A Real Need:

Vaginal Moisturizers for Urogenital Atrophy

5/13/12

Ma Virginia M Santos-Abalos MD style FPSGE Click to edit Master subtitle FPOGS Professor, Cebu Institute of Medicine, CDU College of

Disclosure

Advisory Board / Speaker

Abbott Solvay Philippines Smith Kline

Bayer

Biofemme Glaxo MSD

Philippines
5/13/12

Nycomed

FACTS
Threats to Altered Vaginal Health normal 1 vaginal Increased risk for infections (BV) health at any stage 2 Likelihood of adverse pregnancy outcome of a womans 3 Poor quality of life in the peri- and life
4

menopausal years, and during chemotherapy for breast CA Impaired sexual function
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GENITOURINARY Tract

Embryologically and anatomically in close proximity Presence of estrogen receptors in the mucosa Pathophysiology in one produces symptoms in adjacent
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Discussion Points
Burden of the disease Estrogen and vaginal health

Practical management options for women presenting with vaginal dryness

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Burden of the Disease

How common is vaginal dryness? Does this cause significant suffering?

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Vulvovaginal Atrophy can occur at any time in a womans life cycle

Hypoestrogenic state

Postmenopause Lactation Hypothalamic amenorrhea Various breast cancer treatments

Drug-induced

Certain medications e.g antihistamines

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Atrophy increased significantly with increase Prevalence of superficial dyspareunia in menopausal age (p <0 by menopausal age and vulvovaginal atrophy .001)

Perimenopau se (n = 133)

01 23 4 year years years (n = (n = 39) (n = 52) 67) 5/13/12 J 2001;12:10710 Adapted from Versi E, et al. Int Urogynecol

Vaginal dryness with menopausesignificantly in Dryness increased

late perimenopause and postmenopause

(p <0 .001)

47%

32% 25% 21%

3%

4%

Premenopa use (n = 172)

Early perimenop ause (n = 148)

Late perimenop ause (n = 106)

PostPostPostmenopa menopa menopa use use use 1 year 2 years 3 years 5/13/12 Dennerstein L, et al. Obstet Gynecol(n = 31) 2000;96:3518 (n = 72) (n = 54)

Prevalence of superficial dyspareunia and vulvovaginal atrophy by menopausal age

Atrophy increased significantly with increase in menopausal age (p <0 .001)

Perimenopau se (n = 133)

01 year (n = 52)

23 4 years years 5/13/12 (n = 39) (n = Adapted from Versi E, et al. Int Urogynecol J 2001;12:10710 67)

Vaginal Dryness, a troublesome nuisance . . . . .

May be progressive in the absence of treatment

Superficial vulvovaginal fissures and petechiae Due to thinner and more fragile vaginal epithelium
Can affect everything from everyday comfort to ones sex life
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Lower estrogen levels are associated VAGINAL ATROPHY: Symptoms

6 0 5 0 4 0 % Reporting problems 3 0 2 0 1 0 0

Santiago Palacios. MATURITAS 63 (2009) 315-318 problems with increased prevalence of sexual
<184 pmol/l (50pg/ml) estradiol >184 pmol/l (50pg/ml) estradiol

Vaginal Bothered dryness by problem n = 93; significance not

reported

Vaginal dryness

Bothered Dyspareun Pain with Bur by ia penetrati ning Dyspareunia problem (intensity) on Sarrel PM. J Womens Health Gend Based Med 2000;9:S2532

Adapted from Sarrel PM. Obstet Gynecol 1990;75(4 Suppl):2630S 5/13/12 Santiago Palacios. MATURITAS 63 (2009) 315-318

Pain with penetratio Burning n

Click

icon 40% of Up toto add picture postmenopausal women experience vaginal atrophy

Only 25% of them seek medical assistance

Prevalence of vaginal atrophy

Bachman GA, et al. Am Fam Physician 2000;61:30906 5/13/12 Cardozo L, et al. Obstet Gynecol 1998;92:7227

Estrogen Deficiency: SYMPTOMS

Short term Medium Medium term term Long term
Menstrual irregularities Vasomotor disturbances Hot flushes, sweats, palpitations Irritability, mood swings Fatigue, depression Decreased libido Decreased libido Atrophic vaginitis Atrophic vaginitis Dyspareunia Dyspareunia UTI UTI Bone loss, osteoporotic fractures Cardiovascualr disease
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Vaginal Atrophy

Unlike vasomotor symptoms, which typically resolve over time, vaginal atrophy remains a persistent consequence of the menopausal transition and frequently requires treatment

International Menopause Society Writing Group. 5/13/12 Recommendations for the management of

Prevalence of symptoms in women treated for breast cancer

Menopause Rating Scale; n = 200
Symptom Hot flushes/sweats Sexual problems Urinary problems Vaginal dryness Symptoms (%) 85 60 55 55 Moderate severe (%) 63 45 39 34
Gupta P, et al. Climacteric 2006;9:4958

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Other UROGENITAL COMPLAINTS

1 2 3 4 5

Frequency Nocturia Urgency Incontinence Urinary tract infections

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Discussion Points
To review the physiology of the vulvovagina, with emphasis on factors maintaining vaginal health. To list symptoms and conditions associated with altered vaginal health.

