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PubMed2000

The gonadotropic axis in hyperandrogenic adolescents.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder that is first clinically diagnosable approximately 3 years after menarche. Women with PCOS have exaggerated gonadotropin secretion, with an elevated LH/FSH ratio, as well as an increased frequency and amplitude of LH pulsations. Since the elevated pulse frequency is a marker of unusually rapid hypothalamic GnRH secretion, these results imply a defect at the level of the hypothalamus. Such an abnormality could theoretically be a primary defect that could cause PCOS, and if so, would be expected to be detectable at the onset of puberty. How these abnormalities of hypothalamic and pituitary function relate to other, seemingly disparate, organ defects has not yet been delineated. We studied 99 PCOS patients and 42 normal controls with 8 to 12 hours of q10 min frequent blood sampling. Women with PCOS had significantly elevated mean LH levels, LH pulse amplitude, LH pulse frequency, and LH/FSH ratios compared to normal women. However, these abnormalities were not randomly distributed. All gonadotropin secretion parameters tended to be normal in PCOS patients when measured during the luteal phase or first 7 days after an ovulatory menses. There was a strong inverse relationship of mean LH, LH/FSH ratio, and LH pulse amplitude, but not frequency, with BMI. We hypothesize that this effect of body size occurs at the pituitary level. Several investigators have performed similar investigations in adolescent girls with regular and irregular menstrual cycles. Taken together, this evidence suggests that the gonadotropin defects appear as a very early finding in the development of PCOS, but the presence of abnormalities in both gonadotropin secretion and androgen secretion does not allow one to conclude that the gonadotropin defects are causal. We conclude that gonadotropin defects, particularly excess of serum LH, is a predominant finding in hyperandrogenic women, whether they are young peripubertal adolescents, or older perimenopausal women. Whether there is a primary neuroendocrine abnormality driving excess gonadotropin secretion that causes the hyperandrogenic condition, or whether the excess gonadotropin secretion reflects abnormal feedback of another factor, still remains unknown.

Adolescent↗
PubMed1999

Pharmacokinetics of progesterone administered by the oral and parenteral routes.

Progestogens, which include the natural hormone, progesterone, and synthetic steroid derivatives, are used to treat a variety of reproductive disorders. Since synthetic progestogens are often associated with undesirable side effects, improved formulations and modes of administration of progesterone have been sought. In order to find an optimal therapeutic agent, different progesterone formulations and routes of administration have been studied. This paper explains several methods of measuring progesterone levels and summarizes clinical data on the pharmacokinetic profiles of natural progesterone administered by the oral, intramuscular, vaginal, intranasal, percutaneous, sublingual and rectal routes.

Administration, Oral↗
PubMed2000

Anterior hypospadias. Is repair necessary with urination in a sitting or squatting position?

OBJECTIVE: To determine the chronic complication rate of anterior hypospadias repair and to explore whether the practice of placing the neomeatus at the tip of the penis should be applicable to all cases in our community where urination is in a sitting/squatting position. METHODS: Over a 10-year period commencing 1st September 1987, 312 patients had hypospadias repair of whom 72% had anterior hypospadias. The meatus was advanced to the tip of the penis in all repairs. The location of the meatus was also determined in 281 non-complaining men with a straight penis and normal sexual and reproductive functions. Following prior information that anterior hypospadias was not associated with sexual and reproductive dysfunction, 51 patients were given a choice between repair or no repair. RESULTS: Urethrocutaneous fistula occurred in 5% of patients, urethral stricture in 3% and meatal retraction in 3%, with 92% of patients having no complications. Forty six percent of non-complaining men had the meatus in locations other than the tip of the penis. Of 51 patients with the benefit of informed consent, 73% opted for no repair. CONCLUSION: Our results of anterior hypospadias repair compare favourably with those of other centers. Placement of the meatus at the tip of the penis for anterior hypospadias should not be applicable to all patients in this community where urination is in a sitting/squatting position. Before such repairs, an informed consent is warranted by making the patients and their parents aware of the non-association of sexual and reproductive disorders with these anomalies.

Adolescent↗
PubMed2001

A study of insulin resistance in subjects with acanthosis nigricans.

