Atrophic vaginitis: Difference between revisions
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*Cancer and precancerous lesions: [[vulvar intraepithelial neoplasia]], [[vulvar cancer]] and [[extramammary Paget disease]] | *Cancer and precancerous lesions: [[vulvar intraepithelial neoplasia]], [[vulvar cancer]] and [[extramammary Paget disease]] | ||
*Others: foreign body, sexual trauma and contact irritants | *Others: foreign body, sexual trauma and contact irritants | ||
The following is a list of differential diagnosis for Atrophic Vaginits: <ref name="pmid26125955">{{cite journal| author=Guerrero A, Venkatesan A| title=Inflammatory Vulvar Dermatoses. | journal=Clin Obstet Gynecol | year= 2015 | volume= 58 | issue= 3 | pages= 464-75 | pmid=26125955 | doi=10.1097/GRF.0000000000000125 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26125955 }} </ref><ref name=CDC-BV> Centers for Disease Control and Prevention. 2015 Sexually Transmitted Diseases Treatment Guidelines. Bacterial Vaginosis. http://www.cdc.gov/std/tg2015/bv.htm Accessed on October 13, 2016 </ref><ref name="pmid10839558">{{cite journal| author=Bachmann GA, Nevadunsky NS| title=Diagnosis and treatment of atrophic vaginitis. | journal=Am Fam Physician | year= 2000 | volume= 61 | issue= 10 | pages= 3090-6 | pmid=10839558 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10839558 }} </ref><ref name="pmid2448502">{{cite journal| author=Krieger JN, Tam MR, Stevens CE, Nielsen IO, Hale J, Kiviat NB et al.| title=Diagnosis of trichomoniasis. Comparison of conventional wet-mount examination with cytologic studies, cultures, and monoclonal antibody staining of direct specimens. | journal=JAMA | year= 1988 | volume= 259 | issue= 8 | pages= 1223-7 | pmid=2448502 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2448502 }} </ref><ref name="pmid21422855">{{cite journal| author=Sobel JD, Reichman O, Misra D, Yoo W| title=Prognosis and treatment of desquamative inflammatory vaginitis. | journal=Obstet Gynecol | year= 2011 | volume= 117 | issue= 4 | pages= 850-5 | pmid=21422855 | doi=10.1097/AOG.0b013e3182117c9e | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422855 }} </ref><ref name="pmid97946645">{{cite journal| author=Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK| title=Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm. | journal=Obstet Gynecol | year= 1998 | volume= 92 | issue= 5 | pages= 757-65 | pmid=9794664 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9794664 }}</ref> | |||
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*presence of [[Candida]] on wet mount (adding 10% KOH destroys the cellular elements and facilitates recognition of budding yeast, pseudohyphae, and hyphae) | *presence of [[Candida]] on wet mount (adding 10% KOH destroys the cellular elements and facilitates recognition of budding yeast, pseudohyphae, and hyphae) | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lichen | | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lichen Sclerosus]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
* | *Affects pre-pubertal and post-menopausal women, reflecting its nature of occurrence in low estrogen states<ref name="pmid23925660">{{cite journal| author=Zendell K, Edwards L| title=Lichen sclerosus with vaginal involvement: report of 2 cases and review of the literature. | journal=JAMA Dermatol | year= 2013 | volume= 149 | issue= 10 | pages= 1199-202 | pmid=23925660 | doi=10.1001/jamadermatol.2013.4885 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23925660 }} </ref> | ||
* | *Pruritus is the predominant symptom, burning with urination and dyspareunia can also be seen | ||
*On examination characteristically the lesions follow a figure of eight pattern affecting the areas around the vagina and anus | |||
*Signs of active disease include white atrophic plaques with cigarette-paper wrinkling, petechiae, fissures and erosions can be demonstrated | |||
*Examination findings of chronic disease include clitoral hood phimosis and labia minora resorption | |||
*Diagnosis confirmed with skin punch biopsy | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lichen Planus]]''' | | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lichen Planus]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
