-
Climacteric : the Journal of the... Aug 2023Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological... (Review)
Review
Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.
Topics: Humans; Female; Quality of Life; Estrogens; Vaginal Diseases; Dyspareunia; Hormone Replacement Therapy; Vagina; Atrophy; Menopause
PubMed: 37318030
DOI: 10.1080/13697137.2023.2218998 -
Nutrients May 2023Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as...
Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as ovarian function decreases. Hormone-replacement therapy is mainly used to treat menopause; however, its long-term use is accompanied by side effects such as breast cancer and endometriosis. To identify the effect of a complex extract of () and () on improving menopause without side effects, an ovariectomized rat model was established to analyze several menopause symptoms. Compared to single extracts, the complex extract restored vaginal epithelial cell thickness and decreased serotonin concentration by increasing the estrogen receptors ERα (ESR1) and ERβ (ESR2), depending on the ratio. Although the complex extract exerted a lower weight-loss effect than the single extracts, improved blood-lipid metabolism was observed after increasing high-density lipoprotein cholesterol levels and decreasing low-density lipoprotein cholesterol and triglyceride levels, and ovariectomy-induced osteoporosis was alleviated by suppressing osteoclast production. Thus, by increasing only ERβ expression without regulating ERα expression in the uterus, the complex extract of PS and NS may be a natural treatment for improving menopause symptoms without side effects, such as endometriosis.
Topics: Female; Humans; Rats; Animals; Estrogen Receptor beta; Estrogen Receptor alpha; Plant Extracts; Polygonatum; Endometriosis; Receptors, Estrogen; Menopause; Cholesterol; Osteoporosis; Hormones; Ovariectomy
PubMed: 37299404
DOI: 10.3390/nu15112443 -
Journal of Clinical Medicine May 2023This study evaluates the efficacy and safety of fractional CO lasers for treating genitourinary syndrome of menopause (GSM) in Korean women. The patients received three...
This study evaluates the efficacy and safety of fractional CO lasers for treating genitourinary syndrome of menopause (GSM) in Korean women. The patients received three laser applications at an interval of 4 weeks each. The severity of GSM symptoms was assessed using a visual analog scale (VAS) at baseline and at every visit. The objective scale was measured using the vaginal health index score (VHIS) and Vaginal Maturation Index (VMI) after completion of the laser procedure. During each procedure, the patients' pain in the VAS score was recorded. In the last visit, patients evaluated their satisfaction with the laser therapy using a 5-point Likert scale. Thirty women completed all the study protocols. After two sessions of laser therapy, some GSM symptoms (vaginal dryness and urgency) and VHIS improved significantly. After completion of the treatment, all GSM symptoms improved ( < 0.05), and the VHIS further increased significantly (VHIS at baseline, 8.86 ± 3.2 vs. V3, 16.83 ± 3.15, < 0.001). The average satisfaction was 4.3. This study shows that fractional CO laser treatment is effective and safe for Korean women with GSM. Further studies are needed to confirm these results and assess the long-term effects of laser therapy.
PubMed: 37297874
DOI: 10.3390/jcm12113679 -
The Journal of Sexual Medicine Aug 2023Based on previous studies of vaginal lubrication as well as our own previously reported interview study of women who self-reported methamphetamine (meth)-induced vaginal...
BACKGROUND
Based on previous studies of vaginal lubrication as well as our own previously reported interview study of women who self-reported methamphetamine (meth)-induced vaginal lubrication, in the current study we sought to determine the potential dose-response relationship leading to meth-induced vaginal lubrication. We also developed an animal model to study the reported effects and examine potential mechanisms mediating this phenomenon.
AIM
We sought to characterize the effects of meth on vaginal lubrication in an animal model with the aim of providing a potential framework for new mechanisms that incorporate novel therapeutic agents for the treatment of vaginal dryness.
METHODS
Vaginal lubrication was measured via insertion of a preweighed, cotton-tipped swab into the vaginal canal of anesthetized rats following treatment with various doses of intravenous (IV) meth, up to 0.96 mg/kg, and after additional pharmacological manipulations, including administration of a nitric oxide synthase inhibitor and an estrogen receptor antagonist. Plasma signaling molecules, including estradiol, progesterone, testosterone, nitric oxide, and vasoactive intestinal polypeptide, were measured immediately before and at 9 time points after IV meth administration. Blood was collected via a previously implanted chronic indwelling jugular catheter and analyzed by use of commercially available kits per the manufacturer's instructions.
