The relationship of serum androgens and ovulatory status to blood pressure in reproductive-age women.

The objective of this cross-sectional study was to determine the relationship between hyperandrogenemia and blood pressure in women with menstrual irregularities seen at an endocrinology clinic. Women with serum testosterone levels (T) > or = 30 ng/dL were more likely to have general obesity (odds ratio [OR] = 6.8, 95% confidence intervals [CI] = 2.2-27.2) and central obesity (OR = 14.5, 95% CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women (HA) had an OR of 2.4 (95% CI = 1.0-6.2) for elevated SBP and an OR of 2.7 (95% CI = 0.8-8.8) for elevated DBP, independent of age and ovulatory status. Obese HA had an OR of 4.7 (95% CI = 2.3-10.4) for elevated SBP and an OR of 2.9 (95% CI = 1.9-9.9) for elevated DBP. In conclusion, T is associated with an increased risk for obesity and central adiposity. T predicts BP elevation independent of age and ovulatory status. There was a synergistic relationship between obesity and androgens in their affect on BP.

Serum testosterone levels and reference ranges in reproductive-age women.

OBJECTIVE: To determine the levels of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) in women with no clinical signs of hyperandrogenism and no history of glucocorticoid or oral contraceptive use and to compare these levels with the reference ranges provided by commercial laboratories. METHODS: We undertook a cross-sectional retrospective study of 271 reproductive-age women encountered at an endocrinology clinic for complaints of potential thyroid problems. Serum testosterone and DHEAS levels were determined, and statistical analyses were performed. RESULTS: The serum testosterone level in women with no acne, hirsutism, or menstrual dysfunction was 14.1 +/- 0.9 ng/dL (mean +/- standard error of the mean) (95% confidence interval [CI] = 12.4 to 15.8). This group was considered our study reference population. In women with menstrual dysfunction but no acne or hirsutism, the mean testosterone level was significantly higher (17.9 +/- 1.1 ng/dL; 95% CI = 15.7 to 20.0; P<0.002); with mild hirsutism, it further increased (38.4 +/- 5.1 ng/dL; 95% CI = 27.4 to 49.4; P<0.005); and with moderate to severe hirsutism, it was still higher (49.0 +/- 2.3 ng/dL; 95% CI = 44.4 to 53.6; P<0.003). Serum DHEAS levels showed similar patterns. The upper limit (mean + 2 standard deviations) of testosterone in our study reference population was 28 ng/dL, a level that provided a sensitivity of 84% for detecting hyperandrogenemia. The detection of hyperandrogenemia is essentially impossible when the upper limit of the reference range for testosterone from commercial laboratories (95 ng/dL) is used. CONCLUSION: The testosterone levels reported herein and in the literature for hyperandrogenic women both are within the reference (normal) ranges provided by commercial laboratories. These observations demonstrate why diagnosis of hyperandrogenemia in hyperandrogenic women is difficult when commercial laboratories are used and why this condition is not detected in most affected women. Commercial laboratories should reevaluate the methods used for establishing their reference ranges for serum testosterone.

Utilization of commercial laboratory results in management of hyperandrogenism in women.

OBJECTIVE: To compare results from testosterone radioimmunoassay kits commonly used by commercial laboratories as well as their reference ranges and to analyze the scientific literature for ranges of serum testosterone levels in normal women and those with hyperandrogenism. METHODS: We reviewed quality assurance reports of various testosterone ligand challenges from four groups of laboratories and summarized testosterone data from 17 published reports about normal women and 14 studies of hyperandrogenic women. RESULTS: A significant variability was demonstrated between the radioimmunoassay kits at all concentrations (for example, a sample with a mean testosterone level of 96.1 ng/dL was reported by some laboratories as containing 71.8 ng/dL and by others as 123.4 ng/dL). All laboratories provide essentially the same "reference range" (approximately 10 to 90 ng/dL) but do not report how the range was established. The scientific literature clearly shows a significant separation in serum testosterone levels between normal (that is, not hyperandrogenic) and hyperandrogenic women. Most hyperandrogenic women had testosterone levels >50 ng/dL, whereas most normal control subjects had levels <40 ng/dL. Thus, most of these women with hyperandrogenism would have been considered to have normal testosterone levels if the reference ranges of commercial laboratories were used. CONCLUSION: These data illustrate the difficulty that physicians face when they are required to use different commercial laboratories to measure serum testosterone levels. We propose that (1) reference ranges be established on a clinically defined population for each hormone and method used, (2) laboratory reports include information about method and reference range population, and (3) physicians be allowed to choose which laboratories are used for their patients' hormone determinations, for consistency of results.

