Catamenial insulin reactions treated with a long-acting gonadotropin releasing hormone agonist

Exacerbation of a variety of symptoms during the menstrual cycle is a well-described phenomenon. The exact causes of these changes are poorly understood, and no specific and efficacious therapy has been described. We successfully treated a patient with severe catamenial insulin reactions with a long-acting gonadotropin releasing hormone agonist to suppress menstrual function and added a combination of estrogen and progestin to offset any adverse effect of the resultant hypoestrogenemia for 1 year.     

Tissue inhibitor of metalloproteinase-1 concentrations are attenuated in peritoneal fluid and sera of women with endometriosis and restored in sera by gonadotropin-releasing hormone agonist therapy

OBJECTIVE: To establish tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in peritoneal fluid (PF) and sera of women with endometriosis and compare them to disease-free controls. DESIGN: Prospective randomized study. SETTING: Academic medical center. PATIENT(S): Women with laparoscopically documented endometriosis and disease-free women of reproductive age. INTERVENTION(S): Peritoneal fluid and sera were collected, and some women received gonadotropin-releasing hormone agonist (GnRH-a) therapy for endometriosis. MAIN OUTCOME MEASURE(S): Peritoneal fluid and sera TIMP-1 concentrations were measured with a specific RIA. RESULT(S): The TIMP-1 concentrations were significantly lower in PF and sera of women with endometriosis compared with disease-free women. The GnRH-a therapy restored serum TIMP-1 concentrations. CONCLUSION(S): Aberrant expression and localization of TIMP-1 may derange the proteolytic milieu of the peritoneal cavity and contribute to the etiology and underlying physiologic sequelae associated with endometriosis. Measurement of TIMP-1 in serum may aid in diagnosing endometriosis and assist with monitoring treatment efficacy in women with this disease.     

Resistance of gonadotropin releasing hormone drive to sex steroid-induced suppression in hyperandrogenic anovulation

Women with hyperandrogenic anovulation (HAA) exhibit increased GnRH drive, as evidenced by a faster LH pulse frequency that slows in response to progestin-induced opioidergic tone. To determine whether increased GnRH-LH drive in HAA reflects altered sex steroid exposure caused by chronic anovulation or is an intrinsic hypothalamic attribute, we compared the pulsatile LH response to oral contraceptive (OC)-induced suppression in seven women with HAA, with that of seven eumenorrheic women (EW). LH levels were determined at 10-min intervals for 12 h after 19-21 days of OC use and 5-7 days after cessation. Testosterone, androstenedione, estradiol, FSH, and LH levels were determined at weekly intervals before, during, and after OC use. LH pulse number/12 h was higher (P < 0.001) in HAA during and after OCs, when compared with that of EW. Mean LH was increased in HAA before, during, and after OCs. Testosterone, androstenedione, and estradiol levels were higher in HAA before OCs, but they decreased to similar levels during OC use in both groups. FSH concentrations were similar before and during OCs but rose more after cessation of OCs in EW. These findings indicate that GnRH drive in HAA is resistant to OC-induced suppression and, therefore, could be an intrinsic hypothalamic attribute.     

Gonadotrophin hormone releasing hormone agonist in cases of severe paraphilia: a lifetime treatment?

Six patients with severe paraphilia were treated with a long-acting gonadotrophin hormone releasing hormone analogue (GnRH-a). In five cases, the antiandrogen treatment ended their deviant sexual behaviour and markedly decreased their sexual fantasies and activities without significant side-effects. The beneficial effects of this treatment were maintained for 7 years in the patient where there was the longest follow-up. Two patients abruptly withdrew front their antiandrogen treatment at the end of the first and third year, respectively. Both relapsed within 8-10 weeks. One of them asked for resumption of antiandrogen treatment. In another case, in order to phase out antiandrogen treatment, testosterone (T) was added to the GnRH-a. In spite of normal T levels, and of resumption of normal sexual activities and deviant fantasies, deviant sexual behaviour did not return. A smoother phasing out of GnRH-a treatment is thought to be better than an abrupt withdrawal. However, the duration of antiandrogen treatment necessary to ensure a complete disappearance of deviant sexual behaviour remains uncertain, but is at least 4 years.     