OUTCOMES
Outcomes for this study include the measurement of vaginal lubrication in anesthetized rats following various pharmacological manipulations and plasma levels of various signaling molecules.
RESULTS
Meth dose-dependently increased vaginal lubrication in anesthetized female rats. Meth significantly increased plasma levels compared to baseline of estradiol (2 and 15 minutes after meth infusion) as well as progesterone, testosterone, and nitric oxide (10 minutes after meth infusion). Also, vasoactive intestinal polypeptide decreased significantly compared to baseline for 45 minutes following meth infusion. Our data further suggest that nitric oxide, but not estradiol, is critical in the production of vaginal secretions in response to meth.
CLINICAL IMPLICATIONS
This study has far-reaching implications for women who are suffering from vaginal dryness and for whom estrogen therapy is unsuccessful, as the investigation has demonstrated that meth presents a novel mechanism for producing vaginal lubrication that can be targeted pharmacologically.
STRENGTHS AND LIMITATIONS
This study is, to our knowledge, the first performed to measure the physiological sexual effects of meth in an animal model. Animals were anesthetized when they were administered meth. In an ideal situation, animals would be self-administering the drug to recapitulate better the contingent nature of drug taking; however, this method was not feasible for the study reported here.
CONCLUSION
Methamphetamine increases vaginal lubrication in female rats through a nitric oxide-dependent mechanism.
Topics: Rats; Female; Animals; Methamphetamine; Nitric Oxide; Vasoactive Intestinal Peptide; Progesterone; Lubrication; Self Administration
PubMed: 37291060
DOI: 10.1093/jsxmed/qdad076 -
Climacteric : the Journal of the... Oct 2023This study aimed to measure safety, systemic pharmacokinetics and preliminary efficacy of a vaginal tamoxifen capsule (DARE-VVA1) among postmenopausal women with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed to measure safety, systemic pharmacokinetics and preliminary efficacy of a vaginal tamoxifen capsule (DARE-VVA1) among postmenopausal women with moderate-to-severe vulvovaginal atrophy.
METHODS
This was a randomized, placebo-controlled, double-blind, phase 1/2 study of DARE-VVA1, in four doses (1, 5, 10 and 20 mg).
RESULTS
Seventeen women were enrolled and 14 completed the 8-week treatment. DARE-VVA1 was safe. All adverse events were of mild or moderate severity and distributed similarly among active and placebo groups. Plasma tamoxifen concentrations were highest among women using DARE-VVA1 20 mg, but the maximum mean (standard deviation) plasma tamoxifen concentrations on day 1 (2.66 ± 0.85 ng/ml) and day 56 (5.69 ± 1.87 ng/ml) were <14% of those measured after one oral tamoxifen dose. Active study product users had significant decreases from pre-treatment baseline in vaginal pH and proportion of vaginal parabasal cells ( = 0.04 for both endpoints), with women randomized to the 10 mg or 20 mg dose experiencing the largest treatment impact. The severity of vaginal dryness and dyspareunia decreased significantly from baseline with active study product use ( = 0.02 for both endpoints).
CONCLUSIONS
DARE-VVA1 is safe and results in minimal systemic exposure to tamoxifen. Preliminary efficacy data support further development of this product.
Topics: Female; Humans; Atrophy; Capsules; Double-Blind Method; Dyspareunia; Gelatin; Postmenopause; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva
PubMed: 37288962
DOI: 10.1080/13697137.2023.2211763 -
Cureus May 2023Background A typical symptom of patients with genitourinary syndrome of menopause (GSM) is dyspareunia. Dyspareunia has been thought to be caused by vaginal dryness. In...