* | *Affects pre-menopausal and post menopausal women<ref name="pmid20868406">{{cite journal| author=McPherson T, Cooper S| title=Vulval lichen sclerosus and lichen planus. | journal=Dermatol Ther | year= 2010 | volume= 23 | issue= 5 | pages= 523-32 | pmid=20868406 | doi=10.1111/j.1529-8019.2010.01355.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20868406 }} </ref> | ||
*T-cell mediated inflammatory disease affecting mucosal membranes. | |||
*In erosive form patients present with vulvar pain, dyspareunia and dysuria. | |||
*Non-erosive form presents with pruritus | |||
*On examination appears lesions appear as red plaques or erosions, with overlying white violaceous or reticular plaques( Wickham Striae) | |||
*Diagnosis confirmed by shave or punch biopsy | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lichen simplex chronicus]]''' | | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lichen simplex chronicus]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*On examination leasion appear as thick, erythematous lichenified skin (epidermal thickening and accentuation of skin markings) | |||
*Due to long-term rubbing or scratching secondary to conditions such as recurrent yeast infections, contact dermatitis, psychiatric illness<ref name="pmid22594865">{{cite journal| author=Thorstensen KA, Birenbaum DL| title=Recognition and management of vulvar dermatologic conditions: lichen sclerosus, lichen planus, and lichen simplex chronicus. | journal=J Midwifery Womens Health | year= 2012 | volume= 57 | issue= 3 | pages= 260-75 | pmid=22594865 | doi=10.1111/j.1542-2011.2012.00175.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22594865 }} </ref> | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Contact dermatitis]]''' | | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Contact dermatitis]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*It could be allergic or irritant contact dermatitis | |||
*Presents with redness, swelling, and pruritus<ref name="pmid25608257">{{cite journal| author=Harper J, Zirwas M| title=Allergic contact dermatitis of the vagina and perineum: causes, incidence of, and differentiating factors. | journal=Clin Obstet Gynecol | year= 2015 | volume= 58 | issue= 1 | pages= 153-7 | pmid=25608257 | doi=10.1097/GRF.0000000000000094 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25608257 }} </ref> | |||
*Ocassionally blistering and painful bright red swelling can be seen | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Vulvar intraepithelial neoplasm]]''' | | style="padding: 5px 5px; background: #DCDCDC;" |'''[[Vulvar intraepithelial neoplasm]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Red, white, or dark raised or eroded lesions, | *Bimodal peak is observed - between 40-44years and above 55years<ref name="pmid25987900">{{cite journal| author=Preti M, Igidbashian S, Costa S, Cristoforoni P, Mariani L, Origoni M et al.| title=VIN usual type-from the past to the future. | journal=Ecancermedicalscience | year= 2015 | volume= 9 | issue= | pages= 531 | pmid=25987900 | doi=10.3332/ecancer.2015.531 | pmc=4431399 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25987900 }} </ref> | ||
*Red, white, or dark raised or eroded multifocal lesions <ref name="pmid26133495">{{cite journal| author=Nelson EL, Bogliatto F, Stockdale CK| title=Vulvar Intraepithelial Neoplasia (VIN) and Condylomata. | journal=Clin Obstet Gynecol | year= 2015 | volume= 58 | issue= 3 | pages= 512-25 | pmid=26133495 | doi=10.1097/GRF.0000000000000132 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26133495 }} </ref><ref name="pmid24399036">{{cite journal| author=Reyes MC, Cooper K| title=An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis. | journal=J Clin Pathol | year= 2014 | volume= 67 | issue= 4 | pages= 290-4 | pmid=24399036 | doi=10.1136/jclinpath-2013-202117 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24399036 }} </ref> | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vulvar cancer|Vulvar Cancer]]''' | | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vulvar cancer|Vulvar Cancer]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Presents as a solitary ulcer with raised or indurated edge | |||
*Histologically it can be a melanoma, squamous cell carcinoma, basal cell carcinoma or neuroendocrine cancer<ref name="pmid25930015">{{cite journal| author=Chokoeva AA, Tchernev G, Castelli E, Orlando E, Verma SB, Grebe M et al.| title=Vulvar cancer: a review for dermatologists. | journal=Wien Med Wochenschr | year= 2015 | volume= 165 | issue= 7-8 | pages= 164-77 | pmid=25930015 | doi=10.1007/s10354-015-0354-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25930015 }} </ref> | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Extramammary Paget's disease|Extramammary Paget disease]]''' | | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Extramammary Paget's disease|Extramammary Paget disease]]''' | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Seen in postmenopausal women | |||
