential reservoir for urogenital re-colonization, found no association with wearing tight-tting trousers or synthetic fabric underwear [18]. More recently, a retrospective study of women on maintenance antifungal therapy linked patient-reported and non-laboratory-conrmed cases of recurrent VVC with wearing panty liners in the same week or in the week before an episode [19]. Confounding factors may contribute to a statistical but non-causal relationship. First, patient-reported diagnoses are unreliable because diagnoses based solely on signs and symptoms can be inaccurate 5070% of the time [20,21]. Secondly, panty liner use may result from, rather than cause, vaginal symptoms because the products are used to absorb excessive discharge such as that associated with infection. Panty liners also are used in anticipation of menses, a time when VVC patients often report an exacerbation of symptoms. Finally, panty liners may be used to absorb post-coital discharge; although the study in question found no association between sexual practices and symptomatic VVC episodes, monthly intercourse frequency, intercourse frequency in the weeks preceding infection, and oral intercourse frequency in the month prior to infection are behavioral risk factors for both episodic and recurrent VVC [15,22,23]. Consequently, the association of panty liners with recurrent VVC episodes in this selected population may not be causal.

Table 1 Clinical trials on panty liners or ultra-thin menstrual pads (19812005)a Study number Product comparison Region Study groups Group sizes 62 Evaluation periodb and use characteristics 6 cycles (daily inter-menstrual panty liner use; own products ad lib for menstrual protection) Clinical endpoints and results

Studies on panty liners or product combinations 1 New panty liners (perfumed North America (Midwest, and non-perfumed) vs. no summer through early fall) panty liner

Perfumed panty liner (perforated lm topsheet)

Vaginal and vulvar microbiology: no signicant difference in microbial isolation frequencies or semi-quantitative cell densities between groups [13]

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

Non-perfumed panty liner (perforated lm topsheet) No panty liner 2 New menstrual pads, minipads and panty liners designed for adolescents vs. analogous, standard products North America (Midwest, fall through early winter) Non-perfumed test product designed for adolescents (perforated lm topsheet) Standard, commercially available, competitive products (non-woven topsheet)

61 67 55 3 cycles (ad lib use by adolescents for menstrual and inter-menstrual protection) Gynecological exam: no adverse effects

50

Dermatological assessment: all subjects had normal skin condition at study inception and completion Vaginal and vulvar microbiology: no differences in isolation frequencies of representative endogenous ora Procter & Gamble unpublished data, April 1984 1 cycle (daily, inter-menstrual use) Gynecological exam: one participant in the modied core product group with a history of recurrent vulvovaginal candidiasis had an episode that resolved with treatment. Due to the subjects history, this was not considered a productrelated effect Dermatological assessment: No differences between groups Vaginal and vulvar microbiology: aside from the aforementioned case, no clinically signicant changes in microbial isolation frequencies or semi-quantitative cell densities were observed Procter & Gamble unpublished data, October 1985

Panty liner with modied core vs. conventional panty liner

North America (late spring, through mid-summer)

Non-perfumed panty liner with modied core (perforated lm topsheet)

48

Non-perfumed marketed panty liner (perforated lm topsheet)

46

11

12

Table 1 (Continued ) Study number 4 Product comparison Region Study groups Group sizes 58 Evaluation periodb and use characteristics 3 cycles (daily, inter-menstrual use) Clinical endpoints and results

Panty liner with modied core vs. conventional panty liner

North America (Midwest, early fall, through winter)

Non-perfumed panty liner with modied core (perforated lm topsheet)

Non-perfumed marketed panty liner (perforated lm topsheet)

61

Gynecological exam: two subjects with a history of recurrent vulvovaginal candidiasis (one in each group) had an episode that resolved with treatment. Due to the subjects history, these were not considered product-related effects Dermatological assessment: no effects on skin condition Vaginal and vulvar microbiology: aside from the aforementioned cases, no signicant differences microbial isolation frequencies or semi-quantitative cell densities were observed Procter & Gamble unpublished data, April 1986 Dermatological assessment: slight erythema in a small number of subjects prior to group assignment. No clinically discernable changes in skin condition between groups during product use Diagnostic patch test ( perfume): no evidence of contact sensitization Procter & Gamble unpublished data, March 1988 Dermatological assessment: no product-related adverse effects; negligible signs of irritation Subjective assessments: pad with fabric-like lm preferred for menstrual protection benets. Pads were comparable in terms of comfort [48]

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

Perfumed pad and panty liner vs. non-perfumed pad and panty liner

North America (Midwest, summer through early fall)