To identify practical management options for women presenting with vaginal dryness.

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EXTERNAL GENITAL Gross Anatomy ORGANS

-MONS PUBIS -CLITORIS -URINARY MEATUS -LABIA MAJORA -LABIA MINORA BARTHOLIN S GLAND PERIURETHR AL GLANDS
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Vaginal Maturation Index

Evaluate effects of estrogen on vaginal tissue Office procedure MI = 10/30/60 10% parabasal cells, 30% intermediate cells 60% superficial cells A shift to the left is associated with vaginal atrophy 5/13/12 Nilsson K, et al. Maturitas 1995;21:51-56

Estrogen & Vaginal Health

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Superficial Intermediate Parabasal Metaplastic

S P

I M

Vaginal Cell Maturation

MI = 10/30/60

10% Parabasal 30% Intermediate 5/13/12 60% Superficial

Effects of estrogen on the vaginal epithelium

Mucus layer Glycogen formation Dderlein's lactobacilli convert glycogen from sloughed vaginal cells

Lactic acid

Vaginal pH (3.5-4.5)

Estrogen

Maintains thickness of squamous vaginal epithelium, rugae, pink color, and moisture

Protects from: Streptococcus Staphylococcus Coliform Diphtheroid infections

Proliferation of connective tissue Fragmentation of elastin Hyalanization of collagen

IMS Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010

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Normal Vaginal Physiology

ESTROGEN, the key hormone, maintains lactobacilli dominance and vaginal pH 3.8-4.5. Estrogen ensures sufficient cellular glycogen for the lactobacilli. The period before, during, and after menopause is as hormonally tumultuous as it is during the childbearing years, if not more.
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WELL-ESTROGENIZED VAGINA

Normal Introitus

Layers well5/13/12 delineated

Gross Changes with Estrogen Loss

Changes in vaginal secretions, decrease in moisture content Loss of dermal collagen and adipose Shortening, narrowing of the vaginal canal; adhesions develop between touching surfaces Vaginal walls thinner, less elastic, pale, with loss of rugae Mucosal inflammation and petechiae, ulcerations, bleeding often after minimal trauma

Mehta A, Bachmann G. Vulvovaginal complaints. Clin Obstet Gynecol. 2008;51:549-555

Atrophy Of Labia Majora 5/13/12 Low Moisture Content

Gross Changes with Estrogen Loss

Loss of labial and vulvar fullness Pallor of urethral & vaginal epithelium Minimal vaginal moisture

Mehta A, Bachmann G. Vulvovaginal complaints. Clin Obstet Gynecol. 2008;51:549-555

Loss of urethral meatal turgor

Atrophy Of Labia Majora 5/13/12 Low Moisture Content

Gross Changes with Estrogen Loss

Mehta A, Bachmann G. Vulvovaginal complaints. Clin Obstet Gynecol. 2008;51:549-555

Atrophy of the prepuce of the clitoris, hence, more easily irritated Decreased dermal collagen content in the urethral mucosa Reduction of urethral vascular flow diminishes sensitivity of the urethral musculature to adrenergic stimulation.
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Estrogen and Physical Changes

Normal vulvovagina Vaginal Atrophy

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ESTROGEN and Histologic changes

WELL-ESTROGENIZED

ESTROGEN LOSS

NORMA
Multi-layered w/ good blood supply Superficial cells rich in glycogen Atrophy with marked thinning of the epithelium Reduced blood supply Loss of 5/13/12 glycogen

Vaginal histology
H & E, magnification 10

Premenopause Well-estrogenized epithelium, multi-layered with good blood supply; superficial cells rich in glycogen

Postmenopause Estrogen-deficiency atrophy with marked thinning of the epithelium, reduced blood supply and loss of glycogen 5/13/12

Postmenopausal changes in the vaginal epithelium

PREMENOPAUSAL
Erectile tissue Folds or rugae Muscular coat Inner lining contains large amount glycogen

POSTMENOPAUSAL

Loss of folds Loss of inner lining and glandular function

Samsioe G. A profile of the Menopause, 1995:49 (Figure 6.4)

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Clinical Assessment of the Vagina