Background A typical symptom of patients with genitourinary syndrome of menopause (GSM) is dyspareunia. Dyspareunia has been thought to be caused by vaginal dryness. In recent years, a survey of breast cancer survivors (BCS) with GSM has shown that para-hymen is the most painful. Dyspareunia and superficial vulvar pain (vulvodynia) may be closely linked. A recent study showed that vulvodynia is very common in BCS. Therefore, we believe treatment targeting the vagina and the vulva is necessary for pain in BCS with GSM. We hypothesized that treating both the vagina and the vulva would solve the problem of BCS with GSM. We compared the vaginal erbium SMOOTH mode laser (VEL) and neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser (VEL+Nd:YAG) combination treatment over time. This study explores therapeutic targets for pain in BCS with GSM. Methodology This retrospective, case-control study targeted sexually active BCS who reported GSM with vulvodynia and dyspareunia. After all women enrolled in the VEL treatment group had completed treatment, we treated women enrolled in the VEL+Nd:YAG treatment group. A total of 256 women who received either VEL+Nd:YAG or VEL were enrolled. Propensity score (PS)-matching analysis was used to compare two-year postoperative data retrospectively. The PS-matching results registered 102 patients in the VEL+Nd:YAG group and 102 patients in the VEL group. Symptoms were assessed using the visual analog scale (VAS) for vulvodynia before and after laser treatment for one, three, six, 12, and 24 months after completion. As a preliminary study, the vulvodynia swab test confirmed the causative location of dyspareunia. Moreover, the Female Sexual Function Index (FSFI) and Vaginal Health Index Score (VHIS) were assessed. FSFI and VHIS were treated as supplement research because the conditions were unmet. Results In the vulvodynia swab test, dyspareunia, and para-hymen (especially at 4 o'clock and 9 o'clock), all felt pain, and only a few felt pain in the vagina and labia. FSFI improved significantly in the VEL+Nd:YAG group and persisted for two years. VHIS improved equally in both groups and was not significantly different. After the first laser application, the VEL+Nd:YAG and the VEL groups showed sustained efficacy and safety in vulvodynia. Baseline VAS scores (8.74 ± 0.72 vs. 8.79 ± 0.74; p = 0.564) were similar in both groups. Both groups had a significant (p < 0.001) decrease in the VAS score. The VAS values in the VEL+Nd:YAG group and the VEL group decreased from the pretreatment to 3.79 ± 0.63 (p < 0.001 vs. baseline) and 5.56 ± 0.89 (p < 0.001 vs. baseline) after the third treatments, respectively. After 24 months, the VAS value in the VEL+Nd:YAG group and the VEL group was at 4.43 ± 1.38 (p < 0.001 vs. baseline) and 5.56 ± 0.89 (p < 0.001 vs. baseline), respectively. The side effects in both groups were short-term and minor. Conclusions Both VEL+NdYAG and VEL effectively and safely treat GSM dyspareunia and vulvodynia in BCS. Comparing the two groups, we confirmed that VEL+Nd:YAG treatment of the vaginal vestibule and vaginal opening reduced superficial vulvar pain more effectively, extensively, and over a longer period than VEL. The results of the vulvodynia swab test, FSFI, and VHIS suggest that the vulva and the vagina are important therapeutic targets for pain in BCS with GSM. The importance of treating the vulvar area for superficial pain and dyspareunia in GSM has been emphasized.
PubMed: 37284382
DOI: 10.7759/cureus.38604 -
Progres En Urologie : Journal de... Jul 2023Surgical introital reduction procedures are commonly performed for the treatment of vaginal laxity (VL), yet poorly studied. The aim of this study was to assess clinical...
OBJECTIVE
Surgical introital reduction procedures are commonly performed for the treatment of vaginal laxity (VL), yet poorly studied. The aim of this study was to assess clinical outcomes following surgical vaginal introital reduction for VL.
METHODS
This was an ambidirectional cohort study conducted in a single urogynecology center. All sexually active women who had vaginal introital surgical reduction for VL between March 2015 and September 2020 were included in this study. VL was defined as a genital hiatus distance ≥4cm according to the POP-Q classification, associated with symptoms of laxity. The primary endpoint was sexual health assessed by the Pelvi-Perineal Surgery Sexuality Questionnaire (PPSSQ), while the secondary endpoints included postoperative pain, perioperative complications, rate of dyspareunia, patient satisfaction and success rate based on the Patient Global Improvement Index (PGI-I) and Vaginal Laxity Questionnaire (VLQ).