*On examination it appears as a erythematous plaque with typical white scaling known as “cake-icing scaling”<ref name="van der LindenMeeuwis2016">{{cite journal|last1=van der Linden|first1=M.|last2=Meeuwis|first2=K.A.P.|last3=Bulten|first3=J.|last4=Bosse|first4=T.|last5=van Poelgeest|first5=M.I.E.|last6=de Hullu|first6=J.A.|title=Paget disease of the vulva|journal=Critical Reviews in Oncology/Hematology|volume=101|year=2016|pages=60–74|issn=10408428|doi=10.1016/j.critrevonc.2016.03.008}}</ref> | |||
*Biopsy is characterized by the presence of intraepithelial mucin-producing neoplastic cells known as Paget cells<ref name="pmid25830993">{{cite journal| author=Lopes Filho LL, Lopes IM, Lopes LR, Enokihara MM, Michalany AO, Matsunaga N| title=Mammary and extramammary Paget's disease. | journal=An Bras Dermatol | year= 2015 | volume= 90 | issue= 2 | pages= 225-31 | pmid=25830993 | doi=10.1590/abd1806-4841.20153189 | pmc=4371672 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25830993 }} </ref> | |||
|} | |} | ||
Revision as of 20:31, 10 January 2017
For patient information, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]
Synonyms and keywords: Atrophic vulvovaginitis; vaginal atrophy; urogenital atrophy; genitourinary syndrome of menopause
Overview
Historical Perspective
Classification
Pathophysiology
Pathogenesis
The pathogenesis of atrophic vaginitis is due to decreased estrogen levels. Estrogen is a vasoactive hormone, which increases blood flow and maintain vaginal lubrication through fluid transudation from blood vessels.[1] The following are the manifestations of decreased estrogen levels:[1][2][3]
- A hypoestrogenic state, such as that seen in menopause, causes the vaginal epithelium to lose its rugae, as well as become thin and pale or erythematous with fine petechial hemorrhages.
- Decreased glycogen content within the epithelium due to decreased thickness leads to less glycogen content available for the lactobacilli to utilize and turn it into lactic acid. As a result, the vaginal pH rises with a resultant overgrowth of other bacteria, such as group B streptococci, Staphylococci and diptheroids. As a result, vaginal infections, UTI and inflammation become more common in the setting of atrophic vaginitis.
Genetics
There are no genetic factors associated with atrophic vaginitis.
Gross Pathology
Gross pathology findings in atrophic vaginitis include:[4]
- Vaginal dryness
- Loss of vaginal rugae
- Changes in vaginal mucosa: pallor and friability or redness and petechiae of the mucosa
Microscopic Pathology
Associated Conditions
Causes
Atrophic vaginitis is caused by any condition that may lead to decreased circulating estrogen levels. A hypoestrogenic state may be due to ovarian failure or other causes:[1]
- Ovarian failure: this category includes menopause, premature ovarian failure, bilateral oophorectomy, chemotherapy and radiation
- Other causes: elevated prolactin levels, due to lactation or pituitary adenoma, or medications that have an anti-estrogenic effect
Epidemiology and Demographics
- Atrophic vaginitis is often an underdiagnosed condition, because many women are embarrassed to discuss their symptoms. Some others think of the symptoms associated with atrophic vaginitis as a process of natural aging.[1]
- Based on self-reported symptoms of vaginal dryness, the prevalence of atrophic vaginitis ranged from 4% to 47%, depending on the stage of menopause (early or late menopause).[2]
Risk Factors
The risk factors associated with vaginal atrophy are related to decreased estrogen levels, which can be due to menopause (most common cause) or other causes that may lead to hypoestrogenism or vaginal atrophy. These include:[1][5]
- Menopause (most common cause)
- Bilateral oophorectomy
- Premature ovarian failure
- Decreased ovarian function, due to chemotherapy or radiation
- Medications with an anti-estrogenic side effect:
- Tamoxifen
- Danazol
- Medroxyprogesterone acetate
- GnRH agonsists: leuprolide, nafarelin, goserelin
- GnRH antagonists: ganirelix
- Elevated prolactin levels during lactation
- Sexual abstinence
