Yolanda R. Smith

Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women

Prominent interindividual and sex-dependent differences have been described in responses to sustained pain and other stressful stimuli. Variations in μ-opioid receptor-mediated endogenous opioid neurotransmission may underlie some of these processes. We examined both baseline μ-opioid receptor levels and the activation of this neurotransmitter system during sustained pain using positron emission tomography in a sample of young healthy men and women. Women were studied twice, during low and high estrogen states. The high-estrogen state was associated with regional increases in baseline μ-opioid receptor availability in vivo and a greater activation of endogenous opioid neurotransmission during the pain stressor. The latter did not differ from that obtained in males. During the low estrogen condition, however, significant reductions in endogenous opioid tone were observed at the level of thalamus, nucleus accumbens, and amygdala, which were associated with hyperalgesic responses. Estrogen-associated variations in the activity of μ-opioid neurotransmission correlated with individual ratings of the sensory and affective perceptions of the pain and the subsequent recall of that experience. These data demonstrate a significant role of estrogen in modulating endogenous opioid neurotransmission and associated psychophysical responses to a pain stressor in humans.

Vulvar lichen sclerosus: Pathophysiology and treatment

AbstractLichen sclerosus is a chronic disorder of the skin and mucosal surfaces, and is most commonly seen on the female genital skin. It also occurs on other areas of the body. Any age group may be affected, although it is seen more often in elderly women. The exact cause of lichen sclerosus is unknown. There have been reports of family members with lichen sclerosus; thus it may have a genetic link. There is also the possibility of an autoimmune connection. Currently, ultra-potent topical corticosteroids are the medical treatment of choice. Other treatments that have been utilized for this condition include testosterone, progesterone, tacrolimus, surgery, and phototherapy. Surgery should be reserved for symptomatic patients who fail to respond to multiple medical treatments, as there is a high recurrence rate following surgery. The risk of developing squamous cell carcinoma of the vulva approaches 5% in women with vulvar lichen sclerosus, and therefore close surveillance by the healthcare provider and patient is needed. This review discusses the history, clinical features, pathophysiology, and treatment of lichen sclerosus of the vulva, as well as pregnancy issues and sexual function in patients with this condition. In addition, problems specific to children with lichen sclerosus are reviewed.

Complete Androgen Insensitivity Syndrome—A Review

This review paper highlights important diagnostic and therapeutic concerns for girls with Complete Androgen Insensitivity Syndrome (CAIS). CAIS is an androgen receptor defect disorder associated with vaginal and uterine agenesis in women with a 46,XY karyotype. The major clinical issues surrounding this syndrome include timing of gonadectomy, hormone replacement, vaginal dilation, and attention to psychological issues.

Processed total motile sperm count correlates with pregnancy outcome after intrauterine insemination

OBJECTIVES To determine the impact of processed total motile sperm (PTMS) count on pregnancy after partner intrauterine insemination (IUI). IUI is generally attempted before proceeding to more expensive and invasive assisted-reproductive techniques such as intracytoplasmic sperm injection. Several semen parameters have been shown to correlate with IUI outcome and may be useful when counseling couples. METHODS Four hundred thirty-eight couples with diverse causes of infertility underwent 1114 cycles of husband IUI during a 39-month period. The clinical and semen parameters were recorded for each couple and each insemination. The parameters were compared between those couples who achieved a pregnancy and those who did not. RESULTS The total number of pregnancies was 120, resulting in a pregnancy rate per cycle of 10.8% and a couple pregnancy rate of 27.4%. On multivariable logistic regression analysis, the PTMS count was independently associated with fertility after IUI (P = 0.0014). Moreover, the pregnancy rate was significantly lower for couples with less than 10 million PTMS (P <0.05). CONCLUSIONS The results of this study have demonstrated that the PTMS count independently predicts success with IUI. Cycles with less than 10 million total motile sperm are significantly less likely to result in a pregnancy. If cause-specific therapy has failed, alternatives to IUI should be considered for couples when the PTMS count is less than 10 million.

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.