AIM: To study the prevalence of insulin resistance (IR) and its sequelae in patients with acanthosis. METHODOLOGY: Thirty six patients (28 females; eight males) with biopsy proven acanthosis nigricans and eight controls were evaluated for insulin sensitivity (IS) by estimating (a) the glucose and insulin responses to a 75 gm glucose load (Oral glucose tolerance test-OGTT), (b) the glucose disposal rate (GDR) during an intravenous insulin tolerance test (ITT). Serum androgen levels (testosterone--Te, androstenedione--ASD, Dehydro-epiandrosterone sulphate--DHEAS) were estimated in the basal state and 60 min after a bolus of insulin. Thyroid function tests (tri-iodo-thyronine--T3, thyroxine--T4, thyroid stimulating hormone--TSH) were performed in all subjects. RESULTS: The acanthotic population, overall had insignificant hyperglycemia (Area under curve of glucose--AUC-G : 17,745.5 +/- 847.5 v/s 11,051.3 +/- 274.5 mg/dl/min) and hyperinsulinemia (Area under curve of insulin -AUC-I: 20,825.2 +/- 1,287.7 v/s 6,340.1 +/- 984.2 microlU/ml/min) compared to controls during OGTT. Eight patients with acanthosis nigricans had impaired glucose tolerance and eight had overt diabetes using WHO criteria. 69.4% of the acanthotic subjects were obese and 13.9% (5/36) were hypertensive. Thyroid dysfunction was present in three (one had hypothyroidism and two had thyrotoxicosis). Reproductive disorders--menstrual irregularity (46.5%), amenorrhea (21.4%), hirsuitism (21.4%) and infertility (3.6%) was encountered in a significant number of acanthotics. Acanthotics overall had statistically higher levels of androgens; Te (females)--0.74 +/- 0.09 v/s 0.27 +/- 0.09 ng/ml (p < 0.005), ASD--1.8 +/- 0.21 v/s 0.94 +/- 0.2 ng/ml (p < 0.005) and DHEAS--1,880.8 +/- 216.3 v/s 772.8 +/- 210.4 ng/ml (p < 0.005). An elevated DHEAS correlated positively to body mass index (BMI) and android obesity. Serum Te levels correlated positively with GDR. Serum insulin levels increased progressively with obesity and acanthosis. Serum insulin was associated with progressive worsening of hyperandrogenism (as seen in non-obese controls, non-obese and obese acanthotics). CONCLUSIONS: Subjects with acanthosis nigricans should be screened for insulin resistance and its clinical and metabolic sequelae. Thyroid dysfunction should be sought in these subjects as it can be easily treated.

Acanthosis Nigricans↗
PubMed2001

Development of a technique for transcervical collection of uterine tissue in bitches.

Transcervical collection of endometrial tissue specimens is a valuable and well established tool for the diagnosis of reproductive disorders in cows, mares and women, but it is not used currently in bitches. Endometrial biopsy samples were collected by transcervical cannulation from the cranial uterine body at defined stages of the oestrous cycle using biopsy forceps. In study 1, the histology of 45 biopsy specimens taken from 23 Beagle bitches were compared with larger tissue samples collected post mortem. For further evaluation of representative biopsy specimens, the expression of oestrogen and progesterone receptors was determined. Only 31.1% of the biopsy samples taken from bitches could be evaluated and they showed stroma, capillaries, luminal epithelium, glandular ducts and apical glands; however, basal glands and myometrium were not observed. Biopsy findings were in agreement with the diagnosis of the uterine specimens concerning endometrial differentiation, inflammatory and degenerative lesions. The expression of oestrogen and progesterone receptors was slightly lower in the biopsy samples. In study 2, a total of 49 serial biopsy samples were taken from 12 Beagle bitches. In eight bitches, the manipulation resulted in a haemomucometra. Treatment with PGF2 alpha and antibiotics led to a clinical cure in five of these dogs, two of which were mated successfully during the next oestrus. Three animals had to undergo ovariohysterectomy. Owing to the small proportion of biopsy specimens that was suitable for analysis and the high risk of biopsy-related endometritis, transcervical biopsy collection cannot be recommended as a routine technique in bitches.

Animals↗
PubMed2001

Estrogen receptor based in vitro assays for the evaluation of endocrine disrupters.

An increasing number of environmental chemicals is suspected to act similarly as endogenous estrogens at concentrations far below the so called "No Observed Adverse Effect Levels". In man, as in wildlife, these substances are held responsible for several reproductive disorders e.g. the decline in sperm quality and the increase in testicular cancer incidence in different countries worldwide. Several in vitro bioassays have recently been developed to screen single compounds for their ability to bind to estrogen receptors (ER) resulting in a hormone specific response. However, divergent results from these assays indicate the lack of validation and standardisation. Moreover, the proven cell specificity of estrogen response questions the relevance of the observed effects and necessitates the development of assays in a fertility related cellular context.

Animals↗
PubMedDate not supplied

Lipophil-mediated reduction of toxicants in humans: an evaluation of an ayurvedic detoxification procedure.