Pad and panty liner with new perfume

75

2 cycles (pads for menstrual protection, daily, intermenstrual panty liner wear)

Marketed, perfumed pad and panty liner Marketed, non-perfumed pad and panty liner (all products had perforated topsheets) 6 Menstrual pads with fabriclike surface lm vs. menstrual pad with non-woven fabric surface; discretionary inter-menstrual panty liner use Europe (Greece) (spring through early summer) New menstrual pad with a fabric-like lm surface

78

72

53

2 consecutive cycles of menstrual pad use, with inter-menstrual panty liner use at participants discretion

Marketed menstrual pad with non-marketed panty liner for inter

55

New scented vs. unscented panty liner

North America (Midwest, summer)

Panty liner with new topsheet, tissue core and perfume

35

1 menstrual cycle: baseline evaluation (prior to product wear) followed by 2 weeks of inter-menstrual use, 24 h/day

Non-perfumed marketed panty liner

35

Dermatological assessment: improvement from baseline during the prospective phase. No clinically signicant differences in erythema or skin condition were observed between groups. One participant with a history of perfume allergy had a mild reaction after 2 days and discontinued product use. Results of follow up and repeat use were consistent with pre-existing allergy Subjective assessments: products were rated equally for comfort Procter & Gamble unpublished data Dermatological assessment: no signicant group differences in vulvar erythema or cutaneous moisture Microbiological assessment (semi-quantitative): no signicant group differences in microbial isolation frequencies or semiquantitative cell densities

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

New panty liner with odor control additives vs. two marketed panty liner brands without odor control technology

Europe (Paris, France)

New panty liner with perforated lm topsheet and odor control technologies (zeolites and superabsorbent polyacrylates in combination) Marketed panty liner with perforated lm topsheet and no odor control additives

60

One cycle of daily inter-menstrual panty liner use, 24 h/day, for at least 18 days

60

Three evaluation points: (1) baseline evaluation after cessation of menstrual ow; (2) after 9 days of product use; (3) after the full cycle of inter-menstrual wear, before anticipated onset of menstruation

Competitive commercial product with non-woven topsheet and no odor control additives

60

No product-related adverse effects Procter & Gamble, unpublished data July, 1995

Breathable panty liner with vapor-permeable backsheet and odor control technology vs. conventional non-breathable panty liner and no panty liner

Latin America (Caracas, Venezuela; cool subtropical climate)

Panty liner with hybrid lm/ non-woven topsheet, breathable backsheet, and superabsorbent core with odor-absorbent additives (zeolites)

90 participants: 30

Groups normalized for frequency of cotton or synthetic fabric underwear. Baseline evaluation and 1 cycle of inter-menstrual use, 24 h/day. Three, once-weekly inter-menstrual assessments (days 1314, 2021, and 2528 of cycle)

Dermatological assessment: no signicant group differences in vulvar erythema. When observed, vulvar erythema was slight

13

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Table 1 (Continued ) Study number Product comparison Region Study groups Marketed panty liner with non-woven topsheet, cellulose uff core, and conventional backsheet Group sizes 30 Evaluation periodb and use characteristics Clinical endpoints and results Subjective assessments: no difference in irritation complaints between groups using panty liners or no liners. Panty liners were perceived to confer benets in freshness Procter & Gamble, unpublished data, December 2001 2 cycles (menstrual and daily, inter-menstrual use) Gynecological exam: no adverse effects Dermatological assessment: all subjects exhibited normal skin condition at study completion Vaginal and vulvar microbiology: no signicant difference in isolation frequencies or cell densities at any time point Perineal skin wetness: no signicant difference between groups References [46,47] 2 cycles (menstrual and daily, inter-menstrual use) Same end-points and results as above

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

No panty liner Studies on ultra-thin menstrual pads (longer but with analogous construction to panty liners) Europe (Munich, Germany, late Ultra-thin test pad (perforated 10 Ultra-thin menstrual pad with panty shields vs. conventional summer through early spring) lm topsheet) thick pad Commercially available, competitive thick pad (non-woven topsheet)

30

118

124

11

Ultra-thin menstrual pad with panty shields vs. conventional thick pad (Japanese products)

North Americac (Midwest, late fall to early spring)

Ultra-thin test pad (perforated lm topsheet)

46

Marketed thick pad (perforated lm topsheet) 12 Ultra-thin menstrual pad with panty shields vs. conventional thick pad North America (Midwest, late spring through summer) Baseline phase (all subjects)

43 84 1 cycle (ad lib for menstrual protection)

Procter & Gamble, unpublished data, October 1989 Gynecological exam: no adverse effects Dermatological assessment: no signicant difference between groups or relative to baseline phase Vaginal and vulvar microbiology: no signicant difference in isolation frequencies or cell densities at any time point