Retreatment with nafarelin for recurrent endometriosis symptoms: efficacy, safety, and bone mineral density.

OBJECTIVE: To assess the efficacy, safety, and effect on bone mineral density of a 3-month course of retreatment with intranasal nafarelin acetate for recurrent symptoms of endometriosis. DESIGN: Multicenter, open-label, nonrandomized clinical trial. SETTING: Eleven hospital-based and private practices. PATIENT(S): Thirty-six women with endometriosis symptoms recurring after 3 or 6 months of treatment with nafarelin. INTERVENTION(S): Nasal nafarelin 200 micrograms twice daily for 3 months. MAIN OUTCOME MEASURE(S): Assessments for dysmenorrhea, dyspareunia, pelvic pain, tenderness, and induration. Measurement of bone mineral density of the lumbar spine. RESULT(S): Improvements from admission to the end of retreatment were significant for dysmenorrhea, pelvic pain, tenderness, induration, and dyspareunia. Three months after retreatment ended, mean symptom scores for dysmenorrhea and pelvic tenderness, although worse than at the end of retreatment, were still significantly better than scores at admission. Mean bone mineral density 3 months after retreatment was 0.56% lower than before retreatment and 1.94% lower than before initial treatment. CONCLUSION(S): Three-month nafarelin retreatment for recurrent endometriosis symptoms was effective and safe.

Specificity of intertubular capillary changes: comparative ultrastructural studies in renal allografts and native kidneys.

The pathophysiology of chronic rejection of renal allografts is poorly understood and specific morphologic markers are being sought for its diagnosis. Ultrastructural splitting and reduplication of the basal lamina of the intertubular capillaries (ITCs) have been shown to be consistently associated with transplant glomerulopathy (TG) in renal allografts and have been used as a marker of chronic allograft rejection. Although the presence of ITC abnormalities is extremely helpful diagnostically and has been considered a surrogate for the diagnosis of TG when glomeruli are not available for examination, their specificity has not been tested. This study examined 135 biopsy specimens from renal allografts and native kidneys and categorized the ITC basal lamina alterations into 5 patterns. The results showed that although marked ITC basal lamina abnormalities are characteristically seen in association with TG, lesser degrees of these changes may also be found in native kidneys and in transplants with other types of glomerulopathies. In native kidneys, splitting and reduplication of the ITC basal lamina were observed in cases of active lupus nephritis, membranoproliferative glomerulonephritis type I, crescentic glomerulonephritis, cryoglobulinemia, and hypertension. In allografts, ITC changes were seen in postinfectious proliferative glomerulonephritis, acute cyclosporin toxicity, and hemolytic uremic syndrome, in addition to cases with TG. The histopathologic diagnosis in renal diseases relies heavily on clinical, immunofluorescence, and ultrastructural findings. Therefore, in the transplantation setting, with other less common pathological processes ruled out, the presence of abnormalities of the ITC basal lamina is highly indicative of TG. This association is particularly true for cases with severe ITC abnormalities.

The influence of semen analysis parameters on the fertility potential of infertile couples.

The objective of this study was to investigate the relationship between couples' fertility potential and several parameters of semen analysis (from a single semen sample/male partner) in a cohort of 1,055 infertile couples seen at the Texas Institute for Reproductive Medicine and Endocrinology for a total of 9,409 follow-up months. The medians of sperm concentrations (SC), total sperm counts (TSC), percent motility (MOT), motile sperm concentrations (MSC), and total motile sperm counts (TMSC) were significantly higher (P < 0.0001) in the group that achieved pregnancy. When the entire group was divided into "high" and "low" groups on the basis of the various parameters of semen analysis, the relative risk ratios for conception for the "high" groups were as follows: SC, 1.5; MOT, 8.5; TSC, 8.1; MSC, 5.8; and TMSC, 6.1. Life table analysis showed a statistically significant difference (P < 0.0001) in the initial rise and overall slope of the conception rates between the two groups for a number of the semen analysis parameters (TSC, MOT, MSC, and TMSC). This study showed that certain semen analysis parameters are positively correlated, with a high degree of statistical probability, with the time required for the occurrence of conception. The quantitative impact of the male fertility potential on conception rates was shown to correlate not solely with the SC or MOT values, but even more so with their derivatives (i.e., MSC and TMSC). Therefore, in an in vivo environment it is not only the number of sperm and their motility but also their derivatives that provide a quantitative insight into the male fertility potential. The data may provide a quantitative expression of the relative risk ratio for conception to occur and the time required until conception is achieved. Further studies will be necessary to clarify the effect of the other semen analysis parameters (i.e., morphology, velocity, linearity, and "efficient" MSC) on conception rates, cumulative conception rates, relative risk ratio for conception, and time until conception in a large population of infertile couples.