CONTEXT: Lipophilic toxicants have been associated with hormone disruption, immune system suppression, reproductive disorders, several types of cancer, and other diseases. Due to environmental persistence and bioaccumulation, body burdens of certain toxicants, such as dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs), appear to be a health risk despite the toxicants' having been banned for decades. OBJECTIVE: To determine whether a safe, standardized, Ayurvedic detoxification procedure can mobilize lipid-soluble toxicants and stimulate their excretion. DESIGN: Cross-sectional and longitudinal evaluations. SETTING: Southeastern Iowa. PARTICIPANTS: In the cross-sectional study, 48 participants who had undertaken lipophil-mediated detoxification were compared with 40 control subjects. In the prospective, longitudinal evaluation, serum levels were measured in 15 subjects before and after they underwent the detoxification procedure. These 15 subjects served as their own controls. INTERVENTION(S): Ayurvedic lipophil-mediated detoxification procedure. MAIN OUTCOME MEASURE: Gas chromatographic analysis of 17 serum toxicant levels (9 PCB congeners and 8 pesticides or metabolites) on a lipid-adjusted and wet-weight basis (ng/g) as parts per billion. RESULTS: In the cross-sectional study, gas chromatographic analysis of 9 PCB congeners and 8 pesticides revealed that serum PCB levels were significantly lower in the detoxification subjects than in controls. Trans-nonachlor (TNC), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), oxychlordane, and hexachlorobenzene (HCB) levels were also markedly lower in the detoxification group. All subjects had undetectable levels of p,p'-DDT, lindane, and a-hexachlorocyclohexane (a-HCH). Beta-hexachlorocyclohexane (beta-HCH) levels were significantly higher in detoxification subjects than in controls. In the longitudinal evaluation, after treatment, mean levels of PCBs (46%) and beta-HCH (58%) declined significantly in the subjects. CONCLUSIONS: The higher beta-HCH levels in the subjects in the longitudinal study appear to be an anomaly related to diet. The results of the 2 studies generally suggest that lipophil-mediated detoxification may be effective in reducing body burdens of fat-soluble toxicants. As numerous people worldwide are at risk from high body burdens of such lipid-soluble agents, further studies to evaluate this procedure appear warranted.

Case-Control Studies↗
PubMedDate not supplied

[The hygienic characterization of atmospheric pollution and indices of the health status of females and children under metal processing of naturally alloyed ores].

The agglocoking blast-furnace processing of naturally alloyed ores gives rise higher volumes of dust and gas wastes which on air dispersal yield to higher concentrations of air pollution with dust, sulfur-containing substances, as well as compounds of carbon monoxide, phenol, and ammonia than that of magnetic iron ore, which yields a higher prevalence of comparable forms or reproductive disorders in women and higher general morbidity in children.

Adult↗
PubMed2002

ACOG technology assessment. Genetics and molecular diagnostic testing. Number 1, July 2002. American College of Obstetrics and Gynecology.

Human genetics and molecular testing is playing an increasingly important role in obstetric and gynecologic practice. It is essential that obstetricians and gynecologists are aware of the advances in our understanding of genetic disease and the fundamental principles of molecular testing and genetic screening as genetics is integrated into routine medical practice. In the future, elucidation of the genetic basis for reproductive disorders, common diseases, and cancer with improved high throughput technology for genetic testing will expand testing opportunities and influence treatment options and prevention strategies.

Female↗
PubMed2003

Effects of tributyltin chloride on the reproductive system in pubertal male rats.

Detrimental effects of tributyltin (TBT) chloride on the reproductive system were investigated in pubertal male rats. Sixty Sprague-Dawley rats aged with 35 days were assigned to six different groups; negative control receiving vehicle, positive control receiving methyltestosterone (10 mg/kg B.W.), TBT chloride (5 mg/kg B.W., 10 mg/kg B.W., and 20 mg/kg B.W.), and a combination of TBT chloride (10 mg/kg B.W.) and flutamide (10 mg/kg B.W). The animals were treated with test compounds by oral gavage daily for 10 days and sacrificed on the next day of the final treatment. The treatment with TBT chloride at the doses of 10 and 20 mg/kg B.W. significantly decreased seminal vesicle weights, compared to the negative control. The combined treatment of TBT chloride and flutamide caused a significant decrease in accessory sex organ weights, compared to the control and TBT chloride treatments. The treatment with TBT chloride or in the combination with flutamide increased detached debris and sloughed cells in the tubules of epididymis and narrowed seminal vesicles. In addition, the combined treatment with TBT chloride and flutamide caused a noticeable increase in serum androgen level, compared to the negative control. These results suggest that TBT chloride exposed during pubertal period cause partial reproductive disorders in male rats.

