Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

How does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer?

OBJECTIVE: The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life. METHODS: Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales. RESULTS: The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12-3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13-3.18), but did not differ in other quality of life measures. CONCLUSIONS: In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy.

A comparison between vaginal estrogen and vaginal hyaluronic for the treatment of dyspareunia in women using hormonal contraceptive.

OBJECTIVE: To evaluate the efficacy of topical vaginal estrogens in comparison to hyaluronic acid for the treatment of de novo dyspareunia in women using hormonal oral contraceptive (COC). STUDY DESIGN: Consecutive sexually active women using COC and complaining of de novo dyspareunia were enrolled in the study. Two attending physicians were involved in the study: the first, prescribed a 12-week vaginal estrogenic therapy with estriol 50 µg/g gel twice a week (group 1) and the second a hyaluronic acid vaginal gel therapy once a day (group 2). We evaluated dyspareunia levels using visual analogic scale (VAS) and sexual function using Female Sexual Function Index (FSFI). Vaginal atrophy was graded per the vaginal maturation index (VM). RESULTS: Overall, 31 women were enrolled. Seventeen and 14 patients were allocated in group 1 and 2, respectively. In both groups, after the topical therapy, dyspareunia, sexual function and VM were significantly improved. However, patients in group 1 experienced a significantly lower score of dyspareunia than patients in the group 2 (2 (1-7) vs. 4 (2-7); p=0.02). Additionally, women in the group 1 had higher FSFI (29.20 (24.60-34.50) vs. 28.10 (23.60-36.50); p=0.04) scores and VM (73.80 (±8.78) vs. 64.50 (±12.75); p=0.003) values in comparison to the patients in group 2. CONCLUSIONS: Our study showed that vaginal supplementation with estriol 50 µg/g gel or with hyaluronic acid could reduce the de novo dyspareunia related to COC. In this cluster of patients, both treatments improve sexuality. However, estriol 50 µg/g gel appears to be significantly more effective in comparison with hyaluronic acid.

Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients.

OBJECTIVE: Aromatase inhibitors are essential as endocrine treatment for hormone receptor-positive postmenopausal breast cancer patients. Menopausal symptoms are often aggravated during endocrine treatment. We investigated whether vaginal estriol is a safe therapeutic option to overcome the urogenital side-effects of aromatase inhibitors. Serum hormone levels were used as the surrogate parameter for safety. METHODS: Fasting serum hormone levels of ten postmenopausal breast cancer patients receiving aromatase inhibitors were prospectively measured by electro-chemiluminescence immunoassays and gas chromatography/mass spectrometry before and 2 weeks after daily application of 0.5 mg vaginal estriol (Ovestin® ovula), respectively. RESULTS: Two weeks of daily vaginal estriol treatment did not change serum estradiol or estriol levels. However, significant decreases in levels of serum follicle stimulating hormone (p = 0.01) and luteinizing hormone (p = 0.02) were observed. Five out of six breast cancer patients noticed an improvement in vaginal dryness and/or dyspareunia. CONCLUSIONS: The significant decline in gonadotropin levels, indicating systemic effects, has to be kept in mind when offering vaginal estriol to breast cancer patients receiving an aromatase inhibitor.

Clitoral and vulvar vestibular sensation in women taking 20 mcg ethinyl estradiol combined oral contraceptives: a preliminary study.

INTRODUCTION: Many women taking low-dose (20 mcg) oral contraceptive pills (OCPs) complain of decreased libido and arousal and some develop vulvar vestibular pain and dyspareunia. Free testosterone concentrations are decreased by the OCP. Genital sensation has not been objectively measured in women taking OCPs. AIM: We assessed whether the 20 mcg ethinyl estradiol combined OCP and associated decrease in free testosterone levels affected genital sensation in a pilot study of a group of asymptomatic OCP users and controls. METHODS: Clitoral thermal, vibratory, and vestibular pain thresholds, sexual functioning, and free testosterone levels were measured in 24 women taking 20 mcg ethinyl estradiol combined OCPs and 28 comparison women not using hormonal contraception. MAIN OUTCOME MEASURES: Female Sexual Functioning Index (FSFI), free testosterone, and clitoral heat, cold, and vibratory thresholds for sensation and vestibular pain thresholds. RESULTS: Free testosterone levels were lower in OCP users. There were no differences in FSFI scores, clitoral thermal or vibratory thresholds, or vestibular pain thresholds between groups. CONCLUSIONS: Low-dose (20 mcg) oral contraceptives decrease free testosterone but are not associated with alterations in clitoral or vestibular sensation. Further studies of genital sensation in women with OCP-related sexual dysfunction are warranted.

Sexual function in females after radiotherapy for rectal cancer.