The role of cyclic adenosine monophosphate in the suppression of cellular immunity after thermal injury

BACKGROUND AND OBJECTIVE: Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is known to convey inhibitory signals for T-cell proliferation and function. We investigated the association between this molecule and the profound immunosuppression that accompanies thermal injury. DESIGN: Mice were randomized into two groups: one group was subjected to a 20% full-thickness scald burn; the second to a sham burn (control). The mice were killed on days 4, 7, or 10 after the burn injury and splenocytes were pooled and cultured for 15 minutes in the presence or absence of prostaglandin E2 (PGE2). RESULTS: Levels of cAMP in splenocytes were significantly elevated on day 7 after burn in the burn group compared with the sham controls (P < .05, Wilcoxon Rank Sum Test). Incubation of splenocytes with PGE2 resulted in significantly greater levels of intracellular cAMP in cells from the burn group compared with controls on days 4, 7, and 10. Incubation of normal splenocytes with dibutyryl cAMP in the presence of concanavalin A significantly decreased cell proliferation and the production of interleukin-2. The decrease in interleukin-2 production was evident at the level of messenger RNA expression. Stimulation of splenocytes with a combination of phorbol ester and calcium ionophore, bypassing all membrane-associated events prior to protein kinase C activation, reversed the inhibitory effects of dibutyryl cAMP. Incubation of splenocytes from burned animals with H-8, a selective inhibitor of cAMP-dependent protein kinases, restored the proliferative response to that of sham controls on days 4, 7, and 10 after thermal injury. CONCLUSIONS: These data indicate that elevated levels of intracellular cAMP, combined with an increased production of cAMP in response to circulating PGE2, may play a fundamental role in suppression of the immune response following thermal injury and that cAMP exerts its immunomodulatory effects prior to protein kinase C activation.     

The state of cellular immunity in women with a history of viral hepatitis

Overall sixty puerperants were examined with a history of viral hepatitis before true pregnancy has set in, with 50 healthy puerperants being controls. In women with prior viral hepatitis, the B-cell link of immunity was found out to be disordered, especially so postpartum, as evidenced by investigations designed to study the chief classes of immunoglobulin G, A, M in parturient women's blood sera and the postpartum complications patterns.     

Cortical remodeling following suppression of endogenous estrogen with analogs of gonadotrophin releasing hormone

The effects of estrogen suppression on osteonal remodeling in young women was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosphatase (ALP) 116%, p = 0.043) but not those showing tartrate-resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in canals with diameters greater than 50 microns (p = 0.0089) and also the number of osteons with diameters over 250 microns (p = 0.049). ALP activity in individual osteoblasts was increased but not significantly following treatment (p = 0.051). Wall thickness was significantly correlated with osteon diameter (p < 0.001). In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption. Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an increase in the osteon diameter. As previously shown for cancellous bone, estrogen withdrawal increased cortical bone turnover. We have now shown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrogen withdrawal in agreement with theoretical arguments advanced previously. Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdrawn may allow the development of new strategies for preventing postmenopausal bone loss.     

Elevation of the phospholipase A2 activity in peritoneal fluid cells from women with endometriosis

OBJECTIVE: To assess the prostaglandin (PG) production on peritoneal fluid (PF) cells, phospholipase A2 (PLA2) activity of those cells in women with endometriosis was measured and compared with that of women without endometriosis. DESIGN: Prospective clinical controlled study. PATIENTS: Women who underwent laparoscopy and were found either to have endometriosis (n = 15) or not (n = 9) were included in this study. Mononuclear cells obtained from the patients at laparoscopy were immediately separated by a Ficoll-Paque technique, lysed by nitrogen cavitation, and stored at -80 degrees C. INTERVENTIONS: Phospholipase A2 activity was measured by Dole assay using 1-palmitoyl-2-[1-14C] palmitoyl phosphatidyl choline and assessed on a protein basis and a cell number basis. RESULTS: There were at least four measurable kinds of PLA2 activity detected in the cells: two calcium-dependent pH optima 7.0 and 9.0 activities and two calcium-independent pH optima 7.5 and 8.5 activities. A calcium-dependent and pH optima 9.0 activity was the highest, and it was significantly higher in women with endometriosis when compared with those who did not have endometriosis. CONCLUSION: These results indicate that the increase in the PGs in PF with endometriosis may be produced by PF cells in which PLA2 activity is elevated.     