Ontogeny of testosterone production from immature mouse testes in vitro.

A dynamic superfusion system was developed to study the ontogeny of testosterone production from immature mouse testes. Testes obtained from 6-day, 12-day and 18-day old mice superfused in vitro. Their basal testosterone productivity were match to their in vivo chronic age. Superfused testes responded to pulsatile stimulation of human chorionic gonadotropin (HCG) for 42 days. Pulsatile HCG stimulation significantly enhanced testosterone production than bolus stimulation. Pulsatile FSH stimulation could significantly increase the testosterone production. Elevation of fluid pressure in culture chamber showed increase testosterone production but it was not significantly different.

Classification of Rhizomonas suberifaciens, an unnamed Rhizomonas species, and Sphingomonas spp. in rRNA superfamily IV.

Thermal melting profiles of hybrids between 3H-labeled rRNA of Rhizomonas suberifaciens, the causal agent of corky root of lettuce, and chromosomal DNAs from 27 species of gram-negative bacteria indicated that the genus Rhizomonas belongs to superfamily IV of De Ley. On the basis of the melting temperatures of DNA hybrids with rRNAs from the type strains of R. suberifaciens, Sphingomonas paucimobilis, and Sphingomonas capsulata, Rhizomonas strains constitute a separate branch in superfamily IV, which is closely related to but separate from branches containing Zymomonas mobilis, Sphingomonas spp., and S. capsulata. Sphingomonas yanoikuyae and Rhizomonas sp. strain WI4 are located toward the base of the Rhizomonas rRNA branch. DNA-DNA hybridization indicated that S. yanoikuyae is equidistant from Rhizomonas sp. strain WI4 and S. paucimobilis. Sequences of 270 bp of 16S ribosomal DNAs from eight strains of Rhizomonas spp., eight strains of Sphingomonas spp., and Agrobacterium tumefaciens indicated that S. yanoikuyae and Rhizomonas sp. strains WI4 and CA16 are genetically more closely related to R. suberifaciens than to Sphingomonas spp. Thus, S. yanoikuyae may need to be transferred to the genus Rhizomonas on the basis of the results of further study.

Prolactin response to thyrotropin-releasing hormone in normoprolactinemic patients with ovulatory dysfunction and its use for selection of candidates for bromocriptine therapy.

It has been suggested in the past that some normoprolactinemic patients with amenorrhea or infertility respond to treatment with bromocriptine. However, the beneficial effect of this therapy in normoprolactinemic women remains controversial. Some authors have suggested that the responders suffer with "reactive" hyperprolactinemia and that this may be detected with thyrotropin releasing hormone (TRH) stimulation. In this study, we performed TRH stimulation tests in 538 patients with ovulatory dysfunction. Only those patients showing a peak prolactin response after TRH which exceeded 40 ng/ml were treated with bromocriptine. A direct correlation between peak prolactin level after TRH and a favorable response to treatment was observed. Serum testosterone and DHEA-sulfate levels did not correlate with prolactin response to TRH. A majority of patients with prolactin hyperresponse to TRH did not show a hyperresponse of TSH to TRH. This study suggests that incidence of beneficial response to bromocriptine therapy in normoprolactinemic women with ovulatory dysfunction is significantly higher in subjects exhibiting excessive prolactin response to TRH stimulation.

Glucocorticoid therapy in hyperandrogenism.

Hyperandrogenism is a common disorder in the reproductive age female. It is associated with cutaneous manifestations and ovulatory dysfunction. The degree of hyperandrogenaemia is directly related to the severity of ovulatory dysfunction. The ovulatory dysfunction frequently leads to infertility. The most common form of hyperandrogenism is idiopathic glucocorticoid-suppressible hyperandrogenism (IGSH). The management of this disorder involves appropriate use of physiological doses of glucocorticoids. This treatment leads not only to normalization of serum androgen levels but also to amelioration of cutaneous symptoms and improvement in ovulatory function. In infertile women with ovulatory dysfunction secondary to IGSH, occurrence of pregnancy after treatment with glucocorticoids is directly related to the degree of the suppression of serum androgen levels. In other words, this treatment does not 'induce ovulation', but its effectiveness in improving ovulatory function is a result of a correction of the hyperandrogenic state. At physiological doses glucocorticoid therapy does not appear to be associated with significant side-effects. With appropriate management, androgen levels can be maintained within the normal range indefinitely. Furthermore, in a majority of patients, androgen levels remain within the normal range for a long time (years) after discontinuation of chronic glucocorticoid therapy.