- Vaginal nulliparity
- Smoking
- Alcohol abuse
- Lack of exercise
Screening
There are no screening recommendations for atrophic vaginitis.[6]
Differentiating atrophic vaginitis from other diseases
Atrophic vaginitis must be differentiated from other disease processes that may present with similar symptoms. These can be divided into 4 categories:[2] [1]
- Vaginal infections: Candida vulvovaginitis, bacterial vaginosis and trichomoniasis
- Vulvovaginal dermatoses: lichen sclerosus, lichen planus and lichen simplex chronicus
- Cancer and precancerous lesions: vulvar intraepithelial neoplasia, vulvar cancer and extramammary Paget disease
- Others: foreign body, sexual trauma and contact irritants
The following is a list of differential diagnosis for Atrophic Vaginits: [7][8][5][9][10][11]
Disease | Findings |
---|---|
Atrophic vaginitis |
|
Trichomoniasis |
|
Bacterial Vaginosis |
|
Candida Vulvovaginitis |
|
Lichen Sclerosus |
|
Lichen Planus |
|
Lichen simplex chronicus |
|
Contact dermatitis |
|
Vulvar intraepithelial neoplasm | |
Vulvar Cancer |
|
Extramammary Paget disease |
Natural History, Complications and Prognosis
Natural History
Complications
Complications of atrophic vaginitis include:[1][22]
- Stress urinary incontinence
- Urge incontinence
- Pelvic organ prolapse
- Recurrent urinary tract infections
- Sexual dysfunction
Prognosis
Diagnosis
History and Symptoms
Symptoms of atrophic vaginitis can be divided into three categories:[1][2][3]
- External genital symptoms:
- Vaginal dryness
- Vaginal irritation
- Vaginal itching
- Vaginal discharge
- Sexual symptoms:
- Painful sexual intercourse (dyspareunia)
- Postcoital bleeding
- Loss of bleeding
- Loss of arousal
- Pelvic pain
- Urological symptoms:
- Burning on urination (dysuria)
- Urinary frequency
- Urinary urgency
- Nocturia
- Urinary incontinence
- Recurrent urinary tract infections (UTI)
Physical Examination
Physical examination in women with atrophic vaginitis includes a general inspection of the external genitalia, as well as a speculum examination of the internal genitalia.[3][5]
- Physical examination in women with atrophic vaginitis begins with inspection of the external genitalia. Findings include decreased elasticity of the skin, sparsity of pubic hair, dryness of the labia and/or fusion of the labia minora.
- Gynecologic examination is carried using a small speculum to avoid damage to the atrophic vaginal or vulvar tissue. Vaginal epithelium may be atrophic and appear pale, smooth and shiny, or it may be inflamed, with patchy erythema, petechiae and increased friability.
- Other findings may include: pelvic organ prolapse, such as cystocele and/or rectocele, urethral polyps or eversion of the urethral mucosa.
Laboratory Findings
CT
MRI
Ultrasound
An ultrasound of the uterus may demonstrate thinning of the endometrium lining to 4-5mm.[5]
Other Diagnostic Studies
Treatment
Medical Therapy
The mainstay of treatment of atrophic vaginitis is medical therapy. It can be categorized into two groups:[2][23]
- Nonhormonal therapy: this includes vaginal moisturizers and lubricants
- Hormonal therapy: this includes vaginally administered local estrogens, which can be in the form of cream, ring or tablet
Primary Prevention
Secondary Prevention
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA (2016). "Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management". Am. J. Obstet. Gynecol. doi:10.1016/j.ajog.2016.07.045. PMID 27472999.
- ↑ 2.0 2.1 2.2 2.3 2.4 Mac Bride MB, Rhodes DJ, Shuster LT (2010). "Vulvovaginal atrophy". Mayo Clin. Proc. 85 (1): 87–94. doi:10.4065/mcp.2009.0413. PMC 2800285. PMID 20042564.
- ↑ 3.0 3.1 3.2 Pandit L, Ouslander JG (1997). "Postmenopausal vaginal atrophy and atrophic vaginitis". Am. J. Med. Sci. 314 (4): 228–31. PMID 9332260.
- ↑ Wysocki S, Kingsberg S, Krychman M (2014). "Management of Vaginal Atrophy: Implications from the REVIVE Survey". Clin Med Insights Reprod Health. 8: 23–30. doi:10.4137/CMRH.S14498. PMC 4071759. PMID 24987271.
- ↑ 5.0 5.1 5.2 5.3 Bachmann GA, Nevadunsky NS (2000). "Diagnosis and treatment of atrophic vaginitis". Am Fam Physician. 61 (10): 3090–6. PMID 10839558.
- ↑ U.S. Preventive Services Task Force https://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=atrophic+vaginitis. Accessed on Oct. 24, 2016
- ↑ Guerrero A, Venkatesan A (2015). "Inflammatory Vulvar Dermatoses". Clin Obstet Gynecol. 58 (3): 464–75. doi:10.1097/GRF.0000000000000125. PMID 26125955.