BACKGROUND: Knowledge about female sexual problems after pre- or postoperative (chemo-)radiotherapy and radical resection of rectal cancer is limited. The aim of this study was to compare self-rated sexual functioning in women treated with or without radiotherapy (RT+ vs. RT-), at least two years after surgery for rectal cancer. METHODS AND MATERIALS: Female patients diagnosed from 1993 to 2003 were identified from a national database, the Norwegian Rectal Cancer Registry. Eligible patients were without recurrence or metastases at the time of the study. The Sexual function and Vaginal Changes Questionnaire (SVQ) was used to measure sexual functioning. RESULTS: Questionnaires were returned from 172 of 332 invited and eligible women (52%). The mean age was 65 years (range 42-79) and the time since surgery for rectal cancer was 4.5 years (range 2.6-12.4). Sexual interest was not significantly impaired in RT+ (n=62) compared to RT- (n=110) women. RT+ women reported more vaginal problems in terms of vaginal dryness (50% vs. 24%), dyspareunia (35% vs. 11%) and reduced vaginal dimension (35% vs. 6%) compared with RT- patients; however, they did not have significantly more worries about their sex life. CONCLUSION: An increased risk of dyspareunia and vaginal dryness was observed in women following surgery combined with (chemo-)radiotherapy compared with women treated with surgery alone. Further research is required to determine the effect of adjuvant therapy on female sexual function.

Can oral contraceptives cause vestibulodynia?

AIM: To describe the clinical course of a young woman who developed vestibulodynia with introital dyspareunia while on oral contraceptive (OCs) and to provide a possible explanation for the etiology of her symptoms as well as her recovery after treatment. METHODS: A single case is presented including subjective reporting, laboratory evaluation, and quantitative sensory testing. RESULTS: After topical hormonal therapy, the patient reported resolution of her dyspareunia and and her laboratory values normalized.

Managing the toxicities of the aromatase inhibitors.

PURPOSE OF REVIEW: The aromatase inhibitors are increasingly used as adjuvant therapy in postmenopausal women with hormone receptor positive breast cancer. With additional experience using these agents, unanticipated side effects have become apparent. Women who experience side effects from adjuvant endocrine therapy are the individuals who derive the greatest benefits. Because noncompliance is highest among those who experience side effects, it is important that these symptoms be palliated. RECENT FINDINGS: The symptomatic effects of aromatase inhibitors include: hot flashes, arthralgias, vaginal dryness and dyspareunia. Hot flashes may successfully be treated with either serotonin reuptake inhibitors or gabapentin. Counseling, vaginal moisturizers and lubricants can improve symptoms related to sexual functioning. The mechanism of arthralgias is uncertain and anti-inflammatory agents are seldom effective. Patients who experience severe musculoskeletal discomfort may necessitate switching to another endocrine agent such as tamoxifen. Physicians should be aware of 'silent' side effects. Screening for bone loss and hypercholesterolemia is critical and patients should be treated accordingly. SUMMARY: Patients and physicians should openly discuss the short and long-term side effects of the aromatase inhibitors as many of these symptoms can be managed effectively. By optimizing quality of life on adjuvant endocrine therapy, noncompliance may be minimized.

Preferences of Women Evaluating Risks of Tamoxifen (POWER) study of preferences for tamoxifen for breast cancer risk reduction.

BACKGROUND: The objective of this study was to understand the attitudes and preferences of risk-eligible women regarding use of tamoxifen for breast cancer risk reduction. METHODS: A cross-sectional, mixed-methods interview study was conducted at a university medical center and at community sites. Participants were women who had an estimated 5-year breast cancer risk > or = 1.7% and no prior breast cancer. Interviews were conducted in English or Spanish. The interview included a 15-minute, standardized educational session on the potential benefits and harms of tamoxifen followed by close-ended and open-ended questions about participants' inclinations to take tamoxifen and factors important to their decision. A demographic questionnaire, a test on knowledge of potential benefits and harms of tamoxifen, and an interview evaluation were included. RESULTS: Two hundred fifty-five women completed interviews. Their estimated mean 5-year breast cancer risk was 2.8%; and their mean self-perceived 5-year risk was 32.7%. After the educational intervention, 45 women (17.6%) were inclined to take tamoxifen. Very high risk women (> 3.5%) were no more inclined to take it than women with lower risk (1.7-3.5%). In a multivariable analysis, lower income, confidence in the effectiveness of tamoxifen, and concern about fractures were associated with being inclined to take it; concern about pulmonary embolism, dyspareunia, cataracts, and low self-perceived breast cancer risk were associated negatively with taking tamoxifen. Participants expressed concerns about adverse effects. CONCLUSIONS: Less than 20% of women were interested in tamoxifen after education about potential benefits and harms, despite a very high self-perceived breast cancer risk. Candidate chemoprevention agents must have few potential adverse effects to achieve widespread acceptance.

Acute effects of tamoxifen and third-generation aromatase inhibitors on menopausal symptoms of breast cancer patients.