Characterization of a 56-kb plasmid of Erwinia amylovora Ea322: its noninvolvement in pathogenicity.

A plasmid from Erwinia amylovora strain Ea322, pCPP60, was studied for its involvement in the phytopathogenicity of this strain. Eviction through incompatibility and curing with acridine orange did not affect the pathogenic capability of Ea322. The plasmid was characterized as self-transmissible with a narrow host range. Hybridization of its origin of replication with plasmids of different incompatibility groups revealed affiliation with IncF. The exact subgroup was not determined, although it does not belong to IncFI, IncFII, IncFIV, or IncFV. A sequence of 800 bp, required for conjugation in cis, was cloned in pUC9. A "miniplasmid" containing the origin of replication in a 1.2-kb sequence was constructed. Its high copy number was in contrast with the stringently controlled copy number of the native plasmid of one to three copies per chromosome equivalent.

Serum hormone changes in parturients given steroid preparations to suppress lactation.

Prior to the introduction of bromocriptine as the drug of choice for the suppression of puerperal lactation, long-acting sex steroid preparations, especially estrogen-androgen combinations, were utilized for many years to suppress postpartum lactation. In spite of the popularity of these steroids, little information is available concerning serum hormonal levels following their postpartum administration. In this study, 31 postpartum women were divided into three groups: group C, 12 women receiving no hormone therapy; group E + T, 10 women receiving an estrogen-testosterone preparation; group E, 9 women receiving an estrogen preparation. Immediately after delivery, serum estradiol, testosterone, and prolactin levels were elevated--and similar--in the three groups. Following treatment, serum estradiol levels were higher in groups E + T and E than in group C. In group E + T, serum testosterone levels increased to the high adult male range by 24 hours after injection and rose further to as high as 7,000 ng% (mean 2,000 ng%) by 72 hours. At 2 weeks, serum testosterone levels in this group of patients were still above the upper limit of the normal adult male range. After 6 weeks, the mean serum testosterone level was still five times the normal level for a nonpregnant female.

Risk factors for pregnancy loss apparent at conception in infertile couples.

Charts of 206 consecutive pregnancies occurring in couples seen because of infertility were analyzed in an attempt to identify factors, apparent at the time of conception, which may impose risks on pregnancy outcome. These factors were compared in 34 spontaneous abortions and 172 full-term pregnancies. Although the mean age was similar in both groups, women 35 years or older had a significantly higher incidence of spontaneous abortion than younger women. Menstrual history, gravidity, and parity and incidence of previous induced abortions were not different in the spontaneous abortion and term groups. Data collected from basal body temperature charts suggested a slightly higher risk for spontaneous abortion in women with previous anovulatory cycles. The mean follicular phase in the conception cycle was 16 days in both groups. However, a twofold increase in abortion rate was noticed in conceptions with follicular phases shorter than 12 days or longer than 16 days, in comparison with those with follicular phases of 13-15 days' duration. The mean daily temperature increment in the early luteal phase was the same in both groups. No relation between sperm count or motility and spontaneous abortion was observed. Different treatment modalities during the conception cycle had no effect on abortion rate, except for a trend toward lower spontaneous abortion incidence in women who received only prednisone.

Effects of cefamandole on spermatogenic development of young CD rats.

The testicular toxicity of cefamandole, a beta-lactam antibiotic with an N-methylthiotetrazole side chain, was evaluated in neonatal rats. Cefamandole caused delayed maturity of the germinal epithelium of neonatal rats when given on Postpartum Days 6 through 36. In rats given daily subcutaneous injections of 1000 mg/kg during this period, the most mature germinal cells were acrosome phase spermatids, whereas control rats had spermatids in the maturation phase. In studies of specific developmental phases, the effect of 1000 mg/kg daily cefamandole was primarily on the initial waves of spermatogonia during the period of rapid development (Postpartum Days 4 through 13). In animals treated from birth to Postpartum Day 8 and evaluated sequentially on Postpartum Days 5 through 9, there were no morphologically discernible effects on the transformation of gonocytes to immature spermatogonia, but there were slight degenerative changes in the first waves of developing spermatogonia. Cefamandole, 1000 mg/kg daily, given Postpartum Days 14 through 18 during the initial phase of spermatocyte development, also caused a slight degenerative change of the initial waves of pachytene spermatocytes. The significance of the findings in neonatal rats is unknown because differences in spermatogenic development between rat and human preclude direct extrapolation of the effects of cefamandole in neonatal rats to effects in humans.

