Long-term estrogen replacement is associated with improved nonverbal memory and attentional measures in postmenopausal women.

OBJECTIVE: To determine the cognitive domains improved or preserved by long-term hormone replacement therapy (HRT). DESIGN: A comprehensive neuropsychological test battery was administered to healthy postmenopausal women who had been treated or not treated with long-term HRT without interruption since menopause. SETTING: Women were recruited by advertisement from a university town and surrounding areas. PATIENT(S): Women 60 years or older were studied who were treated (n = 16) or not treated (n = 13) with HRT. INTERVENTION(S): Neuropsychological testing included tests of memory, verbal fluency, executive functions, attention and concentration, and psychomotor function. Tests of intellectual function, depressive symptoms, and emotional functioning assessed general functions and comparability of the groups. MAIN OUTCOME MEASURE(S): Neuropsychological testing scores were compared between groups. RESULT(S): No statistically significant differences between the groups were found for general demographic, intellectual, and psychological measures. Scores from both the Weschler Memory Scale Visual Reproduction (delayed recall) and the Digit Vigilance Test (attention) showed statistically significant better performance and fewer errors in the group of women on HRT. CONCLUSION(S): Long-term postmenopausal HRT is associated with higher scores in tests of nonverbal memory and attention.

Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility.

OBJECTIVE: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART). DESIGN: Case series. SETTING: University fertility program. PATIENT(S): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility. INTERVENTION(S): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF. MAIN OUTCOME MEASURE(S): Pregnancy and pregnancy outcome. RESULT(S): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. CONCLUSION(S): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.

Neuroimaging of aging and estrogen effects on central nervous system physiology.

OBJECTIVE: To review the literature on neuroimaging studies focusing on gender differences in the aging process and on the effects of postmenopausal estrogen use on the brain. DESIGN: Pertinent studies were identified through a computer MEDLINE search. References of selected articles were hand-searched for additional citations. CONCLUSION(S): The current literature suggests that estrogen replacement may decrease brain white matter lesions, increase cerebral blood flow, alter regional brain activation patterns during cognitive processing, and have modulatory effects on various neurotransmitter systems. Overall, this points to a functional plasticity in higher order brain processing that can be altered by gonadal steroids.

Clobetasol propionate in the treatment of premenarchal vulvar lichen sclerosus.

OBJECTIVE: To assess the effectiveness of treating premenarchal vulvar lichen sclerosus with clobetasol propionate. METHODS: A retrospective chart review was performed of girls presenting to the University of Michigan Pediatric and Adolescent Gynecology Clinic from January, 1995, to July, 2000, with premenarchal lichen sclerosus. Subjects in the study were treated with topical clobetasol propionate ointment 0.05% for 2-4 weeks, and then tapered to a less potent steroid. Information was extracted concerning age at onset, symptoms, vulvar examination, previous treatments, effectiveness of clobetasol, follow-up, and complications. The parents were contacted for a follow-up telephone survey. RESULTS: Fifteen girls averaging 5.7 years at the start of symptoms met criteria. The diagnosis of lichen sclerosus was made visually in 11 and by biopsy in four. Follow-up ranged from 2 months to 6 years. Fourteen girls had good improvement within 4-7 weeks. One girl developed a yeast superinfection and one developed transient erythema. At least 1 year of follow-up by clinic visit or telephone interview was available in 11 girls. Of these 11, two girls had no further vulvar symptoms after the initial treatment, five had one or two total flares, three reported three to eight flares per year, and one girl continues to be unresponsive to therapy. CONCLUSION: Clobetasol propionate was an effective treatment of premenarchal vulvar lichen sclerosus in this small group; however, recurrences were common and required additional steroid treatment. Furthermore, complications of treatment were infrequent, minor, and easily treatable.

Comparison of microscopic examination and human papillomavirus DNA subtyping in vulvar lesions of premenarchal girls.

