The association between in utero cigarette smoke exposure and age at menopause.

Menopause onset, on average, occurs earlier among women who smoke cigarettes than among women who do not smoke. Prenatal smoke exposure may also influence age at menopause through possible effects on follicle production in utero. Smoking information was obtained from the mothers of 4,025 participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, a US study begun in 1975 to examine the health effects of prenatal diethylstilbestrol exposure. Between 1994 and 2001, participants provided information on menopausal status. Cox proportional hazards modeling compared the probability of menopause among participants who were and were not prenatally exposed to maternal cigarette smoke. Participants prenatally exposed to maternal cigarette smoke were more likely than those unexposed to be postmenopause (hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). The association was present among only those participants who themselves had never smoked cigarettes (hazard ratio = 1.38, 95% confidence interval: 1.10, 1.74) and was absent among active smokers (hazard ratio = 1.03, 95% confidence interval: 0.81, 1.31). In this cohort of participants predominantly exposed to diethylstilbestrol, results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause. The possibility that active cigarette smoking modifies this effect is also suggested.

Cervical screening and general physical examination behaviors of women exposed in utero to diethylstilbestrol.

OBJECTIVE: To estimate whether women exposed in utero to diethylstilbestrol (DES) report receiving more cervical and general physical examinations compared to unexposed women. MATERIALS AND METHODS: 1994 Diethylstilbestrol Adenosis cohort data are used to assess the degree of recommended compliance of cervical screenings found in 3,140 DES-exposed and 826 unexposed women. Participants were enrolled at 4 sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data, which included reported frequency over the preceding 5 years (1990-1994) of Papanicolaou smears and general physical examinations. RESULTS: Diethylstilbestrol-exposed women exceeded the recommended frequency of Papanicolaou smear screenings [adjusted odds ratio (aOR) = 2.15, 95% CI (confidence interval) = 1.60-2.88] compared to the unexposed. This association held among those without a history of cervical intraepithelial neoplasia (aOR = 1.88, 95% CI = 1.35-2.62). Diethylstilbestrol-exposed women exceeded annual recommendations for physical examinations (aOR = 2.27, 95% CI = 1.16-4.43) among women without a history of chronic disease when compared to unexposed women. CONCLUSIONS: Most DES-exposed women are receiving cervical cancer screening at least at recommended intervals, but one third of the women are not receiving annual Papanicolaou smear examinations.

Lichen sclerosus involving the vagina.

BACKGROUND: A review of the English literature since 1940 did not reveal a reported case of lichen sclerosus involving the vaginal mucosa. Diagnosis of lichen sclerosus involving the vagina must thus be a rare occurrence. CASE: This report presents the findings on a 54-year-old white woman with a history of lichen sclerosus involving the vulva. She was found to have lichen sclerosus involving the vaginal mucosa extending to the posterior vaginal fornix. The patient was started on the use of topical clobetasol ointment 0.05% to the vulva to be used twice daily for 1 month, at bedtime for 2 months, and every other day for 3 months. At follow-up, the vulvar and vaginal lichen sclerosus was unchanged, but the patient was asymptomatic. She was using the clobetasol 1 to 2 times per week. CONCLUSION: Lichen sclerosus involving the vagina is a rare occurrence. Each case must be assessed separately and therapy initiated accordingly in each circumstance. Biopsy must be performed in all cases to identify the disease process and rule out malignancy.

Risk of benign gynecologic tumors in relation to prenatal diethylstilbestrol exposure.

OBJECTIVE: To investigate the association between prenatal diethylstilbestrol (DES) exposure and risk of benign gynecologic tumors. METHODS: We conducted a collaborative follow-up study of women with and without documented intrauterine exposure to DES. We compared the incidence of self-reported ovarian cysts, paraovarian cysts, and uterine leiomyomata confirmed by medical record in DES-exposed and unexposed women. RESULTS: A total of 85 cases of uterine leiomyomata and 168 cases of ovarian or paraovarian cysts were confirmed histologically. After adjustment for age, no association was found between prenatal DES exposure and ovarian cysts or uterine leiomyomata. Prenatal DES exposure was positively associated with paraovarian cysts. CONCLUSION: The present results do not support the hypothesis that prenatal DES exposure increases risk of uterine leiomyomata or ovarian cysts. Prenatal DES exposure was associated with an increased risk of paraovarian cysts, but detection bias cannot be ruled out as an explanation of this finding.

Findings in female offspring of women exposed in utero to diethylstilbestrol.