- ↑ Centers for Disease Control and Prevention. 2015 Sexually Transmitted Diseases Treatment Guidelines. Bacterial Vaginosis. http://www.cdc.gov/std/tg2015/bv.htm Accessed on October 13, 2016
- ↑ Krieger JN, Tam MR, Stevens CE, Nielsen IO, Hale J, Kiviat NB; et al. (1988). "Diagnosis of trichomoniasis. Comparison of conventional wet-mount examination with cytologic studies, cultures, and monoclonal antibody staining of direct specimens". JAMA. 259 (8): 1223–7. PMID 2448502.
- ↑ Sobel JD, Reichman O, Misra D, Yoo W (2011). "Prognosis and treatment of desquamative inflammatory vaginitis". Obstet Gynecol. 117 (4): 850–5. doi:10.1097/AOG.0b013e3182117c9e. PMID 21422855.
- ↑ Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK (1998). "Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm". Obstet Gynecol. 92 (5): 757–65. PMID 9794664.
- ↑ Zendell K, Edwards L (2013). "Lichen sclerosus with vaginal involvement: report of 2 cases and review of the literature". JAMA Dermatol. 149 (10): 1199–202. doi:10.1001/jamadermatol.2013.4885. PMID 23925660.
- ↑ McPherson T, Cooper S (2010). "Vulval lichen sclerosus and lichen planus". Dermatol Ther. 23 (5): 523–32. doi:10.1111/j.1529-8019.2010.01355.x. PMID 20868406.
- ↑ Thorstensen KA, Birenbaum DL (2012). "Recognition and management of vulvar dermatologic conditions: lichen sclerosus, lichen planus, and lichen simplex chronicus". J Midwifery Womens Health. 57 (3): 260–75. doi:10.1111/j.1542-2011.2012.00175.x. PMID 22594865.
- ↑ Harper J, Zirwas M (2015). "Allergic contact dermatitis of the vagina and perineum: causes, incidence of, and differentiating factors". Clin Obstet Gynecol. 58 (1): 153–7. doi:10.1097/GRF.0000000000000094. PMID 25608257.
- ↑ Preti M, Igidbashian S, Costa S, Cristoforoni P, Mariani L, Origoni M; et al. (2015). "VIN usual type-from the past to the future". Ecancermedicalscience. 9: 531. doi:10.3332/ecancer.2015.531. PMC 4431399. PMID 25987900.
- ↑ Nelson EL, Bogliatto F, Stockdale CK (2015). "Vulvar Intraepithelial Neoplasia (VIN) and Condylomata". Clin Obstet Gynecol. 58 (3): 512–25. doi:10.1097/GRF.0000000000000132. PMID 26133495.
- ↑ Reyes MC, Cooper K (2014). "An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis". J Clin Pathol. 67 (4): 290–4. doi:10.1136/jclinpath-2013-202117. PMID 24399036.
- ↑ Chokoeva AA, Tchernev G, Castelli E, Orlando E, Verma SB, Grebe M; et al. (2015). "Vulvar cancer: a review for dermatologists". Wien Med Wochenschr. 165 (7–8): 164–77. doi:10.1007/s10354-015-0354-9. PMID 25930015.
- ↑ van der Linden, M.; Meeuwis, K.A.P.; Bulten, J.; Bosse, T.; van Poelgeest, M.I.E.; de Hullu, J.A. (2016). "Paget disease of the vulva". Critical Reviews in Oncology/Hematology. 101: 60–74. doi:10.1016/j.critrevonc.2016.03.008. ISSN 1040-8428.
- ↑ Lopes Filho LL, Lopes IM, Lopes LR, Enokihara MM, Michalany AO, Matsunaga N (2015). "Mammary and extramammary Paget's disease". An Bras Dermatol. 90 (2): 225–31. doi:10.1590/abd1806-4841.20153189. PMC 4371672. PMID 25830993.
- ↑ Woods NF, Mitchell ES (2005). "Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women's lives". Am. J. Med. 118 Suppl 12B: 14–24. doi:10.1016/j.amjmed.2005.09.031. PMID 16414323.
- ↑ Holmgren PA, Lindskog M, von Schoultz B (1989). "Vaginal rings for continuous low-dose release of oestradiol in the treatment of urogenital atrophy". Maturitas. 11 (1): 55–63. PMID 2498619.