Adapted with permission from Parsons A, et al. Obstet Gynecol. 2003

DEGREE RUGAE PALLOR

MILD
Reduced Light pink

MODERATE
Rare Pale Bleeds on scraping None

SEVERE
Smooth vagina White / deep red Bleeds on contact Stenosis

PETECCHIA Rare E MUCOSAL Decreased ELASTICITY DRYNESS VAGINAL pH

Slightly decreased >4.5 <5

Minimal 5&>

Dry >5

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THREATS to the vaginal ecosystem

ESTROGEN GLYCOGEN LACTOBACILLI LACTIC ACID pH 3.8-4.5
HORMONE CHANGES Diabetes Oral Contraceptive Pills Aromatase Inhibitors (AI) ANTI-MICROBIALS MENSES SEMEN SOAP pH= 8 pH= 7-10
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Acid vaginal pH Vaginal pH, predictor of a protective mechanism for RTI, UTI status of vaginal ecosysytem
Correlates with decreased risk for RTIs (Chlamydia and Trichomonas), as well as UTI. (Bosket et al. Infect Immuno 1999) Increases lactobacilli ability to bind to the vaginal epithelium Reduces the activity of pathogenic bacterial enzymes such as sialidase. (Nagy et al. BJOG 1985) Protective against BV, mycoplasma hominis, bacteroides;maximum attachment of Gardnerella to vaginal cells at alkaline pH 5-6. (Cauci et al. AJOG) (Sobel JD. BV., Annu Rev Med 2000)

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Vaginal ph and Maturation Index

Surrogate markers of vaginal health

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ESTROGEN DEFICIENCY And VULVOVAGINAL HEALTH

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ESTROGEN DEFICIENCY
1. 2. 3. 4. 5.

Vaginal dryness (27-55%) Vulvar / vaginal soreness Dyspareunia (40%) Recurrent UTI Predisposition to RTI
Palacios Santiago. MATURITAS 63 5/13/12 (2009) 315-318

ATROPHIC VAGINITIS

predominantly parabasal cells

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Altered vaginal health, a fact of life for every woman at some point
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CASE CHALLENGE on vaginal dryness

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A distressed, sexually active, 55y/o G4P4 consults because of vaginal itching and soreness . . . . .

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A distressed, sexually active, 55y/o G4P4 consults because of vaginal itching and soreness . . . . .
Douches post-intimacy Daily intake of antihistamines for allergic rhinitis Vaginal soreness, pain during intercourse

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A distressed, sexually active, 55y/o G4P4 consults because of vaginal itching and tingling sensation . . . . .
BMI=25 General PE: unremarkable Pelvic Exam: parous outlet; atrophic labia majora absent vaginal rugae deep red vaginal walls with some fissures smooth pale cervix, small uterus, adnexae (-) poor pelvic support
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QUESTION: Is this vaginal dryness itching or vaginal infection itching?

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Vaginal infections almost always include some discharge characteristic of which depends on the offending organism.

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Vaginal Dryness Itching

There is NO DISCHARGE.
The main component that makes vaginal dryness uncomfortable and itchy is the LACK /
LOSS of MOISTURE.
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Considering the patients profile, the loss of estrogen contributed primarily to the symptoms.

Post-intimacy douching (?) Antihistamine use (?)

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Management Options

Estrogen Therapy Lifestyle & Behavioral modification Non-Hormonal therapy

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Estrogen and Vaginal Atrophy Research has shown that low-dose vaginal estrogen is effective and well tolerated for treating vaginal atrophy and has been shown to reduce vaginal symptoms, including dyspareunia and vaginal dryness, and to restore vaginal pH and normal vaginal cytology

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Estrogen therapy reverses atrophy

Huang, Kaley. Gender-specific regulation of CV function: Estrogen as key player. Microcirculation 2004; 11 (Jan-Feb (1): 938) Johnston, Farrell, Bouchard, Beckerson, Comeau, Lefebvre, Papaioannou. SOGC Joint Com-CPG Gynecology and Urogynecology. Detection and Management of Urogenital Atrophy. J Obstet Gynec Canada 2004; 26 May (5): 503-15) Suckling, Lethaby, Kennedy. Local Estrogen for vaginal atrophy in 5/13/12 Postmenopausal Women. Cochrane Database 2006;

LOW DOSE TOPICAL ESTROGENS

(3-6 months therapy) 63 (2009) Advantages S Palacios. MATURITAS

Avoid enterohepatic circulation No or minimal endometrial stimulation Progestogens not required Minimal side effects Exerts mainly local effects No systemic effects Mode of administration not acceptable for some women
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Disadvantages

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LOW DOSE TOPICAL ESTROGENS (3-6 months therapy) S Palacios. MATURITAS

63 (2009)

ADVANTAGES -avoid enterohepatic circulation -lowest possible dose -no or minimal endometrial stimulation -progestogens not required -minimal side effects -exerts mainly local effects DISADVANTAGES -no systemic effects -mode of administration not acceptable for some women 5/13/12

