Gita P. Gidwani

Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina.

The relationship between cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations and congenital absence of the uterus and vagina (CAUV) was examined. CFTR mutations have previously been associated with congenital bilateral absence of the vas deferens (CBAVD). CBAVD is caused by a disruption in the vas deferens, a Wolffian duct derivative. Because the embryologic development of the Müllerian ducts directly depends on the prior normal development of the Wolffian ducts, the same gene products may be necessary for normal embryologic development of both ductal systems. This study evaluated the role of CFTR mutations in the development of CAUV. DNA samples from 25 patients with CAUV were tested for the presence of 33 of the most common CFTR mutations. Protein‐coding DNA fragments from the CFTR gene were amplified in vitro by the polymerase chain reaction (PCR) and analyzed for mutations using allele‐specific oligonucleotide (ASO) probes. Two patients were heterozygous for CFTR mutations. One was heterozygous for the W1282X mutation and the other was heterozygous for the ΔF508 mutation. The incidence of the 33 CFTR mutations found in the patients with CAUV (8%) was twice that found in the general population (4%), but much less than the incidence of CFTR mutations in men with CBAVD (80%). This data suggests that it is unlikely for CFTR mutations to cause CAUV in females as they cause CBAVD in some males. Furthermore, the data suggest that CAUV in females may be the same disorder as CBAVD in males who do not have CFTR mutations.

Laparoscopic cauterization of endometriosis for fertility: a controlled study

Ninety infertility patients with moderate endometriosis were randomized between laparoscopic electrocautery and 6 months of danazol therapy and studied for 7 months after treatment. Twenty of the 45 patients undergoing electrocautery conceived (44%) during the follow-up interval. Forty-one of the 45 patients in the danazol group completed the course of therapy, and 16 of those conceived (39%) during the same follow-up interval. There was no statistical difference between the two groups (P less than 0.53). No patients in the electrocautery group experienced complications. This demonstrates that electrocautery is safe and effective in the treatment of moderate endometriosis.

Treatment of androgenic disorders with dexamethasone: Dose-response relationship for suppression of dehydroepiandrosterone sulfate

Glucocorticoids are effective in suppressing androgens in many women whose levels of these steroids are elevated. Their use has been controversial because of inconsistent reports about efficacy and concern about safety. We investigated the dose-response relationship for suppression of dehydroepiandrosterone sulfate (DHEAS) with the use of dexamethasone. Thirty women with an initial DHEAS value of greater than or equal to 300 micrograms/dl were studied. All had cystic or inflammatory acne, hirsutism, or androgenic alopecia. Dexamethasone was given as a single bedtime dosage of 0.125, 0.250, or 0.375 mg. Mean dosage required for suppression was 0.256 mg daily. Suppression of the DHEAS level to less than or equal to 200 micrograms/dl was achieved with 0.125 mg in 25% of women, 0.250 mg in an additional 50%, and 0.375 mg in a further 20%. Most patients were taking spironolactone when the study was performed. Effective suppression is attained with dexamethasone doses significantly lower than previously thought. Use of these doses was not associated with a significant incidence of adverse effects.

Unusual presentation of lichen sclerosuis in an adolescent

Background: The presentation of lichen sclerosus has been described in detail in the adult literature. Typically present with symptoms of itching and soreness in the vulvar area at which time a vulvar evaluation reveals a specific appearance. The presentation is believed to be similar in prepubertal children and adolescents. In this case report we encountered an unusual initial presentation of this disease.Methods: Case presentation.Results: An 18-year-old female presented for the first time to her gynecologist with complaint of difficulty with complete emptying of bladder and dribbling. She had noted the onset of these symptoms two months prior to presentation. She denied any long-term history of vulvar itching or irritation. Her menses were normal with no complaints of dysmenorrhea. Onset of menarche and pubertal development were also normal. She denied any pre-pubertal history of labial adhesions or lichen sclerosis. The patient was not sexually active. She was diagnosed with labial adhesions and her first course of treatment included topical estrogen therapy for 8 weeks. Her second course of therapy included topical testosterone for 6 weeks without any improvement or side effects. On evaluation at our institution the posterior aspect of the labia minora could not be seen and the area of the vaginal introitus was completely obstructed (see picture). The clitoral hood could not be retracted and the surrounding vulva appeared atrophic and white. The degree of obstruction was such that the urethra could not be seen. In the operating room the labia minora were manually separated. The patient applied clobetasol.05% ointment for the next two weeks to the vulva and then switched to a less potent steroid. Follow-up evaluation 2 and 4 weeks after the procedure did not show any adhesions. Punch biopsy was consistent with diagnosis of lichen sclerosis.Conclusion: The presentation of lichen sclerosis may be variable in adolescents; thus, a high index of suspicion must be maintained to make this diagnosis.