Commercially available, competitive thick pad (non-woven topsheet) Prospective phase (randomized groups) 38 2 cycles (menstrual and daily, inter-menstrual use)

Ultra-thin test pad (perforated lm topsheet)

Marketed thick pad (perforated lm topsheet) 13 Ultra-thin menstrual pad with panty shields vs. conventional thick pad North America (Midwest, summer through mid-fall) Baseline phase (all subjects)

46 129 1 cycle (menstrual use)

Perineal skin wetness: during menstruation, skin wetness in prospective phase was lower than during baseline phase when pads had high uid content Procter & Gamble, unpublished data, January 1990 Gynecological exam: no adverse effects Dermatological assessment: slight erythema in a minority of subjects during baseline phase. Incidence declined in both groups during prospective phase Vaginal and vulvar microbiology: no signicant difference in isolation frequencies or cell densities between groups or relative to baseline phase Perineal skin wetness: during menstruation, skin wetness in prospective phase was lower than during baseline phase when pads had high uid content Procter & Gamble, unpublished data, March 1991

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

Commercially available, competitive thick pad (non-woven topsheet)

Prospective phase (randomized groups)

66

3 cycles (menstrual and daily, inter-menstrual use)

Ultra-thin test pad (perforated lm topsheet)

Marketed thick pad (perforated lm topsheet)

a b c

63

Some studies previously summarized in [35]. Number of menstrual cycles. Cultural barriers to the requisite clinical examinations necessitated testing of Japanese products by Western women.

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M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

3.3. Risk of urinary tract infections (UTIs) It has been suggested that pads and panty liners may increase the risk of UTIs by transferring intestinal ora such as E. coli to the vulva. Pads may promote some degree of transfer from the perianal region to the genitalia: for example, enteric bacteria are isolated more frequently from the vagina in pad users than in tampon users [24]. However, enteric microbes often reside on the perineum and labia majora in the absence of introital or peri-urethral colonization. These organisms are constituents of the endogenous genital ora: their mere presence at any site is not a risk factor for infection [2527]. The most important risk factor for recurrent UTIs in women of reproductive age is sexual intercourse [28,29], which, among other pathogenic mechanisms, promotes colonization of the introitus and urethra with uropathogenic E. coli in susceptible women [25,30]. The bladder may serve as a reservoir for recurrent infection [31,32]. Genetic, anatomical, hormonal, and immune factors also inuence individual susceptibility to this disease [3234].

scoring of the condition of the skin of the genitalia using standard numerical scales for erythema, moisture and dryness; vaginal and vulvar sampling for determining the isolation frequencies and cell densities of selected vaginal and vulvar microbes (e.g. lactobacilli, G. vaginalis, Candida species, Group B streptococci, enteric microbes, S. aureus); and participants subjective assessments of irritation, comfort, dryness, and product preference (Fig. 2). Some of these trials have been described in a previous review [35]. The trials assessed several variables:  Daily inter-menstrual panty liner wear for 16 menstrual cycles (Studies 1, 3, 4 and 79).  Combined menstrual pad and panty liner use in adult (Studies 5 and 6) and adolescent women (Study 2).  Up to three cycles of daily menstrual and inter-menstrual wear of ultra-thin menstrual pads that are longer, but otherwise analogous in construction to thin, superabsorbent panty liners (Studies 1013).  Scented and unscented panty liners (Studies 1, 5, and 7).  Ultra-thin pads with side panty shields, used intermenstrually as panty liners (Studies 1013).  Panty liners with novel materials, including a hybrid lm/ non-woven topsheet, a breathable backsheet, and odorabsorbing additives (Study 9). Studies were performed in various geographies and during different seasons. North American trials were conducted in the temperate Midwest in late spring through mid-summer, summer through early fall, and later fall through winter, depending on the study (Table 1). In Europe, studies were conducted in Mediterranean and temperate climates. Study 6 (Athens, Greece) and Study 8 (Paris, France) ran from spring to early summer; Study 10 (Munich, Germany) ran from late summer through early spring; Study 9 (Caracas, Venezuela) reects the cool subtropical climate of its location. These trials demonstrated no product-related adverse effects on gynecological health, skin condition, or the populations of potentially pathogenic genital microbes. A limitation of the clinical database is the lack of studies in Asia, the Middle East and Africa. In some regions, cultural norms inhibit participation in trials that require examinations of an intimate nature: Study 11 on Japanese pads was performed in North America because of such constraints (Table 1). In an attempt to overcome these limitations, trials performed under a range of climactic conditions are analyzed with reference to diary usage data documenting cycle length, duration of ow and number of pads worn per day. Similarities in climate and menstrual practices provide a measure of support for extrapolating from this database to other regions. Studies are underway in other world regions. A prospective sanitary pad trial recently performed in Nigeria relied primarily on subjective reporting of sensory irritation and comfort during wear to circumvent cultural barriers to vulvar examination [38]. The possible use of questionnaires