STUDY OBJECTIVE: The purpose of this study is to compare the microscopic examination and human papillomavirus (HPV) DNA subtyping of vulvar specimens from premenarchal girls clinically diagnosed with condyloma to determine whether DNA subtyping aids in the diagnostic process. DESIGN: A retrospective chart review was performed on all premenarchal girls who underwent surgical treatment of clinically diagnosed condyloma between 1993 and 1999 at the University of Michigan Medical Center by the Pediatric and Adolescent Gynecology Service. Tissue was sent for pathologic evaluation and in 10 patients the specimens also underwent DNA subtyping. One patient had prior DNA subtyping. All the other lesions were surgically ablated. The microscopic slides were reviewed by a single pathologist blinded to the study. SETTING: The study was performed in a tertiary care university hospital. PARTICIPANTS: The study group included 11 premenarchal girls with an average age of 2.3 yr. MAIN OUTCOME MEASURES: The charts were reviewed for previous HPV treatment, maternal history of HPV, history of sexual abuse, microscopic diagnosis, and HPV DNA subtyping. RESULTS: Four patients had prior surgical treatment and two patients had undergone prior medical treatment. The microscopic diagnosis was condyloma in 8 patients, chronic dermatitis in 2 patients, and 1 patient had VIN 2-3. All 11 specimens tested positive for HPV DNA, 10 specimens contained at least one of the low-risk subtypes (6, 11, 42, 43, 44), and 1 tested positive for low-risk as well as intermediate/high-risk HPV subtypes (16, 18, 31, 33, 35, 45, 51, 52, 56). CONCLUSIONS: Although all the patients with a clinical diagnosis of condyloma tested positive for HPV DNA, only 9 of 11 were definitely diagnosed with HPV-related pathology by microscopic examination. Therefore, in premenarchal patients with verrucous lesions in the anogenital area, microscopic evaluation alone may be inadequate as a confirmatory test when a positive clinical diagnosis has been made, and HPV DNA subtyping should be considered to avoid confusion with the diagnosis.

Regional mu opioid receptor regulation of sensory and affective dimensions of pain.

The endogenous opioid system is involved in stress responses, in the regulation of the experience of pain, and in the action of analgesic opiate drugs. We examined the function of the opioid system and mu-opioid receptors in the brains of healthy human subjects undergoing sustained pain. Sustained pain induced the regional release of endogenous opioids interacting with mu-opioid receptors in a number of cortical and subcortical brain regions. The activation of the mu-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience, with distinct neuroanatomical involvements. These data demonstrate the central role of the mu-opioid receptors and their endogenous ligands in the regulation of sensory and affective components of the pain experience.

Effects of long-term hormone therapy on cholinergic synaptic concentrations in healthy postmenopausal women.

Experimental evidence suggests that gonadal steroids regulate brain neurochemical systems associated with cognitive function, such as the cholinergic system. This study examines the effect of long-term postmenopausal hormone therapy on the brain concentrations of cholinergic synaptic terminals in women using single photon emission computed tomography and the radiotracer [(123)I]iodobenzovesamicol ([(123)I]IBVM). [(123)I]IBVM labels the vesicular acetylcholine transporter (VAChT) located in the presynaptic terminals of these neurons. Sixteen healthy women treated with hormone therapy since the menopause and 12 women not treated with hormones were studied. There were no significant differences in regional IBVM binding indexes between the 2 groups. The length of hormone replacement therapy correlated positively with VAChT binding indexes in multiple cortical areas (P < 0.05): frontal cortex (Spearman rank correlation: rho = 0.79), parietal cortex (rho = 0.62), temporal cortex (rho = 0.80), anterior cingulate (rho = 0.71), and posterior cingulate (rho = 0.63), but not in the basal ganglia (rho = 0.35; P = 0.2). An earlier onset of menopause in hormone-treated women was associated with higher VAChT indexes in the anterior cingulate (rho = -0.56; P = 0.02) and posterior cingulate (rho = -0.63; P = 0.01). The opposite was found in the posterior cingulate of women not treated with hormones (rho = 0.58; P = 0.04). Women treated with estrogen alone also showed higher VAChT indexes than women treated with estrogen and progestin in the posterior cingulate cortex (by Mann-Whitney U test: z = 2.42; P = 0.015). Although an overall effect of postmenopausal hormone therapy was not found, associations between an index of cortical cholinergic terminal concentrations and the length of hormonal replacement suggest that hormone therapy may influence the survival or plasticity of these cells in postmenopausal women. The data also suggest possible differential effects of estrogen and estrogen with progestin treatments in brain areas critical for cognitive processing.

Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma.