Animals↗
PubMed2003

[Occupational accidents and female workers' reproductive health].

The article covers analysis and summary of data on occupational traumatism among female workers engaged into various economic branches of RF. The authors analysed distribution of victims according to occupational accident types, causes of traumatism, studied dependence on the victims' age and length of service, followed the relationships with possible reproductive disorders.

Accidents, Occupational↗
PubMed2003

[Humoral immune response in breeding sows after vaccination with a herd-specific Chlamydophila abortus vaccine].

A chlamydial vaccine efficacy trial with assessment of the clinical acceptability and serum antibody responses was performed in breeding sows. A BGM cell culture derived vaccine containing 10(8)/ml formalin-inactivated purified elementary bodies (Eb.) in sterile 0.15 M saline was prepared from Chlamydophila (Ch.) abortus strain OCHL03/99 which has been isolated in the herd from a sample of vaginal discharge. Vaccination was performed as a randomised trial with parallel treatment of a vaccinated group (25 sows) and non-vaccinated control group (20 sows). Sows received two 2.0-ml doses of vaccine intramuscularly at a three week interval. Control sows were dosed with sterile 0.15 M saline, accordingly. Serological response to vaccination was measured by ELISA with a total of 204 blood serum samples (114 from the vaccine group; 90 from the control group) using crude chlamydial LPS as the antigen. Compared to the control group, vaccinated sows showed a marked primary and secondary IgG serum antibody response following the two vaccinations. Antibody levels peaked between week 7 and 14 after priming vaccination, declined incrementally until week 27 but remained significantly higher than the corresponding sham-immune control levels and the prevaccination values of the vaccine group (p < 0.05). Western blot analysis of solubilized whole Eb. of Ch. abortus, Ch. pecorum, and Chlamydia (C.) suis with pre- and postvaccination sera confirmed that vaccination induced an antibody response preferentially against a range of 13 chlamydial antigens including the 40 kDa MOMP of Ch. abortus. Clinical side effects consisting of a transient mild local inflammatory reaction at the site of injection were observed in approx. 30% of vaccinated sows. These results provide the basis for further clinical evaluation of the Ch. abortus vaccine to protect sows from chlamydia-induced reproductive disorders.

Animals↗
PubMedDate not supplied

[Vitamin E levels in patients with celiac disease].

BACKGROUND: Coeliac disease (CD) is a genetically linked immune-mediated enteropathy triggered by the ingestion of gluten-containing grains food. Deficiencies of trace elements and vitamins may be found in patients with untreated CD. No systematic studies have been carried out on vitamin E status in coeliacs. Tocopherol deficiency is implicated in the biological processes leading to malignant cell transformations, neurological complications, brown bowel syndrome and reproductive disorders. Untreated patients with CD have higher incidences of these disorders than in general population. AIM: The aim of this study was to investigate vitamin E status in patients with coeliac disease. MATERIAL AND METHODS: We examined retinol plasma level and tocopherol levels both in plasma and in erythrocytes in 18 patients (age: 2-53 years) with active CD and 12 coeliacs (age: 3-36 years) on gluten-free diet without antiendomysium antibodies for at least 2 years. Vitamins were measured by high-pressure liquid chromatography according to the procedure of Driskell. RESULTS: In untreated patients levels of plasma tocopherol (13.7 +/-3.8 micromol/L vs. 20 +/-7.1 micromol/L; p<0.02), erythrocytes tocopherol (1.7 +/-0.45 micromol/L vs.2.89 +/-0.52 micromol/L; p<0.001) and ratio of plasma tocopherol to serum total cholesterol (3.36 +/-0.9 micromol/L vs. 4.24 +/-0.85 micromol/L; p<0.02) were significantly lower compared to those on gluten-free diet. In the all patients with active CD, concentrations of tocopherol in erythrocytes were below the norm (N>2.5 micromol/L). In untreated patients vitamin A levels did not achieve a significant difference in comparison with the coeliacs on gluten-free diet (1.75 +/-0.57 micromol/L vs. 1.97 +/-0.72 micromol/L; p>0.05). The lowest levels of tocopherol (in plasma: 5.7 micromol/L, in erythrocytes: 0.74 micromol/L) and retinol (0.8 micromol/L; N>0.7 micromol/L) were detected in the same patient refusing dietetic treatment for more than 10 years. CONCLUSION: The conventional treatment of CD is gluten-free diet, but monitoring of tocopherol concentrations, especially in erythrocytes, and correction of its deficiency may offer some benefit for patients who fail to adhere strictly to a gluten free-diet or newly diagnosed coeliacs.