4. Toxicological and clinical evidence for panty liner safety The pre-market safety evaluation of pads and panty liners has been reviewed previously [35]. As a rst step, the potential health effects of each panty liner component are evaluated by quantitative risk assessment, an exposurebased approach for determining the health risks of chemicals with dose-dependent effects [36]. The most pertinent health effects assessed in this manner are the potential for skin irritation, the induction of delayed contact hypersensitivity, and acute or systemic effects. Because some regions of the vulva may be more permeable than skin at other sites, a conservative approach is employed when estimating percutaneous exposures to product ingredients [37]. In general, the ingredients used in panty liners have inert toxicological proles and a long history of safe use. The pre-market safety evaluation may also include studies to assess panty liner safety under practical conditions of use. Short-term investigations of panty liner effects on skin temperature and skin humidity were described earlier. Beyond these investigative studies, the safety of panty liners is supported by a series of 13 prospective, randomized clinical trials performed in North America, Europe, and Latin America between 1981 and 2005 (Table 1). These examiner-blind trials, all approved by Institutional Review Boards, utilized independent physicians in Obstetrics and Gynecology or Dermatology as study investigators. The protocols, developed with the help of academic and medical experts, employed either representative or exaggerated conditions of wear to address a range of usage practices. Depending on study objectives, clinical assessments included comprehensive gynecological examinations; visual

M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819

17

Fig. 2. Assessments performed in prospective clinical trials of pads and panty liners. Adapted with permission from ref. [35].

to assess signs and symptoms of infection will require careful validation. Another limitation is that the randomized trials reviewed herein recruited presumptively healthy women and did not specically assess subpopulations of women who may be predisposed to genital infection. Subgroups of women with a history of genital infections presently are included in prospective trials [39]. Future analyses of dened subpopulations may provide insight on the effects of panty liners in women who may be predisposed to infection due to host factors (e.g. women with bacterial vaginosis or recurrent VVC); or due to behavioral factors (e.g. sexual practices, IUDs or non-barrier contraceptive choices, douching, etc.). Emerging culture-independent methods such as PCR now are being applied to the study of endogenous [40] and pathogenic vulvovaginal microora [41,42]. Such techniques may improve our ability to assess genetic, behavioral and product-related changes in genital microbes.

Besides the aforementioned series of prospective trials, evidence from vulvar clinics indicates that panty liners are not a major contributor to persistent vulvar discomfort. Persistent vulvar symptoms (itch, soreness) found to be linked to exogenous causes most commonly resulted from irritation or contact sensitization either to vulvar medicaments or to the preservatives and perfumes in topical cleansing products [4345]. A few sensitization cases were linked to rubber condoms or dyes in underwear [43,44]. Studies that included diagnostic patch testing to panty liners failed to implicate these products [43]. Finally, most manufacturers employ post-market surveillance systems to monitor consumers experience and satisfaction. Though panty liner use is widespread, productrelated adverse events are rare. Statistics on absorbent hygiene products from 1997 to 1999 from the IKW, the German Cosmetic, Toiletry, Perfumery and Detergent Association (Industrieverband Koerperpege- und Waschmittel e.V.), revealed no medically conrmed case of allergic