Müllerian Duct Anomalies: Comparison of MRI Diagnosis and Clinical Diagnosis

OBJECTIVE The objective of our study was to assess agreement between MRI and clinical diagnosis of müllerian duct anomalies and identify causes of discrepancy. MATERIALS AND METHODS Images of 103 patients who underwent MRI for suspected müllerian duct anomaly were reviewed. Imaging included axial T1-weighted spin-echo (SE) (TR/TE, 500/10) and sagittal, long-uterine-axis, and short-uterine-axis T2-weighted fast SE (5,000/80) sequences. Agreement between original MRI diagnosis and final clinical diagnosis was assessed using the kappa statistic. Two radiologists retrospectively reviewed all cases with inconsistent MRI and clinical diagnoses to identify causes of discrepancy. RESULTS There was excellent agreement (kappa = 0.8) between MRI and clinical diagnoses of müllerian duct anomalies. For evaluation of the uterus, there was agreement in 83 of 103 patients, disagreement in 15 of 103, and agreement could not be determined in five of 103 because of uncertain MRI diagnoses. The main causes of disagreement were MRI diagnosis of septate uteri with two cervices clinically diagnosed as didelphic, partial septate uteri clinically diagnosed as arcuate, and complex anomalies with features of more than one class. The main difficulties for MRI were the detection of small uteri or remnants, characterization of cervical dysgenesis and rare anomalies, overestimation of cervical mucosal folds, characterization of anomalies in the presence of fibroids, and delineation of vaginal abnormalities. CONCLUSION Despite excellent agreement between MRI and clinical diagnoses of müllerian duct anomalies, there are discrepancies and pitfalls resulting mostly from the absence of a precise and integrated classification scheme, unfamiliarity with rare and complex entities, and suboptimal depiction of some structures on MRI.

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.

Premenarchal vaginal discharge: Findings of procedures to rule out foreign bodies

STUDY OBJECTIVE Vaginal discharge in children is a common gynecologic complaint and may be resistant to symptomatic and/or antibiotic treatment. In recurrent or unresponsive patients, an evaluation to rule out a foreign body is traditionally recommended. The objective of this study is to review cases of vaginal discharge referred to our institution and assess outcome and diagnosis in those who required irrigation or vaginoscopy to rule out a foreign body.A retrospective chart review was performed on all premenarchal girls identified through the University of Michigan Pediatric and Adolescent Gynecology Clinic database who were seen for evaluation of vaginal discharge between June 1996 and December 2001. The records were reviewed for age, length of time of discharge, aspects of discharge, procedures done to rule out foreign bodies, and findings of such procedures. SETTING The study was performed in a tertiary care university hospital. PARTICIPANTS Forty-one premenarchal girls were evaluated for vaginal discharge. The average age was 6.0 yr (range 3 months-11 yr). RESULTS The average duration of vaginal discharge prior to presentation was 13.7 months (range 1-42 months). Of the 41 girls, 18 girls underwent 1 procedure each, 2 girls underwent 2 procedures each, and 1 girl underwent 5 procedures. Ten vaginal irrigations in clinic were performed in 7 girls, 3 by the referring physician and 7 by us. These irrigations removed a foreign body (tissue paper) in 4 of 10 (40%) cases, 3 at our institution and 1 at an outside institution. In the three irrigation cases with foreign bodies performed at our institution, the foreign body was visible on genital examination prior to the irrigation. Seventeen vaginoscopies under anesthesia were performed in 16 girls, 5 by the referring physician and 12 by us. In the girls who underwent a vaginoscopy under anesthesia a foreign body was found in 3 of 17 (17.6%). The other findings of the vaginoscopies included: biopsy-proven severe dermatitis with no infection in 1 patient, lymphatic duct chylous drainage in 1 patient, nonspecific vulvovaginitis in 11 patients, and normal exam with eventual diagnosis of malingering in 1 patient. In all cases where a foreign body was identified, the patient presented with bloody or brown discharge. CONCLUSIONS Foreign bodies as a cause of persistent vaginal discharge in a tertiary care referral clinic were identified in 4 of 41 girls (9.8%) and 7 of 27 procedures (25.9%). One child had recurrent foreign bodies removed during 4 of 5 procedures for discharge. In children with persistent vaginal discharge, vaginal irrigation was feasible in older children (average age 7.7 yr). However, no foreign bodies were removed by irrigation that had not already been visually identified prior to the procedure. Exam under anesthesia and vaginoscopy allowed the identification of foreign bodies, and it facilitated the diagnosis of other unusual conditions.

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.