Actin-scavenging proteins, e.g., plasma gelsolin, counteract the pathophysiological consequences of actin leaked into the circulation from dying cells, but the capacity of this defense system can be overwhelmed by massive tissue injury. We examined the prognostic implications of plasma gelsolin levels obtained near the time of admission to our level I Trauma Unit on the subsequent clinical course in a group of patients with severe traumatic injuries. Blood samples were obtained from 13 patients shortly after major trauma and 11 healthy volunteers who served as the control group. Plasma gelsolin levels were assayed by quantitative Western blotting. Duration of mechanical ventilation, stay in the Trauma Intensive Care Unit, and development of acute respiratory distress syndrome (ARDS) were measured as clinical outcomes reflecting the complexity of the hospital course. Subsequently, we evaluated an additional 52 patients after major and minor trauma to extend our earlier observations. Plasma gelsolin concentrations were significantly lower in our 13 original patients compared with healthy controls. Levels below 250 mg/L (> 2 standard deviations below the mean of the control group) were associated with prolonged mechanical ventilation and a stay in the intensive care unit >/= 13 days. Both patients whose gelsolin level was < 100 mg/L in this first series developed ARDS. Including all 65 patients, 6 of the 10 patients who developed ARDS had admission gelsolin levels less than 250 mg/L, compared with only 7 of the 55 patients without ARDS (p = 0.0028). The mean gelsolin levels were 193 and 400 mg/L in patients with and without ARDS, respectively (p < 0.0001) and 398 mg/L in survivors versus 259 mg/L for patients who expired (p < 0.0001). Ten of the 13 patients (77%) with gelsolin levels at the time of admission more than 2 SD below the control mean had "bad outcomes," defined as mechanical ventilation for >/= 13 days in the Trauma Intensive Unit, ARDS, and/or death. Plasma gelsolin levels appear to be an early prognostic marker in patients experiencing major trauma. Whether circulating gelsolin serves a biologically vital function or is simply depleted after massive trauma cannot be determined from our study. The potential therapeutic benefits of infusions of recombinant human plasma gelsolin for patients in whom multiorgan dysfunction commonly follows a serious but self-limited insult have not yet been investigated.

Vulvar disorders in adolescent patients.

This article describes the most commonly encountered vulvar disorders in adolescents and refers to some less common entities. The categories are based upon appearance of the vulvar lesions: solid, cystic, ulcerative and infectious.

Ovarian surgery in premenarchal girls.

STUDY OBJECTIVE: This study was undertaken to assess the indications, procedures, and pathology in premenarchal girls undergoing ovarian surgery. DESIGN: Retrospective chart review. SETTING: University of Michigan Medical Center 1980-1996. PARTICIPANTS: Premenarchal girls, who underwent ovarian surgery. INTERVENTIONS: None. MAIN OUTCOME MEASURES: All available charts (n = 52) had information extracted concerning age at time of surgery, presenting symptoms, preoperative and postoperative diagnosis, procedure, and pathology report. RESULTS: Of the 52 patients, 50% were less than 1 year old, 31% were between 1 and 8 years old, and 19% were between 8 and 12 years old. Presenting complaints in 31 patients included structural and or endocrinologic abnormalities, and the other 21 patients presented with abdominal or systemic complaints. The most common preoperative diagnosis was an abdominal/pelvic mass (n = 24). The postoperative diagnoses revealed 18 torsions and 16 ovarian masses without torsion, 8 chromosomal abnormalities, 5 hernias, and 5 malignancies. Procedures included 37 salpingo-oophorectomies (28 unilateral and 9 bilateral), 7 oophorectomies, and 7 cystectomies. One patient underwent a staging procedure. Pathology reports confirmed hemorrhagic infarctions (n = 19), dysgenic gonads (n = 8), simple cysts (n = 7), teratomas (n = 6), theca lutein cysts (n = 4), fibroma (n = 1), stromal tumor (n = 1), mucinous cystadenoma (n = 1), granulosa cell tumor (n = 1), uterine neuroblastoma (n = 1), mixed germ cell neoplasm (n = 1), metastatic Wilms' tumor (n = 1), and gonadoblastoma (n = 1). CONCLUSIONS: Torsion was the most common diagnosis in our study group and was usually unsuspected. Premenarchal ovarian surgery usually included removal of the entire ovary. However, because malignancies are uncommon in this population (9.6%), a cystectomy should be considered when appropriate and technically feasible.

Brain opioid receptor measurements by positron emission tomography in normal cycling women: relationship to luteinizing hormone pulsatility and gonadal steroid hormones.