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M. Farage et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 132 (2007) 819 [5] Runeman B, Rybo G, Forsgren-Brusk U, Larko O, Larsson P, Faergemann J. The vulvar skin microenvironment: impact of tight-tting underwear on microclimate, pH and microora. Acta Derm Venereol 2005;85(2):11822. [6] Schafer P, Bewick-Sonntag C, Capri MG, Berardesca E. Physiological changes in skin barrier function in relation to occlusion level, exposure time and climatic conditions. Skin Pharmacol Appl Skin Physiol 2002;15(1):719. [7] Launay JC, Besnard Y, Sendowski I, Guinet A, Hanniquet AM, Savourey G. Anthropological and thermoregulatory changes induced by a survival sojourn in a tropical climate. Wilderness Environ Med 2002;13(1):511. [8] Weydahl A, Halberg F. Daily spot-checking versus chronobiologic monitoring of human differential surface (rib versus breast) temperature. Prog Clin Biol Res 1987;227A:48391. [9] Booth G, Strang JM. Changes in temperature of the skin following ingestion of food. Arch Intern Med 1936;57:53343. [10] Hardy JD, DuBois EF. Basal metabolism, radiation, convection and vaporization at temperatures of 22 to 35 8C. J Nutr 1938;15:47797. [11] Hardy JD, DuBois EF. Differences between men and women in their response to heat and cold. Proc Natl Acad Sci USA 1940;256:38998. [12] Runeman B, Rybo G, Forsgren-Brusk U, Larko O, Larsson P, Faergemann J. The vulvar skin microenvironment: inuence of different panty liners on temperature, pH and microora. Acta Derm Venereol 2004;84(4):27784. [13] Farage MA, Enane N, Baldwin S, et al. Labial and vaginal microbiology: effects of extended panty liner use. Infect Dis Obstet Gynecol 1997;5:2528. [14] Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a casecontrol study among university students. Epidemiology 1996;7(2):1827. [15] Foxman B. The epidemiology of vulvovaginal candidiasis: risk factors. Am J Public Health 1990;80(3):32931. [16] Elegbe IA, Elegbe I. Quantitative relationships of Candida albicans infections and dressing patterns in Nigerian women. Am J Public Health 1983;73(4):4502. [17] Otero L, Palacio V, Carreno F, Mendez FJ, Vazquez F. Vulvovaginal candidiasis in female sex workers. Int J STD AIDS 1998;9(9):52630. [18] Mardh PA, Novikova N, Stukalova E. Colonisation of extragenital sites by Candida in women with recurrent vulvovaginal candidosis. BJOG 2003;110(10):9347. [19] Patel DA, Gillespie B, Sobel JD, et al. Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am J Obstet Gynecol 2004;190(3):64453. [20] Berg AO, Heidrich FE, Fihn SD, et al. Establishing the cause of genitourinary symptoms in women in a family practice. Comparison of clinical examination and comprehensive microbiology. JAMA 1984;251(5):6205. [21] Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK. Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm. Obstet Gynecol 1998;92(5):75765. [22] Hellberg D, Zdolsek B, Nilsson S, Mardh PA. Sexual behavior of women with repeated episodes of vulvovaginal candidiasis. Eur J Epidemiol 1995;11(5):5759. [23] Spinillo A, Pizzoli G, Colonna L, Nicola S, De Seta F, Guaschino S. Epidemiologic characteristics of women with idiopathic recurrent vulvovaginal candidiasis. Obstet Gynecol 1993;81(5 Pt 1):7217. [24] Watt B, Goldacre MJ, Loudon N, Annat DJ, Harris RI, Vessey MP. Prevalence of bacteria in the vagina of normal young women. Br J Obstet Gynaecol 1981;88(6):58895. [25] Stamey TA, Sexton CC. The role of vaginal colonization with enterobacteriaceae in recurrent urinary infections. J Urol 1975;113(2):2147. [26] Stapleton A, Hooton TM, Fennell C, Roberts PL, Stamm WE. Effect of secretor status on vaginal and rectal colonization with mbriated Escherichia coli in women with and without recurrent urinary tract infection. J Infect Dis 1995;171(3):71720.

contact dermatitis and less than one case of low-grade skin irritation per 9 million products sold (unpublished European industry data). In summary, while no category of personal products is completely devoid of minor complaints of irritation or discomfort, the results of pre-market safety assessment studies, data from vulvar clinics, evidence from post-market surveillance programs, and the widespread safe use of panty liners worldwide are a testimony to their safety.

5. Conclusion Panty liners are used to absorb light menstrual ow, urine or vaginal discharge and to maintain a clean, dry feeling. Allegations that panty liners may trap heat and moisture to promote VVC or promote colonization with microbes associated with UTIs appear unfounded. Scientic measurements of the impact of panty liners on skin temperature and skin surface moisture demonstrated that their effects have no meaningful clinical impact on the densities of genital microora. Epidemiological investigations of a potential link to infection were either negative or were inconclusive because of confounding factors. Most notably, a series of 13 randomized, prospective trials of panty liners or ultra-thin pads, under a variety of use conditions, have demonstrated no clinically signicant adverse effects on skin or on microora associated with common vulvovaginal infections. Taken together, the scientic evidence supports the conclusion that panty liners are safe for their intended use and do not promote adverse skin effects or common genital infections.

Acknowledgments The authors are grateful to Drs. K.W. Miller, K. Mesuere and B.E. Jones for the critical review of this manuscript. We thank Deborah Hutchins, Ph.D., of Hutchins & Associates, LL, Cincinnati, OH, USA, for technical input on the manuscript.

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