Relationship between the results of sperm analysis and GIFT.

In vitro fertilization (IVF) and GIFT have been proposed as therapeutic approaches in infertile couples where a significant male factor is present. To date, few published data are available relating the success rate of GIFT to the severity of the male factor. In this report the results of the first 172 GIFT cases were analyzed. The overall pregnancy rate was 18.0%. The relationship between the occurrence of pregnancy and sperm count (millions/ml), total sperm count (millions/ejaculate), % motility, motile sperm count (millions/ml) and total motile sperm count (millions/ejaculate) were examined. Significant direct correlations were observed between the clinical pregnancy rate and sperm count, total sperm count, motile sperm count and total motile sperm count. Motile sperm count and total motile sperm count had the best correlations with clinical pregnancy rates, which were over 24.0% in groups with motile sperm counts exceeding 40 X 10(6) cells/ml or total motile sperm counts greater than 100 X 10(6)/ejaculate. The clinical pregnancy rates were 12.5% and 7.7%, respectively, for groups with motile sperm counts under 10 X 10(6)/ml and total motile sperm counts below 25 X 10(6)/ejaculate. No correlation was found between percent motile cells and pregnancy rate. Results of the sperm penetration assay using zona-free hamster eggs were available in a subpopulation of 27 patients. No significant correlation between this sperm penetration assay and pregnancy rate could be demonstrated. The incidence of chemical pregnancy showed a significant negative correlation with the total motile sperm count, indicating a higher incidence of early pregnancy wastage in cases of oligozoospermia.(ABSTRACT TRUNCATED AT 250 WORDS)

Annual variation in semen characteristics and plasma hormone levels in men undergoing vasectomy.

Prevasectomy levels of plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), and 20 alpha-dihydroprogesterone (20 alpha-DHP), as well as semen analyses including semen volume, sperm count, and sperm motility from 260 healthy men were evaluated for annual changes. A statistically significant (P less than or equal to 0.015) high-amplitude seasonal variation with the peak in April to May was detected in semen volume, sperm count, and sperm motility. A statistically significant (P less than or equal to 0.04) annual change of moderate T to large FSH amplitude was detected in each of the five plasma endocrine variables as well. Plasma LH, T, and E2 peaked in autumn, while FSH and 20 alpha-DHP peaked in summer. Analysis of postvasectomy LH, FSH, E2, 20 alpha-DHP, and T blood levels for the 3 years following vasectomy revealed loss of seasonal rhythmicity as a group phenomenon in LH, E2, and T. The amplitude of the seasonal variation in FSH was decreased and that in 20 alpha-DHP was unchanged compared with before-vasectomy baselines. For those annual rhythms which persisted following vasectomy, the peak time was unchanged. Compared with the prevasectomy group annual mean, that for each of the endocrine values was unchanged, except for that of LH and T, which was slightly, yet statistically significantly, elevated. The existence of prominent annual variation implicates their consideration in the design of research protocols involving investigation of reproductive phenomena in human beings.

PIP: Prevasectomy levels of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), estradiol (E2), and 20alpha-dihydroprogesterone (20alpha-DHP), as well as semen analyses including semen volume, sperm count, and sperm motility from 260 healthy men were evaluated for annual changes. A statistically significant (P or= 0.015) high amplitude seasonal variation with the peak in April-May was detected in semen volume, sperm count, and sperm motility. A statistically significant (P or= 0.04) annual change of moderate T to large FSH amplitude was detected in each of the 5 plasma endocrine variables as well. Plasma LH, T, and E2 peaked in autumn, while FSH and 20alpha-DHP peaked in summer. Analysis of postvasectomy LH, FSH, E2, 20alpha-DHP, and T blood levels for the 3 years following vasectomy revealed loss of seasonal rhythmicity as a group phenomenon in LH, E2 and T. The amplitude of the seasonal variation in FSH was decreased and that in 20alpha-DHP was unchanged compared with prevasectomy baselines. For those annual rhythms which persisted following vasectomy, the peak time was unchanged. Compared with the prevasectomy group annual mean, that for each of the endocrine values was unchanged, except for that of LH and T, which was slightly, yet statistically significantly, elevated. The existence of prominent annual variation implicates their consideration in the design of research protocols involving investigation of reproductive phenomena in humans.