The regulation of central mu-opioid receptors in women during the menstrual cycle was explored with positron emission tomography and the selective radiotracer [11C]carfentanil. Ten healthy women were studied twice, during their follicular and luteal phases. Plasma concentrations of estradiol, progesterone, testosterone, and beta-endorphin were determined immediately before scanning. LH pulsatility was measured over the 9 h preceding each of the two positron emission tomography scans. No significant differences in the binding potential of mu-opioid receptors (binding capacity/Kd) were observed between phases of the menstrual cycle. However, significant negative correlations were observed between circulating levels of estradiol during the follicular phase and mu-receptor binding measures in the amygdala and hypothalamus, two regions thought to be involved in the regulation of GnRH pulsatility. LH pulse amplitude was positively correlated with mu binding in the amygdala, whereas LH pulse number was negatively correlated with binding in this same region. No significant associations were noted between LH pulse measures and the hypothalamus for this sample. These results suggest that amygdalar mu-opioid receptors exert a modulatory effect on GnRH pulsatility, and that circulating levels of estradiol also regulate central mu-opioid function.

Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction.

OBJECTIVE: To determine whether newer monitoring techniques, including urinary detection of the LH surge and vaginal ultrasound, offer an advantage over basal body temperature (BBT) charts alone in achieving pregnancy using clomiphene citrate (CC). DESIGN: Randomized clinical trial. SETTING: Infertility patients in an academic research environment. PATIENT(S): Forty-five women undergoing ovulation induction with CC. INTERVENTION(S): The women were assigned randomly to receive either low- or high-technology ovulation monitoring for a total of 3 ovulatory cycles. Both groups were followed with BBT charts. The high-technology group also was monitored with urinary LH kits and vaginal ultrasound. MAIN OUTCOME MEASURE(S): Cycle fecundity rates for each technique were compared statistically with use of life-table analysis. RESULT(S): Forty-five patients were studied during a total of 134 cycles. The overall cycle fecundity rate was 8%, 10% (8 of 81 cycles) for the low-technology monitoring group and 6% (3 of 53 cycles) for the high-technology monitoring group. These rates were not statistically significant when evaluated by Fisher's exact test (P = .53) or when using life-table analysis and a log-rank test (P = .48). CONCLUSION(S): These data suggest that, for initial attempts at ovulation induction with CC in unselected patients, high-technology monitoring of ovulation offers no increase in fecundity over low-technology monitoring.

Menorrhagia in adolescents requiring hospitalization.

STUDY OBJECTIVE: This study was undertaken to assess the causes and treatments of menorrhagia in adolescents hospitalized for this menstrual disorder. DESIGN: A retrospective chart review was performed of all adolescents < or =20 years of age with menorrhagia admitted at the University of Michigan from 1979 to 1995. Information regarding medical history, hematologic parameters, treatment, and diagnosis was extracted from each chart. Pregnant and premenarchal patients were excluded. RESULTS: Thirty-seven adolescents with 46 admissions for menorrhagia were identified. The average age of menarche was 12.9 years and the average age at admission was 15.9 years. Nineteen adolescents had significant medical diseases. For the 46 admissions, causes of menorrhagia were anovulation (21), hematologic disease (15), chemotherapy-related (5), and infections (5). Transfusions of blood products were performed in 28 of the admissions. Treatments included oral contraceptive pills or progestins (30), intravenous conjugated estrogens (8), antibiotics (4), immune gammaglobulin (3), DDAVP (3), and prednisone (1). Twelve surgical procedures were performed, including eight dilatation and curettages (D&Cs), three laparoscopies, and one hysterectomy. CONCLUSIONS: Sixty-one percent of admissions for adolescent menorrhagia were in adolescents with significant medical problems. The patients with menorrhagia who required admission had severe anemia and were transfused in 63% of cases. The predominant causes for these admissions included anovulation in 46%, hematologic disease in 33%, chemotherapy in 11%, and infection in 11%. Hormonal regulation or suppression of menses should be considered in adolescents with significant medical disease.

Recurrent benign müllerian papilloma of the cervix.

A 4-year-old girl with a recurrent benign cervical müllerian papilloma is presented. Benign müllerian papillomas are rare cervical and vaginal lesions of childhood, with only two recurrences previously reported. This lesion was originally biopsied and later rebiopsied and completely fulgarated with electrocautery. One year later, the lesion recurred and was biopsied but not completely excised because of concern that complete excision of this benign, asymptomatic lesion would cause significant damage to her cervix. A review of the literature on this subject is presented.

Ultrasonic surgical aspiration to treat genital condyloma acuminata in children.