OBJECTIVE: To examine a group of women (third-generation daughters) whose mothers were exposed in utero to diethylstilbestrol (DES) and compare their findings on pelvic examination with those noted in their mothers. METHODS: Letters were mailed to women documented to have been exposed in utero to DES who had given birth to a female offspring, inviting them to have their daughters come in for a detailed history and pelvic examination. Records of the mothers whose daughters appeared for examination were reviewed, and findings noted at the time of their initial examination were recorded. Detailed pelvic examination of the third-generation daughters included colposcopic examination and iodine staining of the vagina and cervix and Papanicolaou smear. The findings observed in these women were compared with those noted in their mothers at the time of their mothers' first examination. RESULTS: Twenty-eight third-generation daughters were examined. Three of the daughters were delivered from one mother. Review of the mothers' records indicated that 16 (61.5%) of the mothers exposed to DES during their pregnancy demonstrated structural changes of the cervix, upper vagina, or vaginal epithelial changes consisting of adenosis, nonstaining vaginal epithelium after application of iodine solution, or white epithelium within the vagina. None of the daughters were found to have changes usually associated with DES exposure. CONCLUSION: The absence of abnormalities in the lower genital tract in third-generation women compared with the high frequency of these abnormalities in their mothers suggests that third-generation carryover effects of in utero DES exposure are unlikely.

Treatment of vulvovaginal lichen planus with vaginal hydrocortisone suppositories.

OBJECTIVE: To estimate the effectiveness of vaginal hydrocortisone suppositories in the treatment of vulvovaginal lichen planus. METHODS: A nonprobability sample of 60 patients diagnosed with vulvovaginal lichen planus were treated with intravaginal hydrocortisone 25-mg suppositories (1-1/2) twice a day. The dose was tapered to two times a week dosing after several months to maintain symptom-free disease. The participants' charts were reviewed and pretreatment symptoms and physical examination were compared to posttreatment symptoms and physical examination. Data were analyzed using McNemar chi(2). RESULTS: The sample population included mostly white (86.7%) patients with a mean age of 58 years. Forty-three participants had complete data with follow-up subjectively and objectively after treatment. Most symptoms (eg, vulvar burning, pruritus, dyspareunia, vaginal discharge) were improved and the improvement was found to be statistically significant. Sexual activity was unchanged in the women. Additionally, most physical findings by examination (eg, erythema, erosions, vulvar and vaginal lesions) were improved and the improvement was found to be statistically significant. Vaginal stenosis did not significantly improve. Treatment was continued in 35 patients with a mean duration of 28.1 months. There was overall improvement in 81% subjectively and in 76.8% objectively. CONCLUSION: Intravaginal hydrocortisone suppositories are an effective treatment for vulvovaginal lichen planus.

Treatment of vulvar intraepithelial neoplasia 2/3 with imiquimod.

OBJECTIVE: To retrospectively review the charts of 13 women diagnosed with vulvar intraepithelial neoplasia (VIN) 2/3 treated with imiquimod and to evaluate the efficacy of this treatment. STUDY DESIGN: Retrospective review. All 13 women were treated and evaluated by a single gynecologist. The extent of the lesions prior to treatment and the extent and degree of improvement were documented. Biopsy confirmation of disease was obtained for each individual. Response to treatment was categorized as complete regression, at least 75% regression or not improved. RESULTS: The mean duration of treatment was 3.3 months, and follow-up after completion of therapy was 5.5 months. Eight of the 13 women had complete regression of the VIN. Four patients demonstrated 75% regression of disease, and in one diabetic woman no improvement was seen. In two women demonstrating 75% lesion regression, invasive carcinoma of the vulva was found in the area of residual disease. In one instance this was determined to be superficially invasive squamous cell carcinoma (1 mm of invasion), and in the second an anal tag was found to have invasive squamous cell carcinoma. CONCLUSION: Medical management of VIN 2/3 with imiquimod is worth considering. However, careful evaluation of the patient must be carried out prior to the institution of therapy to exclude the presence of invasive squamous cell carcinoma.

Mammography screening behaviors of women exposed prenatally to diethylstilbestrol.