Endocrine treatments of breast cancer patients antagonize estrogen and may lead to consequences of estrogen deprivation including menopausal symptoms. We analyzed the changes in frequency and severity of menopausal symptoms in patients receiving tamoxifen or aromatase inhibitors and identified factors influencing these symptoms. One hundred and eighty-one consecutive postmenopausal breast cancer patients scheduled to start endocrine treatment were included in this prospective study. A menopause symptom questionnaire covering vasomotor, atrophic, psychological, cognitive and somatic symptoms was filled in at baseline, and after 1 and 3 months of therapy. Both first-line tamoxifen and aromatase inhibitors induced an increase in the occurrence and severity of hot flashes (p<0.0001 and p=0.014, respectively). Musculoskeletal pain and dyspareunia significantly increased under first-line non-steroidal aromatase inhibitors (p=0.0039 and p=0.001, respectively), while patients under tamoxifen had significant decrease in sexual interest (p< or =0.0001). Younger age was associated with more hot flashes and vaginal dryness at baseline, and after 1 and 3 months of therapy (all p<0.02). We conclude that there are significant differences between the early effects of tamoxifen and aromatase inhibitors on menopausal symptoms of breast cancer patients. Our results underscore the need for safe and effective non-hormonal interventions to alleviate vasomotor and musculoskeletal symptoms which were the most prevalent and severe symptoms.

Chemotherapy-induced dyspareunia: a case study of vaginal mucositis and pegylated liposomal doxorubicin injection in advanced stage ovarian carcinoma.

BACKGROUND: Chemotherapy can cause vaginal irritation and mucositis, although rarely reported. CASE: A 62-year-old patient with ovarian cancer reported vaginal burning associated with dyspareunia, which emerged 3-5 days after her initial chemotherapy and persisted throughout her treatment. Her discomfort persisted until she was evaluated by our sexual health service and interventions were implemented. On examination, her vaginal vault was erythematous, with mild signs of vaginal atrophy. Her management schema consisted of the following: avoidance of intercourse 3-5 days after chemotherapy, intravaginal vitamin E suppositories three times per week, intravaginal estrogen tablets (initial course of 14 days followed by twice weekly usage), use of lubricants (Astroglide) during coitus, and counseling. Once interventions were introduced, she subsequently resumed sexual intercourse during the remainder of her chemotherapy treatments. CONCLUSION: Patients with sexual complaints during or following cancer treatment can be treated by their community gynecologists or gynecology oncologists or can be treated through a comprehensive sexual health program with restoration of sexual function.

Tamoxifen effects on subjective and psychosexual well-being, in a randomised breast cancer study comparing high-dose and standard-dose chemotherapy.

To evaluate the impact of tamoxifen on subjective and psychosexual well-being in breast cancer patients in relation to type of prior chemotherapy and menopausal status. Longitudinal interview study in breast cancer patients during and after adjuvant tamoxifen use. Menopausal status was defined by last menstrual period and serum oestradiol and FSH levels. Gynaecology outpatient clinic, Tertiary Referral Hospital, January 1995 to September 1999. Breast cancer patients <56 years of age, participating in a randomised trial comparing adjuvant high-dose (n=45) and standard-dose (n=53) chemotherapy, followed by radiotherapy and tamoxifen. Relative incidence and correlation of subjective and psychosexual symptoms during and after tamoxifen. During tamoxifen the most frequent complaints were hot flushes (85%), disturbed sleep (55%), vaginal dryness and/or dyspareunia (47%), decreased sexual desire (44%) and musculo-skeletal symptoms (43%). Disturbed sleep correlated with hot flushes (P<0.0005) and concentration problems (P<0.05). Decreased sexual interest correlated with vaginal dryness (P<0.0005) and/or dyspareunia (P<0.0005). In the high-dose group more patients became postmenopausal (95% vs 33%) and more patients reported symptoms than in the standard-dose group (P<0.05). After discontinuation of tamoxifen, symptoms decreased significantly. However, hot flushes, disturbed sleep and vaginal dryness persisted more often in patients who remained postmenopausal after high-dose chemotherapy (P<0.05). Overall, during tamoxifen patients reported many symptoms. More patients become postmenopausal after high-dose chemotherapy, and they remain often symptomatic after tamoxifen.

Comparative trial of P1496, a new non-steroidal oestrogen analogue.

The results are reported of a preliminary trial of P1496, a new non-steroidal oestrogen analogue, compared with a conjugated equine oestrogen and a placebo. The oestrogenicity of both substances was well substantiated by vaginal epithelial maturation indices. P1496 was superior to conjugated equine oestrogen in producing a significant reduction of plasma calcium levels and a possible reduction in serum cholesterol. Conjugated oestrogen caused slightly more nausea than P1496 but there were no notable side effects from either drug. P1496 is considered to be at least as effective an oestrogenic substance as conjugated oestrogen and worthy of further therapeutic evaluation.