UROGENITAL ATROPHY: EFFECTS of ESTROGEN THERAPY

ESTROGEN THERAPY

Activation of estrogen receptors Increase in vaginal secretions Epithelial proliferation, vascularization and increased blood flow velocity Glycogen deposition Higher lactic acid production Low vaginal pH 5/13/12

Menopausal using systemic women Many women suffering fromurogenital HRT still suffer Atrophic Vaginitis symptoms

Women with Systemic HRT Women without systemic HRT

Notelovitz M et al. Obstetrics

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Menopausal women suffering from atrophic vaginitis

Physicians perspective: Women without systemic HRT Women with systemic HRT

Patients suffering from atrophic vaginitis Patients not suffering from atrophic vaginitis 39% 61%

27% 73%

Over half of postmenopausal women will have urogenital discomfort associated with estrogen deficiency Although many women use oral hormone replacement therapy, urogenital symptoms persist
Notelovitz M, et al. Obstet Gynecol 2002;99:556 62

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Postmenopausal Vaginal Atrophy

IMS recommendations Climacteric 2011 SOGC Clinical Practice Guidelines. J Obstet Gynaecol Can 2004

Detection & Health-care providers should routinely assess diagnosis postmenopausal women for the symptoms and signs

of vaginal atrophy, a common condition that exerts significant negative effects on quality of life. (III-C)
General Treatment

1Should be started early and before irrevocable

atrophic changes have occurred

2Needs to be continued to maintain the benefits

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Postmenopausal Vaginal Atrophy

Estrogen Therapy
IMS recommendations Climacteric 2011 SOGC Clinical Practice Guidelines. J Obstet Gynaecol Can 2004

1All local estrogen preparations are effective and

patient preference will usually determine the treatment used

2All currently available topical estrogens are absorbed,

the extent depending on dose and formulation.

3Although systemic absorption of estrogen can occur

with local preparations, there is insufficient data to recommend annual endometrial surveillance in asymptomatic women using local estrogens. (III-C)

4Additional progestogen is not indicated when

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appropriate low-dose, local estrogen is used although long-term data (>1 year) are lacking.

Postmenopausal Vaginal Atrophy

IMS recommendations Climacteric 2011 SOGC Clinical Practice Guidelines. J Obstet Gynaecol Can 2004

If Estrogen ineffective or undesired Gynecological hormoneresponsive cancers

Vaginal lubricants and moisturizers can relieve symptoms due to dryness 1 Few data on the use of vaginal estrogens so they should be used with discretion

2 Use of local estrogen in women on tamoxifen or aromatase inhibitors needs careful counselling and discussion with the patient and the oncology team.

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Vaginal Atrophy & Estrogens

However, given the fear many women have of estrogens, there is a motivation to explore alternative therapies.
Winneker RC. Progress and Prospects in Treating 5/13/12 Postmenopausal Vaginal atrophy.

Are there practical strategies to maintain vaginal moisture?

Behavioral Modification Advantage

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OPTIONS for maintaining Vaginal Moisture

Diet Tofu, phytoestrogen

Hydration Key for maintaining moist mucous membranes of the body Caffeine and alcohol have a diuretic (dehydrating) effect, that can be more pronounced in some women Women in perimenopause and menopause may have more difficulty clearing the body of these substances, and overconsumption of either particularly alcohol can exacerbate vaginal dryness
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OPTIONS for maintaining Vaginal Moisture

Medications/ Chemicals that may aggravate vaginal dryness Regulate intake of medications for allergies eg. antihistamine not only dry up sinuses, but vaginal secretions as well.

Chemically-enhanced feminine products / douching: can cause vaginal dryness by disrupting the delicate natural chemical balance of the vagina

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OPTIONS for maintaining Vaginal Moisture

Natural Strategies Kegel exercises help increase circulation to the pelvic area to keep vaginal tissue healthy and strong. Regular sexual activity should be encouraged to protect against urogenital atrophy, presumably by increasing the blood flow to the pelvic organs. (II-2B)
Leiblum S, et al.Vaginal atrophy in the postmenopausal woman: the importance of sexual activity and hormones. JAMA 1983

5/13/12 SOGC Clinical Practice Guidelines. J Obstet

Vaginal Atrophy in the Postmenopausal Woman

The Importance of Sexual Activity and Hormones

n= 52 Sexually active: 3/mo Sexually inactive: <10/yr Index of genital atrophy Blood samples: estrone estradiol androstenedionet estosterone FSH, LH

Less vaginal atrophy was apparent in the sexually active women as opposed to the sexually inactive women Women with less vaginal atrophy had significantly higher mean levels of androgens (androstenedione and testosterone) and gonadotropins (particularly LH).

Leiblum S, et

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Will non-hormonal therapy work?

