Laser Treatment of Genito-urinary Syndrome in Women
Laser Treatment of Genito-urinary Syndrome in Women
Women with genitourinary syndrome of menopause, overactive bladder, with breast or
 endometrial cancer are randomized to either laser treatment og sham treatment for 3 months.
 The randomization is stratified for estrogen treatment. The effect is evaluated by
 questionnaire, histology and microbiology swaps
Genitourinary syndrome of menopause (GSM) is characterized by symptoms such as vaginal
 dryness, dyspareunia, irritation, urinary incontinence, overactive bladder , and urinary
 tract infections. GSM replaces the previous term vulvovaginal atrophy as agreed upon by a
 joint terminology conference sponsored by the North American Menopause Society and the
 International Society for the Study of Women's Sexual Health. GSM is a new terminology more
 accurate than the terms of VVA/atrophic vaginitis, because it describes the clinical signs
 and symptoms of the vulva, vagina and lower urinary system. In contrast, VVA/atrophic
 vaginitis describes the appearance of the vulvovaginal structures only. The GSM has a
 prevalence of more or less 50%, depending on country of origin, with a negative impact on
 sexuality, quality of life and well-being.

 The aging process is genetically determined and environmentally modulated. Estrogen
 deficiency occurring after menopause causes a series of modifications in many different areas
 of the female body, including the pelvic floor. Menopause can, therefore, lead to functional
 genital or urinary symptoms impacting women's quality of life. It is debatable to which
 extent modifications and symptoms occurring after menopause are related to estrogen
 deficiency or to the aging process per se. Vulvovaginal atrophy (VVA) involves histological,
 morphological, microbiological, and clinical changes. These include alteration in collagens,
 decreased quantity of elastic fibers, reduced vascularization, thinning and flattening of the
 vaginal epithelium, and production of glycogen, an essential factor for the growth of vaginal
 lactobacilli. As a consequence, the vaginal canal becomes shorter and narrower, and the
 vaginal epithelium becomes paler and more likely to develop petechiae. Further, a decrease in
 Lactobacillus species and a rise of vaginal pH values over 4.5 are observed, resulting in the
 loss of the local vaginal defense mechanisms against bacterial pathogens, which may
 predispose to local inflammation and/or infections.

 Women with VVA commonly complain of vaginal dryness, burning, irritation or itching, and
 dyspareunia. Local estrogens represent the first-line therapy for VVA. However, women's
 compliance with and preference for this treatment are poor; alternatives and palliative
 solutions, such as moisturizing or lubricant local creams or gels, are commonly proposed. In
 recent years, fractional CO 2 laser has become a popular, efficient, precise, and safe
 system, particularly for dermatologists and plastic surgeons. CO 2 laser has many
 applications, including treatment of skin lesions (ie, seborrheic keratosis, syringomas, and
 xanthelasmas around the eye), warts, and toenail diseases, as well as anti-aging function.

 Various therapeutic strategies, hormonal or not, oral or local, have been proposed for the
 improvement of the vaginal microecosystem of postmenopausal women (e.g. estrogens,
 probiotics, combination of vaginal estrogens with live Lactobacillus). Hormonal therapy (oral
 or local) has been associated with a healthier vaginal microecosystem by repopulating the
 Lactobacillus species to a premenopausal status and by reducing the pH of vaginal fluid.

 In women treated for estrogen dependent cancer i.e. endometrial and breast cancer women and
 practioners are reluctant to use estrogens and favor non-hormonal treatment modalities. The
 effect of these on the histological, microbiological and clinical symptoms is poorly
 understood and lack randomized trials to evaluate effect. Several proof of concept and
 feasibility studies have shown clinical effects of laser as potential treatment but little is
 known if it can stand alone or if supplementation with estrogens may benefit the clinical
 symptoms and vulvovaginal environment further. Thus, the ideal management for the achievement
 of the optimal benefit - risk balance is still under investigation. The choice of treatment
 is often guided by clinical experience and patient preference.

 In postmenopausal women, the disturbance of Lactobacillary flora was correlated with the
 presence of Gardnerella vaginalis, Trichomonas vaginalis, enterococci, group B streptococci,
 and Escherichia coli. Available data indicate that pre-existing vaginal colonization with
 pathogenic enterobacteria is essential for the appearance and recurrence of urinary tract
 infections (UTIs). Indeed, postmenopausal women are prone to UTIs with an incidence of about
 8% per year and a 4% likelihood of recurrence, while symptomatic bacteriuria was estimated in
 up to 15% of women. The general population of lactobacilli, as assessed in the routine
 practice, provides indirect information regarding the estrogenic status. To our knowledge
 there is currently no evidence regarding the potential impact that the intravaginal laser
 therapy may have on the vaginal microenvironment in women with symptoms of GSM.

 Laser treatment improves significantly the VVA symptoms, sexual function and quality of life
 of postmenopausal women, as well as the vaginal health index. Other studies found restored
 thickness of the squamous stratified epithelium of the vaginal mucosa with a significant
 storage of glycogen in the epithelial cells and remodelling the vaginal connective tissue
 with the production of new collagen and ground substance molecules.

 Breast cancer is the most common cancer in women in Denmark, annually ca. 4600 women are
 diagnosed with the disease, of whom 30% are under the age of 55. Most patients undergo breast
 conserving surgery followed by adjuvant therapy. Adjuvant therapy varies according to stage
 of disease, but radiotherapy is often added, as well as chemotherapy. If the cancer is
 hormonally responsive, long term antihormonal treatment is also given, such as the selective
 estrogen receptor modulator (SERM) tamoxifen for pre-menopausal women, that works as a
 inhibitor of estrogen in breast tissue, but as an estrogen in other tissues such as the
 endometrium. Post-menopausal women with hormone responsive breast cancer are treated with
 aromatase inhibitors for five years. Most side effects associated with tamoxifen (TAM) and
 aromatase inhibitors (AIs) are related to estrogen deprivation, and the symptoms are similar
 to those experienced during natural menopause. It has been reported that up to 50-75% of
 breast cancer survivors experience one or more genitourinary symptoms and puts the sexual
 life of women under stress. Postmenopausal women may have many common age-related symptoms
 but also have the above mentioned iatrogenic factors entering their lives to aggravate the
 symptom complex.

 The aim of the current study was to assess the effect of laser laser therapy with and without
 local estrogens. The study groups consist of 1) postmenopausal women and 2 ) women treated
 for breast cancer. The laser treatment was given randomized to these women. The effects were
 evaluated in the histopathology of the vagina, the vaginal microenvironment, and health
 related questionnaires.
Inclusion Criteria:

 -  menopause i.e. age more than 50 years and absence of menstruation for twelve months

 -  breast cancer

 -  endometrial cancer

 -  symptoms of vaginal dryness

 -  dyspareunia rated as moderate or severe most bothersome symptoms

 Exclusion Criteria:

 -  use of vaginal moisturizers, lubricants or any other local preparation within the
 thirty days prior to inclusion

 -  acute or recurrent urinary tract infections

 -  active genital infections i.e. herpes genitalis, candida

 -  previous reconstructive pelvic surgery

 -  pelvis organ prolapse stage 2

 -  any serious disease or chronic condition that could interfere with study compliance
 except from breast and endometrial cancer

 -  psychiatric disorders precluding informed consent