Outcome of surgical reconstructive procedures for the treatment of vaginal anomalies

Abstract Study Objective: To determine the outcome of corrective surgical procedures used to treat congenital vaginal anomalies. Design: A retrospective international collaborative chart study which accumulated standardized data on patients who presented to these six institutions for surgical correction of vaginal anomalies. Participants: One hundred twenty-four procedures were performed on 74 patients. Forty-seven patients had congenital adrenal hyperplasia (CAH), 22 had congenital absence of the vagina (CAV), and 5 had complex cloacal anomalies. Primary surgical procedures were as follows: 23 of the total 28 vaginoplasties, 44 of the 76 perineoplasty procedures, and all of the 7 pull-through procedures. Main Outcome Measures: Success was based on the presence of a functioning vagina, conditional success on the presence of an acceptable vagina for stage of development, and failure on the need for further operative procedure. Results: Patients with CAH were predominantly prepubertal, noncompliant with dilators and had an overall success rate of 8.5%, conditional success rate of 22.5%, and failure rate of 66.0%. The patients with CAV had an overall success rate of any primary surgical procedure of 68.2% and all but two were postpubertal at the time of initial surgery. All five patients with complex anomalies required more than one surgery. Second procedures were more successful in all patients if performed after the age of 15 years. Conclusions: This study indicated a favorable out-come for vaginoplasty for CAV and for repeat surgical procedures if done after age 15, and that patients with CAH who have prepubertal surgery have a relatively high rate of repeat corrective surgery.

Menstrual dysfunction in hirsute women

Hirsutism in women is frequently associated with increased levels of androgens. Studies of biochemical changes, however, have yielded conflicting results. This study compares the findings in 30 hirsute women with normal menses and those of 30 hirsute women with abnormal cycles. Of the women with abnormal menstruation, 73% had oligoamenorrhea only and the others had dysfunctional uterine bleeding. The abnormally menstruating group had a similar mean age but tended to have heavier body weights than those with normal cycles. Free and total testosterone levels were significantly higher in the abnormal group (total testosterone, 54 +/- 35 ng/dl vs 35 +/- 12 ng/dl, p = 0.004; free testosterone, 7.8 +/- 4.9 pg/ml vs 4.2 +/- 1.4 pg/ml, p = 0.002). The abnormal group tended to have higher levels of androstenedione than the normal group (227 +/- 116 ng/dl vs 139 +/- 59 ng/dl) but dehydroepiandrosterone sulfate (DHEAS) levels were similar (320 +/- 142 mg/dl vs 298 +/- 169 pg/dl). Levels of thyroxin, thyrotropin, and prolactin were comparable in the two groups. Among hirsute women those with abnormal menses tended to be heavier and to have higher levels of total testosterone, free testosterone, and androstenedione. This is consistent with the clinical impression, not previously documented, that of hirsute women, those with abnormal menses have more severe endocrine abnormalities than those with normal cycles.

Bone Mineral Changes in Young Women with Hypothalamic Amenorrhea Treated with Oral Contraceptives, Medroxyprogesterone, or Placebo Over 12 Months

as predictive of reliable contraceptive use: school enrollment, not having failed a grade in school, adequate support, belief that pregnancy is likely without birth control, attendance at postpartum visit, prior abortion, and the adolescents desire to wait at least 2 years before having another child. Interventions designed to reduce the rate of repeat pregnancy during adolescent years should address emotional, financial, educational, as well as contraceptive needs of the adolescent.