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Non-HORMONAL Therapy
2007

Modified from NAMS. Menopause Practice: A Clinician's Guide, 3rd edition. Cleveland, OH: The North American Menopause Society;

Composition Waterbased vaginal lubricants

Therapeutic Relevance Use limited to ease penetration during intercourse

Vitamin E oil Eases penetration during sexual intercourse and may relieve itching, irritation

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Non-HORMONAL Therapy
2007

Modified from NAMS. Menopause Practice: A Clinician's Guide, 3rd edition. Cleveland, OH: The North American Menopause Society;

Composition

Therapeutic Relevance

Replenish and maintain water content in Vaginal moisturizer the vagina to relieve irritation, itching, and burning Not limited to sexual exchange Vaginal gel Acidifies vaginal pH, reduces minor vaginal irritations and odors; may be used after intercourse and/or uterine bleeding
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Non-HORMONAL Therapy
Modified from NAMS. Menopause Practice: A Clinician's Guide, 3rd edition. Cleveland, OH: The North American Menopause Society;

2007

Composition Vaginal lubricants

Therapeutic Relevance
1

Eases penetration during sexual intercourse Water-based, water-soluble, and slightly acidic (pH balanced) preferred. Petroleum products not recommended. This slight acidity inhibits the growth of harmful microorganisms, yeast. No long term therapeutic effect
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Vaginal Moisturizers
Vaginal moisturizers applied on a regular basis have an efficacy equivalent to local hormone replacement for the treatment of local urogenital symptoms such as vaginal itching, irritation, and dyspareunia, and should be offered to women wishing to avoid use of 5/13/12 SOGC Clinical Practice Guidelines. J Obstet hormone replacement therapy.

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polycarbophil bisabolol LACTIC ACID vaginal MOISTURIZING GEL

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Polycarbophil-Bisabolol Lactic Acid Vaginal gel

Poly carbophil
1Bioadhesive polymer in gel form

Draws water out of the cells into the vagina Prevents volatilization of amines Promotes restoration of lactobacilli and acidifies vaginal pH

2A weak polyacid ph=2.8

Its large molecule is neither absorbed nor immunogenic.

3 With its multiple carboxyl radicals, it adheres to the

vaginal epithelial cells until they turn over (3-5 days) and buffers vaginal secretions Cells regain natural elasticity and moisture Promotes healing of tissues.
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Polycarbophil-Bisabolol Lactic Acid Vaginal gel

-Bisabolol 1A Levomenol, a natural monocyclic sesquiterpene ROH
2Colorless

viscous oil, the primary constituent of the essential oil from German chamomile Almost insoluble in water and glycerin, well soluble in ethanol Has skin healing properties. Known to have anti-irritant, anti-inflammatory and anti-microbial properties.
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Polycarbophil-Bisabolol Lactic Acid Vaginal gel

LACTIC Acid
Acidifies vaginal pH Reduces minor vaginal irritations and odors May be used after intercourse and/or uterine bleeding

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STUDIES on EFFICACY and SAFETY

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Polycarbophil vs. local Estrogen in menopausal women

(Nachtigall LE. Fertil Steril Jan 1994)

Study

n= 30 >1year postmenopause, not on HRT, cancerfree and experiencing vaginal discomfort or dyspareunia. Polycarbophil gel 3x/week for 12weeks CEE cream 2g vaginally daily for 12weeks

Randomized

Parameters Pap smear, vaginal pH, MI index (baseline, week4, week8, week12)
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Polycarbophil vs. local Estrogen in menopausal women

(Nachtigall LE. Fertil Steril Jan 1994)

Results

1Both

had statistically significant return of vaginal moisture and vaginal fluid and premenopause pH levels by week 4 remained free of vaginal infections for the duration of the study have increased vaginal elasticity; Statistically significant in the estrogen group by week4 atrophy reversed at week12 in estrogen group.
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2Women

3Both

4Vaginal

Polycarbophil vs. local Estrogen in menopausal women

(Nachtigall LE. Fertil Steril Jan 1994)

Conclusion

Polycarbophil gel is safe and an effective alternative to estrogen vaginal cream in postmenopausal women with uncomfortable symptoms of vaginal dryness, exhibiting increases in vaginal elasticity with return to premenopausal pH state

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Polycarbophil versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women.(Bygdeman M, Swahn
ML. Maturitas 1996)

Study n= 39 Polycarbophil gel 3x/week for 12weeks Randomized Dienoestrol daily during the first 2 weeks and thereafter 3x a week Parameters Vaginal dryness index, itching, irritation, dyspareunia, pH and safety were evaluated every week the first month and every month thereafter.
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Polycarbophil vs. local Estrogen in menopausal women

(Nachtigall LE. Fertil Steril Jan 1994)