BACKGROUND: In utero diethylstilbestrol (DES) exposure is a risk factor for rare development of vaginal and cervical cancer and may potentially be a risk factor for breast cancer. Mammography use in this population is relatively unknown; therefore, this study aims to determine if in utero DES exposure is associated with the frequency of mammography screening examinations while considering demographic and clinical factors. METHODS: Using combined DES cohort questionnaire data, self-reported mammography screening over the past 5 years (2001-2006) was analyzed in women aged ≥45 years. Binary logistic regression assessed if DES exposure was associated with mammography use after adjustment for benign breast disease (BBD), previous cancer diagnosis, and whether insurance access influenced screening use. RESULTS: Overall, the frequency of mammography examinations was similar for both DES-exposed and unexposed women. DES-exposed (n=2986) and unexposed women (n=1397) over the age of 44 reported receiving ≥3 mammography examinations in the past 5 years (73.8% and 74.0%, respectively). After adjustment, DES exposure was not associated with ≥3 mammograms in the past 5 years compared to ≤2 examinations (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.86-1.17), p=0.99). CONCLUSIONS: In utero DES exposure was not associated with mammography use, nor was health insurance status or a BBD or cancer diagnosis. Because of the potential elevated risk for breast cancer in women exposed prenatally to DES, continued monitoring of standard mammography recommendations is recommended for this group, which is predominantly over the age of 45.

Autoimmune disease incidence among women prenatally exposed to diethylstilbestrol.

OBJECTIVE: Animal studies have suggested that prenatal diethylstilbestrol (DES) exposure may alter immune system development and function including antigen self-recognition. A cohort study was conducted to investigate whether prenatal DES exposure might influence the incidence of at least some specific autoimmune diseases in women. METHODS: A group of women who were and were not prenatally exposed to DES have been followed for more than 25 years for numerous health outcomes including autoimmune disease. To verify diagnoses, medical records or physician abstracts were requested for all women who reported a diagnosis of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), optic neuritis (ON), and idiopathic thrombocytopenic purpura (ITP). Incidence rates of these autoimmune diseases were compared between women who were and who were not prenatally DES-exposed. RESULTS: Overall, there was no increase in verified autoimmune disease among DES-exposed women relative to those who were not exposed (RR 1.2; 95% CI 0.7, 2.1). There was, however, a positive association between prenatal DES exposure and RA among women younger than 45 years (RR 4.9; 95% CI 1.1, 21.6) and an inverse association among women who were 45 years and older (RR 0.1; 95% CI 0.01, 0.7). CONCLUSION: Overall, these data provide little support for an association between prenatal DES exposure and development of autoimmune disease. The implication that such exposure may be related to RA in an unusual age-related manner is based on small numbers of cases and warrants further study.

Breast cancer screening in women exposed in utero to diethylstilbestrol.

PURPOSE: To determine if women exposed in utero to diethylstilbestrol (DES) are more likely than unexposed women to receive recommended or additional breast cancer screening examinations. METHODS: 1994 Diethylstilbestrol-Adenosis (DESAD) cohort data are used to assess the degree of recommended compliance of breast cancer screenings found in 3140 DES-exposed and 826 unexposed women. Participants were enrolled at four sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data that included reported frequency over the preceding 5 years (1990-1994) of breast-self examinations (BSEs), clinical breast examinations (CBEs), and mammograms. RESULTS: DES-exposed women exceeded annual recommendations for CBEs (aOR 2.20, 95% CI, 1.04-4.67) among women without a history of benign breast disease (BBD) compared with unexposed women. There were no other statistically significant differences between exposed and unexposed women who reported performing BSEs, CBEs (<40 years of age), and mammographies, regardless of BBD history. CONCLUSIONS: The majority of DES-exposed women receive breast cancer screenings at least at recommended intervals, but over two thirds do not perform monthly BSEs. Future efforts should be focused on further educating this and other at-risk populations through mailed reminders and during patient consultations on the benefits of screening examinations.

The vulvodynia guideline.

OBJECTIVE: To provide a review of the literature and make known expert opinion regarding the treatment of vulvodynia. MATERIALS AND METHODS: Experts reviewed the existing literature to provide new definitions for vulvar pain and to describe treatments for this condition. RESULTS: Vulvodynia has been redefined by the International Society for the Study of Vulvovaginal Disease as vulvar discomfort in the absence of gross anatomic or neurologic findings. Classification is based further on whether the pain is generalized or localized and whether it is provoked, unprovoked, or both. Treatments described include general vulvar care, topical medications, oral medications, injectables, biofeedback and physical therapy, dietary changes with supplementations, acupuncture, hypnotherapy, and surgery. No one treatment is clearly the best for an individual patient. CONCLUSIONS: Vulvodynia has many possible treatments, but very few controlled trials have been performed to verify efficacy of these treatments. Provided are guidelines based largely on expert opinion to assist the patient and practitioner in dealing with this condition.