Adolescent↗
PubMedDate not supplied

[Spermatogenesis impairment by polychlorbiphenyls: endocrine and paracrine mechanisms of the damage].

Possible role of changed contents of certain cytokines in the genesis of reproductive disorders was studied in an experiment with rats intoxicated chronically by polychlorbiphenyl (PCB) ecopollutants at the total doses of 0.3 g/kg of the body weight (0.05 LD50 and 3 g/kg of the body weight (0.5 LD50). The enzyme immunodetection was used to analyze blood serum, testicle tissues and sperm for interleukin-1beta, interleukin-6, interleukin-4, tumor necrosis factor alpha, and testosterone and estradiol. The experiment showed that chronic PCB intoxication significantly increases the production of pro-inflammatory cytokines and decreases the production of anti-inflammatory cytokines on a background of a sharp testosterone reduction and inversion of the androgen-estrogen profile. Implications of these shifts to steroido- and spermatogenesis are discussed along with cell and molecular mechanisms of cytokine-mediate PCB intoxication.

Animals↗
PubMed2004

[Progress on molecular biology of delta6-fatty acid desaturases].

Polyunsaturated fatty acids (PUFAs) including gamma-linolenic acid are valuable products because of their involvement in several aspects of human health care. GLA has been claimed to play a crucial role in development and prevention of some skin diseases, diabetes, reproductive disorder and others. At present, market demand for most gamma-linolenic acid is growing continually and current sources are inadequate for satisfying this demand due to the significant problems of low productivity, complex and expensive downstream process and unstable quality. Therefore, seeking for alternative sources are demanding. delta6-fatty acid desaturase is the rate-limiting enzyme for the biosynthesis of PUFAs, which catalyses the conversion of linoleic acid and alpha-linolenic acid to gamma-linolenic acid and stearidonic acid respectively. Unfortunately, the structure information on membrane desaturases is scarce because of the technical limitations in obtaining quantities of purified protein and the intrinsic difficulties in obtaining crystals from membrane proteins. With the isolation of the genes coding for delta6-fatty acid desaturase from various organisms, its characteristics will be elucidated gradually. Here we concisely reviewed the recent progress on studies of molecular biology including the cloning of delta6-fatty acid desaturase gene, structure and function, phylogeny and prospects of gene engineering application.

Cloning, Molecular↗
PubMed2005

Farmers and formulations--rural health perspective.

Conventional farming demands excessive use of chemicals in the form of synthetic fertilizers and pesticides, confirming to the norms of Green Revolution. Farmers in general, specifically in the developing countries resort to injudicious and excessive use of pesticides which is linked to the illiteracy and poverty of the rural farming community. Their overriding concern for profitable agriculture, has rendered the health of the farmers at a greater risk of developing dreadful maladies including various type of cancers, reproductive disorders, respiratory, dermal, and neuropsychological problems etc. The possible means of reducing the health risks are discussed, including the global effort to regulate the manufacture, transport and use of highly toxic pesticides. Slow and programmed transition to alternative agriculture and strengthening of farmers' knowledge on health, ecosystem and environment will prove effective.

Agricultural Workers' Diseases↗
PubMed2005

A treatise on hazards of endocrine disruptors and tool to evaluate them.

Hormones mediate a major part of our essential physiological functions. Both endogenous and exogenous compounds and their metabolites are known to act through hormone receptors leading to regulation of endocrine function. The endogenous ligands that control reproductive functions are generally steroids such as 17beta-estradiol, androgens, progesterone, pregnenolone and glucocorticoids. However, exogenous compounds that are structurally and functionally similar gain entry into animals including humans through the diet or by occupational exposures, causing endocrine disruption. In the recent decade, there is a lot of apprehension about the so-called "endocrine disruptors" which are wide spread in the environment, mainly due to unrestricted human activity. These compounds of anthropogenic or natural origin mimic the action of sex hormones and can interfere with the endocrine system. It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine active compounds may be responsible for malformations in the male reproductive tract, crytorchidism, hypospadias, decrease in sperm counts, decreased male reproductive capacity and even testicular cancers. The increasing concern in both public and scientific communities about these abnormalities have prompted the initiation of epidemiological studies to not only identify, but to also analyze the short and long term effects of endocrine disruptors. As a result, a number of assays have been developed and are undergoing validation aimed at high throughput screening of chemical agents that disrupt endocrine activity. This review consolidates the findings of epidemiological studies, particularly in relation to male reproductive disorders and brings to light the various types of in vitro and in vivo models that are available for tiered testing of suspected compounds.

Animals↗