Results

1Both

treatments had a significant increase on vaginal dryness index as soon as the first week of treatment. Hormonal compound was significantly better than the non-hormonal one symptoms such as itching, irritation and dyspareunia significantly decreased or disappeared without any difference between the two treatments
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2All

Polycarbophil vs. local Estrogen in menopausal women

(Nachtigall LE. Fertil Steril Jan 1994)

Conclusion

Polycarbophil applied vaginally 3x a week, is a full therapy for all symptoms of vaginal atrophy as well as local estrogen. No serious adverse event was related. It is an alternative treatment to local estrogen and perhaps a good complement of systemic HRT in patient suffering from vaginal dryness.
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Effect on Vaginal pH of a polycarbophil vaginal gel compared with acidic douche in women with suspected BV
(Massimo M, Bruno M, Ilaria S. Current Therapeutic Research, Oct 2000)

Objective

To compare and assess the pH-lowering effect of polycarbophil with acidic vaginal douche

Controlled, Randomized n=30 (18-60 yo), vaginal pH>4.5 & suspected Blinded study BV (+ whiff test; + clue cells, gram stain score 4) Groups 6 weeks: Polycarbophil gel 2.5g Acidic vaginal douche 2x a week 5/13/12

Effect on Vaginal pH of a polycarbophil vaginal gel compared with acidic douche in women with suspected BV
(Massimo M, Bruno M, Ilaria S. Current Therapeutic Research, Oct 2000)

Outcomes Measured by Baseline, 3 wks, 6 wks investigator Vaginal pH, wet mount, KOH, Gram stain

Specimen obtained 8hrs after gel / douche use; day7 from LMP; 48hrs post-coital
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Effect on Vaginal pH of a polycarbophil vaginal gel compared with acidic douche in women with suspected BV
(Massimo M, Bruno M, Ilaria S. Current Therapeutic Research, Oct 2000)

acidic douche polycarbophi l

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Effect on Vaginal pH of a polycarbophil vaginal gel compared with acidic douche in women with suspected BV
(Massimo M, Bruno M, Ilaria S. Current Therapeutic Research, Oct 2000)

Results
Vaginal pH
Week 3 Week 6

Polycarbophil 4.7 (+/- 0.6) 4.6 (+/- 0.7)

Acidic Douche 5.4 +/- 0.5 pH 5.3 +/- 0.8

pH lowering effect of polycarbophil after single application is maintained up to 80 hrs Effect on BV Adverse effects Physical & microbiological signs of BV improved in the polycarbophil group No adverse effects noted in both groups 5/13/12

Effect on Vaginal pH of a polycarbophil vaginal gel compared with acidic douche in women with suspected BV
(Massimo M, Bruno M, Ilaria S. Current Therapeutic Research, Oct 2000)

Conclusions
Polycarbophil vaginal gel reduces vaginal pH to almost physiologic levels and reduces vaginal pH in women suspected of BV, compared with acidic vaginal douche. Polycarbophil may thus represent not only a way to reduce vaginal acidity and help maintain physiologic levels but may play an important role in preventing complications related to altered vaginal pH.
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Successful treatment of bacterial vaginosis with a policarbophil-carbopol acidic vaginal gel: results from a randomised double-blind, placebo-controlled trial.
Fiorilli A, Molteni B, Milani M. Eur J Obstet Gynec Repro Biol June 2005

Objective

To evaluate the efficacy of a mucoadhesive vaginal gel with acidic-buffering properties in bacterial vaginosis (BV). Double Blind Placebo-controlled 12-wk trial n=45 non-pregnant women with BV Polycarbophil-carbopol acidic gel 2.5g Placebo Treatment phase: Daily for 1 week then q3days for 5 wks Follow-up phase: Weekly follow-up without treatment 6 wks
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Design Groups

Successful treatment of bacterial vaginosis with a policarbophil-carbopol acidic vaginal gel: results from a randomised double-blind, placebo-controlled trial.
Fiorilli A, Molteni B, Milani M. Eur J Obstet Gynec Repro Biol June 2005

Clinical Cure rate

Absence of vaginal discharge, vaginal pH <4.5, (-) whiff test, Nugent score <7
Policarbophil
93% 86%

Clinical cure
Week 6 Week 12

Placebo
6% 8%

p value
0.0001 0.0001

Vaginal pH
Baseline Week 12

Policarbophil
6.1 +/- 0.7 4.3 +/- 0.3

Placebo
5.5 +/- 0.7 5.1 +/- 0.5
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Successful treatment of bacterial vaginosis with a policarbophil-carbopol acidic vaginal gel: results from a randomised double-blind, placebo-controlled trial.
Fiorilli A, Molteni B, Milani M. Eur J Obstet Gynec Repro Biol June 2005

Conclusion

Policarbophil-carbopol acidic vaginal gel is an effective treatment of bacterial vaginosis

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BV, detected in 20% of pregnant women

(Kurki et al Obstet Gynec 1992)

Preterm delivery complicates almost 9% of all pregnancies (Iams J 1998) BV is a known risk factor for preterm birth and low birthweight (Colli et al. J Int Med
1996).