Home study course: Fall 2003.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1 credit hour in Category I of the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

Detection of human cytomegalovirus DNA in 986 women studied for human papillomavirus-associated cervical neoplasia.

OBJECTIVE: The aim of this study was to assess the association of human cytomegalovirus (CMV) infection with cervical histologic findings and possible interaction with human papillomavirus (HPV) infection. MATERIALS AND METHODS: Nine hundred eighty-six women with a Pap test reported as high-grade intraepithelial lesion or with two smears reported as atypical squamous cell of undetermined significance or low grade squamous intraepithelial lesion referred for colposcopic examination were studied. All participants had a cervical Pap smear obtained and underwent colposcopically directed biopsy and endocervical curettage. Cytomegalovirus DNA and HPV DNA were detected by polymerase chain reaction (PCR) from a cervical swab. RESULTS: Human cytomegalovirus DNA was identified in 86 specimens (8.7%). Women 30 years and older had a significantly (p < .01) lower prevalence of CMV DNA (6.5%) than younger women (11.8%). Of the 86 CMV DNA-positive women, 7% had a normal histologic result, 58.1% had HPV changes (koilocytosis) in the biopsy, 11.6% had cervical intraepithelial neoplasia (CIN) 1 and 23.3% had CIN 2,3. The frequency diagnosis of koilocytosis (HPV changes) on biopsy was significantly higher in the CMV DNA-positive women (58.1%) than in the CMV negatives (29.6%). Koilocytosis on biopsy was found in 63.9% of CMV DNA-positive women who did not have concurrent HPV infection detected by PCR. Significant risk factors for koilocytosis on biopsy were CMV infection and smoking. For CIN 1, risk factors were CMV and high-risk human papillomavirus infection as well as early age of first pregnancy. The main risk factors for CIN 2,3 were HPV and CMV infections, history of smoking, and multiple pregnancies. CONCLUSIONS: The prevalence of CMV DNA is age dependent. The most frequent diagnosis on biopsy associated with CMV is koilocytosis (HPV changes), and 54% of these cases had dual HPV and CMV infection. The CMV infection appears to be associated with all histologic diagnoses, and the diagnosis of koilocytosis is not necessarily always associated with HPV infection.

Langerhans cell histiocytosis of the vulva: two case reports.

This report describes the histopathologic results of Langerhans cell histiocytosis of the vulva and options for treatment. We present two new cases demonstrating vulvar manifestations of disease and their course of treatment with a review of the literature. Langerhans cell histiocytosis of the female genital tract is rare. The disease cannot be diagnosed without biopsy of cutaneous lesions. Langerhans cell histiocytosis of the vulva is a rare disorder with few options for treatment.

Risk of breast cancer in women exposed to diethylstilbestrol in utero: prelimiinary results (United States).

BACKGROUND: A synthetic estrogen, diethylstilbestrol (DES), was widely prescribed to pregnant women during the 1950s and 1960s but was later discovered to be associated with an increased risk of clear-cell carcinoma of the vagina and cervix in female offspring. DES has not been linked to other cancers in female offspring, but studies of other prenatal factors such as twin gestation and pre-eclampsia have indicated that in-utero estrogen levels may influence breast cancer risk. We evaluated the relation of in-utero DES exposure to the risk of adult breast cancer. METHODS: A cohort of 4821 exposed women and 2095 unexposed women, most of whom were first identified in the mid-1970s, were followed by mailed questionnaires for an average of 19 years. Reported cancer outcomes were validated by medical record review. Breast cancer incidence in DES-exposed daughters was compared with cancer incidence in unexposed daughters with use of Poisson regression analysis, adjusting for year of birth, age at menarche, age at first birth, and number of births. FINDINGS: The rate ratio for incidence of invasive breast cancer in exposed versus unexposed women was 1.4 (95% confidence interval (CI) = 0.7-2.6). DES exposure was not associated with an increased risk of breast cancer in women under 40 years, but among women aged 40 and older the rate ratio was 2.5 (95% CI = 1.0-6.3). The rate ratio for the association of DES exposure with estrogen receptor-positive tumors was 1.9 (95% CI = 0.8-4.5). INTERPRETATION: While not statistically significant, the overall 40% excess risk, arising exclusively from the subset of estrogen receptor-positive cases, raises a concern calling for continued investigation.