We report on the technique of ultrasonic surgical aspiration for the treatment of genital condyloma acuminata in three prepubertal girls. All surgical procedures were done under general anesthesia, and no patient required hospitalization. Adequate samples for pathologic evaluation were obtained. This technique resulted in minimal discomfort, rapid healing, and no scarring.

Cocaine downregulates beta-adrenergic receptors in pregnant sheep myometrium.

Cocaine abuse is associated with premature labor. Although cocaine is known to competitively inhibit beta-adrenergic receptor binding, cocaine's effect on receptor downregulation is uncertain. This study was designed to determine the in vitro effect of cocaine on downregulation of beta-adrenergic receptors in pregnant myometrium. Pregnant sheep myometrium was incubated with either cocaine, isoproterenol, or a cocaine metabolite, benzoylecgonine. Membrane fractions were assayed for beta-adrenergic receptors using (125I)-cyanopindolol and the beta 2-adrenergic antagonist ICI 118,551. We found that cocaine (10(-6) to 10(-4) mol/L), but not benzoylecgonine, downregulated both beta 1- and beta 2-adrenergic receptors, but did not further augment receptor downregulation by isoproterenol. The 46% decrease in beta-adrenergic receptors seen after exposure to cocaine was similar to the 53% decrease seen after isoproterenol. We hypothesize downregulation of beta-adrenergic receptors by cocaine may play a role in the association of cocaine abuse with premature labor.

Ambiguous genitalia in an elderly woman with a mosaic 45,X/46,X,dic(Y)(Q11.2) karyotype.

A 66-year-old woman presented with clitoromegaly since childhood, primary amenorrhea, no breast development, and a large right inguinal hernia. A mosaic karyotype was identified containing a predominant 45,X cell line and a cell line with 46 chromosomes, one X chromosome, and a small dicentric Y chromosome with a breakpoint in band qII.2. The patient underwent hysterectomy, bilateral gonadectomy, inguinal hernia repair, clitoral recession, and formation of a neointroitus. A dysgerminoma was identified in the right dysgenetic gonad. This report demonstrates the natural history of untreated mixed gonadal dysgenesis and the importance of early evaluation and treatment, as well as the molecular characterization of a dicentric Y chromosome.

Decrease in myometrial beta-adrenergic receptors with prenatal cocaine use.

OBJECTIVE: To determine if cocaine use during pregnancy is associated with a reduction in the number or affinity of beta-adrenergic receptors in human myometrium. METHODS: Myometrium was obtained at cesarean delivery of five women who reported using cocaine during pregnancy and from ten controls. Saturation binding assays were performed on the myometrial membrane fractions using [125I]-cyanopindolol to determine beta-adrenergic receptor concentration and affinity. The percentages of beta 1- and beta 2-adrenergic receptors were determined in three cocaine users and four control patients by performing competition binding assays using the beta 2 antagonist ICI 118,551. Results were compared using unpaired Student t tests. RESULTS: Women who reported using cocaine during pregnancy had a significantly lower mean (+/- standard deviation) concentration of myometrial beta-adrenergic receptors than did controls (22 +/- 8 versus 52 +/- 23 fmol/mg protein, respectively). There was no difference in the receptor affinity constants between cocaine users and controls (16 +/- 2 pmol/L for both groups). The percentages of beta 1- and beta 2-adrenergic receptors in the myometrium of the cocaine-use group and control group were similar: 86 +/- 1% beta 2 in the cocaine-use group and 83 +/- 7% beta 2 in the control group. CONCLUSION: Cocaine use during pregnancy may be associated with a down-regulation of beta-adrenergic receptors in human myometrium. This could result in a decreased capacity for uterine relaxation and, consequently, a predisposition to preterm labor.

Laparoscopic irrigation using a prewarmed pressurized system.

An automatic pressure infusion system equipped with a fluid warmer has been developed for rapid intravenous infusion of homeothermic fluids. The use of this system for irrigation during operative laparoscopy provides the surgeon with the ability to irrigate at a relatively high flow while avoiding the hypothermic effects of irrigation with cool fluids.

Kallmann's syndrome: pregnancy achieved through gamete intrafallopian transfer.

This case report describes the use of GIFT to achieve pregnancy for a man with Kallmann's syndrome who obtained only marginal sperm counts with both the pulsatile GnRH infusion pump and gonadotropin injections. Failure of this man to achieve a pregnancy with hormonal therapy alone and in combination with IUI suggests that assisted reproductive technologies should be considered in male patients with Kallmann's syndrome when suboptimal sperm concentrations are achieved despite exogenous hormonal stimulation.