BV and PREGNANCY OUTCOME

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Bacterial vaginosis increased IL-6 and vaginal ph >4.7, and is associated with obstetric complications
Lockwood CJ et al. Increased IL-6 in cervical secretions assocd with Preterm delivery. Am JOG 1994 Colli E et al. BV in pregnancy and Preterm Birth: Evidence from the literature. J Int Med Jul-Aug 1996 Iams J et al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. Am JOG 1998 Paternoster DM et al. Biochemical markers for prediction of spontaneou preterm birth. Int JGO 2002 5/13/12

Efficacy of an acidic vaginal gel on vaginal pH and IL-6 levels in low-risk pregnant women
(Paternoster DM, Tudor L, Milani M, Maggino T, Ambrosini A.. J Maternal-Fetal and Neonatal Med 2004)

Randomized double-blind, placebo-controlled trial Objective Method

To evaluate effects of an acid-buffering vaginal gel on vaginal pH and IL-6 levels in pregnant women n=70 low-risk pregnant women, singleton, 2d trimester Acidic vaginal gel 2.5 gm q3d X 12 weeks Placebo
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Efficacy of an acidic vaginal gel on vaginal pH and IL-6 levels in low-risk pregnant women
(Paternoster DM, Tudor L, Milani M, Maggino T, Ambrosini A.. J Maternal-Fetal and Neonatal Med 2004)

Objective: To evaluate effects of an acid-buffering vaginal gel on vaginal pH and IL-6 levels in pregnant women. >Randomized , double-blind, placebocontrolled trial

Background: Increased IL-6 and vaginal pH>4.7 associated with obstetric complications. Topical therapy to maintain physiologic vaginal pH could help in prevention of vaginal infections. Methods: 70 low risk pregnant women, singleton, 2nd trimester.

35 randomized to use acidic vaginal gel 2.5g q3 days x 12weeks, 35 to 5/13/12 placebo.

Efficacy of an acidic vaginal gel on vaginal pH and IL-6 levels in low-risk pregnant women
(Paternoster DM, Tudor L, Milani M, Maggino T, Ambrosini A.. J Maternal-Fetal and Neonatal Med 2004)

Vaginal pH
Acidic Gel Placebo

Baseline
4.6 +/- 0.4 4.4 +/- 0.3

After treatment
4.3 +/-0.3 4.3 +/-0.3

Normalized fr pH 4.7
10/14 1/8

p value
0.04 NS

IL-6
Acidic Gel Placebo

Baseline
12.0 7 9.0 5

After treatment
8.9 5* 13.5 + 6.8

Percent change
-36% +50%
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< 0.02 0.05

Conclusion

The use of the acidic gel in low-risk pregnant women is able to maintain a physiological vaginal ecosystem and prevents the increases of vaginal pH and vaginal IL6.
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Conclusion

Prospective and controlled trials are warranted to evaluate whether the acidic vaginal gel can reduce obstetric complications linked to vaginal inflammation during pregnancy.

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The effect of polycarbophil gel on bacterial vaginosis: a pilot study.

Wu JP, Fielding SL, Fiscella K. Eur J Obstet Gynec Repro Biol June 2007

OBJECTIVE: To determine if use of intravaginal polycarbophil gel for 1 month will: (1) lower vaginal pH (2) improve signs of bacterial vaginosis (BV).

STUDY DESIGN: 17 women with BV selfadministered polycarbophil gel every 3rd day for 4 weeks in an open-label, prospective pilot study. Primary outcome measures included vaginal pH, presence of amines and Nugent 5/13/12 scores.

The effect of polycarbophil gel on bacterial vaginosis: a pilot study.

Wu JP, Fielding SL, Fiscella K. Eur J Obstet Gynec Repro Biol June 2007

RESULTS:

At week 4, there was improvement in Nugent scores, vaginal odor and clue cell count (p<0.05). Eleven women converted from amine positive to negative (73+/-20%). There was no significant change in vaginal pH.

CONCLUSIONS: Polycarbophil gel is associated with improved signs of BV, although not vaginal pH.
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Bacterial vaginosis: an update on diagnosis and treatment.

Verstraelen H, Verhelst R. Department of Obstetrics & Gynaecology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. Expert Review Anti-Infective Therapy Nov 2009

Bacterial vaginosis, most common cause of vaginal complaints, is further associated with a sizeable burden of infectious complications. Diagnosis relies on standardized clinical criteria or on scoring bacterial cell morphotypes on a Gram-stained vaginal smear. Treatment remains cumbersome and clinicians are currently rather poorly armed to treat bacterial vaginosis in the long run. As an adjuvant to standard treatment with antibiotics, 5/13/12

Studies . . . . .