RESULTS
Of the 27 patients sent the questionnaires, 23 sexually active patients returned the completed ones and were included in the study. Participants had a mean age and BMI of 41 years (range 24-74) and 21.3 (range 17.6-31.9) respectively. The most prevalent preoperative symptom was feeling of VL in 82.6% followed by bulging sensation in 47.8%. Preoperative dyspareunia was reported in 8/23 (34.8%). Surgical interventions involved perineorrhaphy with (n=14) or without (n=9) levator ani plication. The PPSSQ mean sexual health score was 86.7/100 (SD 5.8; range 16.7-93.3) and the mean discomfort and pain score was 27.5/100 (SD 26.0; range 0-80). Postoperative sexuality was reported to better, identical or worse in 16 (69.6%), 2 (8.7%) and 5 (21.7%) patients respectively. On PGI-I, patients reported feeling much better, better, slightly better and no change in 10 (43.5%), 5 (21.7%), 5 (21.7%) and 3 (13.0%) respectively. None of the women reported feeling worse. The overall post-operative complication rate was 3/23 (13.0%), including a perineal hematoma, and two cases of reoperation for narrow introitus. De novo dyspareunia was reported by 11/18 (61.1%) patients, occurring often or more in 4/18 (22.2%) patients, due to narrow introitus (n=2), enlarge introitus (n=1) and vaginal dryness (n=1).
CONCLUSION
Vaginal introital reduction surgery is a viable treatment option for symptoms of vaginal laxity after failure of conservative measures. However, patients should be made aware of the risk of de novo dyspareunia.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Aged; Dyspareunia; Cohort Studies; Vagina; Sexual Behavior; Pelvis
PubMed: 37263901
DOI: 10.1016/j.purol.2023.05.003 -
American Journal of Obstetrics and... Sep 2023Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen.
OBJECTIVE
This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse.
STUDY DESIGN
This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights).
RESULTS
Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference, -0.33 points; 95% confidence interval, -0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs +0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01).
CONCLUSION
Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prolapse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed.
Topics: Female; Humans; Aged; Postmenopause; Dyspareunia; Pelvic Floor Disorders; Vagina; Estrogens; Urinary Incontinence; Pelvic Organ Prolapse; Atrophy
PubMed: 37244454
DOI: 10.1016/j.ajog.2023.05.023 -
Biomedicines Apr 2023The postmenopausal state covers 40% of modern women's lives and 50-70% of postmenopausal women report GSM symptoms such as vaginal dryness, itching, frequent...
The postmenopausal state covers 40% of modern women's lives and 50-70% of postmenopausal women report GSM symptoms such as vaginal dryness, itching, frequent inflammations, lack of elasticity, or dyspareunia. Consequently, a safe and effective method of treatment is crucial. In a group of 125 patients, a prospective observational study was performed. The aim was to evaluate the clinical effectiveness of fractional CO laser in the treatment of GSM symptoms using a protocol of three procedures in 6-week intervals. The vaginal pH, VHIS, VMI, FSFI, and treatment satisfaction questionnaire were used. The fractional CO laser treatment was effective in improving all the objective forms of evaluation: vaginal pH (from 5.61 ± 0.50 at the baseline up to 4.69 ± 0.21 in the 6-week follow-up after the third procedure); VHIS (12.02 ± 1.89 at the baseline vs. 21.50 ± 1.76); VMI (21.5 ± 5.66 vs. 48.4 ± 4.46). Similar results were obtained for FSFI: 12.79 ± 5.351 vs. 24.39 ± 2.733, where 79.77% of patients were highly satisfied. Fractional CO laser therapy increases the quality of life by having a beneficial effect on the sexual function of women with GSM symptoms. This effect is obtained by restoring the correct structure and proportions of the cellular composition of the vaginal epithelium. This positive effect was confirmed by both objective and subjective forms of evaluating GSM symptom severity.
PubMed: 37238975
DOI: 10.3390/biomedicines11051304 -
Reproductive Sciences (Thousand Oaks,... Nov 2023The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative... (Meta-Analysis)
Meta-Analysis Review
The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness.
Topics: Female; Humans; Endometriosis; Progestins; Pelvic Pain; Hot Flashes; Nandrolone; Cysts
PubMed: 37217824
DOI: 10.1007/s43032-023-01266-0