Norgestimate and Ethinyl Estradiol in the Treatnent of Acne Vulgaris: A Randomized, Placebo-Controlled Trial

Two hundred and fifty women were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the effectiveness of norgestimate-ethinyl estradiol in the treatment of acne vulgaris. Subjects were 15-49 years old and had moderate acne vulgaris. Each month for 6 months, subjects received either 3 consecutive weeks of active OC treatment followed by 1 week of inactive drug, or 4 consecutive weeks of color-matched placebo tablets. Efficacy was assessed by facial acne lesion counts, the investigators global assessment, and the subjects self-assessment. Hormone levels were also measured. Despite the large placebo effect inherent in an acne trial (for example, careful skin care and frequent office visits), of the 164 subjects who completed the study without major protocol deviations, the OC group did significantly better than the placebo group, viz., inflammatory lesions were reduced. Free testosterone decreased significantly, and sex hormone-binding globulin increased significantly in the OC group, but remained unchanged in the placebo

Presentation and Management of Vaginal Septums

Background Uterovaginal anomalies have been classified and managed in a variety of ways. Although most of these anomalies are quite distinctive, some generalizations may be made. The most recent American Society of Reproductive Medicine classification of mullerian anomalies focuses mostly on disorders of lateral fusion as opposed to associated vaginal anomalies. We undertook this retrospective study to review the types of vaginal septums, their evaluation and management at a tertiary care center. Metilods All mullerian and vaginal anomalies that presented for evaluation between the years of 1993 and 1996 were reviewed. Twelve patients were identified that presented with a vaginal septum. These patients were categorized into similar groups based on the type of vaginal defect. Results Eight patients presented with longitudinal septums, six of which were obstructing (mean age=17). The latter group presented with cyclic pelvic pain, pelvic mass, notable bulge in the vagina, and both regular menstrual cycles and post menstrual bleeding. Preoperatively these patients had been evaluated with either magnetic resonance imaging or computed tomography. All six patients presented with an absent kidney. These patients then underwent diagnostic laparoscopy, resection of vaginal septum, and either hysteroscopy or hysterosalpingogram. All had associated uterine didelphus. Four patients presented with transverse septums, two of which were complete. Patients with complete obstructions presented at a mean age of 16 with primary amenorrhea, no pain, hematocolpos, and pelvic mass. These patients had resection of the vaginal septum followed by use of a dilator. Conclusions Our review suggests that the most common vaginal septum is a unilateral obstructing longitudinal type. In spite of cyclic pelvic pain these patients are diagnosed several years after menarche. Thus an absent kidney in the pediatric and adolescent population warrants a thorough workup of the mullerian derived organs and vagina. Finally the index of suspicion must be very high in diagnosing complete transverse septums since these patients may not present with pelvic pain

170 MENSTRUAL DYSFUNCTION IN ADOLESCENTS WITH INCREASED JNTIMCRANLAL PRESSURE

The menstrual cycle is controlled by the central nervous system and alterations in its function may be a reflection of neurological disease. Although longstanding increased intracranial pressure (ICP) may produce subtle but important changes such as learning disabilities, there may be few clues to identify increased ICP as the cause. We have recently seen two patients with longstanding learning disabilities in whom amenorrhea provided the impetus for CT scanning. One patient presented at 20 years of age and had an initial prolactin of 42. She had a 3rd ventricle cyst causing obstructive hydrocephalus. The second patient presented at 17 years of age with amenorrhea and severe headaches. Prolactin was 29.5 ng/ml. Hydrocephalus due to a 4th ventricle ependymoma was found on CT. Spontaneous menses occurred in the second patient after placement of a shunt. Her prolactin level gradually fell to normal but menses resumed before the prolactin fall. The first patient initially required medroxyprogesterone acetate postoperatively but resumed spontaneous menses when she was placed on spironolactone for her hirsuitism.CONCLUSIONS: 1) Amenorrhea may be an important clue to the presence of increased intracranial pressure and intracranial neoplasia, 2) Hypo-thalamic compression rather than hyperprolactinemia appears to be the mechanism of amenorrhea in our cases.