>reducing vaginal pH in suspected BV >decrease in vaginal pH and IL-6 >effective option for breast CA survivors
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GYNECOLOGIC MANAGEMENT OF SEXUAL PAIN FROM ATROPHIC VAGINITIS AND VAGINAL ATROPHY

Curr Oncology 2007 December; C. Derzko, MD,* S. Elliott, MD, and W. Lam, BSc(Pharm) MD

In view of recent findings raising concerns over elevated circulating estradiol levels (from 0-5pmol/l to 72pmol/l) in breast cancer patients on ai therapy who are using transvaginal estrogenic preparations,

5/13/12

GYNECOLOGIC MANAGEMENT OF SEXUAL PAIN FROM ATROPHIC VAGINITIS AND VAGINAL ATROPHY

Curr Oncology 2007 December; C. Derzko, MD,* S. Elliott, MD, and W. Lam, BSc(Pharm) MD

In view of recent findings raising concerns over elevated circulating estradiol levels in breast cancer patients on ai therapy who are using transvaginal estrogenic preparations, non-hormonal therapies including regular application of vaginal moisturizers and lubricants are recommended and certainly be first-line therapy. In addition, pelvic therapy for pelvic tone awareness and pelvic floor exercises (eg, Kegel exercises) and lifestyle modification are preferred 5/13/12

Practical Clinical Guidelines for Assessing and Managing Sexual Dysfunction and Atrophic Vaginitis after Breast CA
M. Hickey; C. Saunders; A. Partridge; N. Santoro; H. Joffe; V. Stearns. Annals of Oncology Oct 2008 19(10):1669-1680

Vaginal estradiol may reverse efficacy of aromatase inhibitors in suppressing estrogen. Estriol-containing preparations may be helpful, however, safety is still not established. When vaginal dryness is contributory, non-hormonal agents such as vaginal moisturizers (polycarbophilcontaining) may be effective for hypoactive sexual desire in these women. Testosterone therapy is offered by some 5/13/12 clinicians but its safety and efficacy have not

MANAGING UROGENITAL ATROPHY: A Review Palacios S. Maturitas

63 (2009) 315-18

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MANAGING UROGENITAL ATROPHY

Palacios S. Maturitas 63 (2009) 315-18

The review provides a practical guide on the diagnosis and management of UGA. A literature search done in MEDLINE (19692008) for original reports, meta-analysis and guidelines. 15% of premenopausal women and 40-57% of postmenopausal women have symptoms related to UGA. However, <25% receive medical care.
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MANAGING UROGENITAL ATROPHY

Palacios S. Maturitas 63 (2009) 315-18

contd . . . . . Lubricants are temporary measures to relieve vaginal dryness during intercourse, and moisturizers give longer symptomatic relief and has an effect on the vaginal epithelium maturity. Estrogen given systemically in all dosage regimens is effective, but topical therapy alone is preferred if systemic treatment is not needed. Treatment may be for long term as symptoms
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MANAGING UROGENITAL ATROPHY

Palacios S. Maturitas 63 (2009) 315-18

ESTROGEN THERAPY

2006 Cochrane systematic review of 19 good quality trials (4162 postmenopausal women randomized to different estrogen preparations for 3-6 months, and endpoints were efficacy, safety, acceptability; vaginal estradiol tablets more effective than the ring and clearly superior over placebo for symptom-relief). Meta-analysis by Cardozo et al showed superiority of estrogen over placebo, and that the vaginal route is linked to a better 5/13/12

Urogenital Health Update 2009 Conjugated estrogen cream, an intravaginal sustained-release estradiol ring, or estradiol vaginal tablets are recommended as effective treatment for vaginal atrophy. (IA)
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SUMMARY

Threats to normal vaginal health at any stage of a womans life Vaginal dryness associated with altered vaginal health is a concern but only a few seek medical care

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SUMMARY

Polycarbophil-containing vaginal moisturizers reduce vaginal ph and improves moisture content and is effective for relief of vaginal dryness. Initial studies of polycarbophil on maintaining acid vaginal ph and low IL-6 in low risk pregnant women seem promising and may be linked in the reduction of adverse pregnancy outcome. Polycarbophil vaginal gel can be offered for managing vaginal dryness in breast 5/13/12 CA patients.

VAGINAL DRYNESS, an emerging concern . . . . .

POLYCARBOPH IL- BISABOLOL LACTIC Acid containing vaginal gel, with its vaginal moisture elasticity, and pH- restoring properties, is a rational option.

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Vaginal Moisturizers:

a real need
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