Evaluation of autoantibodies against oocyte theca cells in peritoneal effusion and serum of women with endometriosis

The aim of the study was evaluation of presence of the antibodies against theca of the oocyte in peritoneal effusion and in serum in fertile and infertile women with minimal endometriosis in luteal phase of the menstrual cycle. Antibodies were measured by means of ELISA method. Median of the antibodies against theca was three-fold higher in peritoneal effusion in infertile women. No differences were stated in serum.     

Decreased sensitivity to insulin during treatment with danazol in women with endometriosis

Reconstruction techniques for major vessels and intracardiac defect repair use synthetic grafts or autogenic pericardium. Here, autologous abdominal parietal peritoneum with the overlying posterior rectus sheath as a biologic membrane are evaluated. Twelve adult canines were used. Via a midline subumbilical incision, the parietal peritoneum and overlying posterior rectus sheath were harvested. In the first group of six, the membrane was used to repair the right ventricular infundibulum and perform pulmonary artery annuloplasty. In the second group of six, under cardiopulmonary bypass and moderate hypothermia, the right atrium was opened and a secundum type defect was created. Autopsies performed 90 days after surgery revealed mild intrapericardial adhesions and moderate pericardial reaction over the cardiotomy incisions. The right ventricular outflow tract patch was nonaneurysmal. The interatrial patch was intact without thrombi. Histologic examination revealed intact membrane morphology, fibroblasts, smooth muscle cells, and endothelialization. Proline C14 uptake and autoradiography detected cellular viability of implanted membranes. These findings suggest that the peritoneum with overlying sheath repaired vascular and intracardiac defects and substituted for pericardium. Future studies are needed before clinical use.     

Examination of 17 beta-estradiol and progesterone levels in peritoneal fluid and blood serum of women with endometriosis

Authors have presented and assessment of estradiol and progesterone levels in peritoneal fluid and blood serum in women with endometriosis. Peritoneal fluid was collected during laparoscopy performed in luteal phase of the cycle. In this cycle ovulation was controlled in all women. An ovulation was confirmed ultrasonographically and laparoscopically in 45% of women with endometriosis and in 80% of that without the illness. Progesterone concentration in peritoneal fluid in women with endometriosis was significantly lower to the control (p < 0.01).     

Neuropeptide Y and luteinizing hormone releasing hormone synergize to stimulate the development of cellular follicle-stimulating hormone in the hamster adenohypophysis

Luteinizing hormone releasing hormone (LHRH) stimulates the development of cellular FSH immunoreactivity in the perinatal hamster adenohypophysis. Because neuropeptide Y (NPY) can act directly on rat adenohypophysial cells to stimulate FSH and LH release and potentiate the stimulatory effect of LHRH on FSH and LH release, we investigated the effects of NPY alone and in combination with a low, ineffective dose of LHRH on inducing cellular FSH immunoreactivity in the neonatal hamster adenohypophysis. Neonatal female pituitary glands were grafted beneath the right renal capsules of hypophysectomized-ovariectomized adult hamster hosts with a catheter implanted in the external jugular vein. After treatment, hosts were decapitated and graft tissue was stained for FSH and LH immunoreactivity. The mean percentage of adenohypophysial cells that stained for FSH was low (2.8%) in grafts in hosts infused continuously with heparinized saline vehicle for 7 days. In other hosts, peptides were pulsed through the catheter every 12 h for 7 days. The mean percentage of FSH cells also was low after pulsing 6 ng LHRH or 2 micrograms NPY but increased substantially when the two peptides were pulsed simultaneously. No differences in the mean percentage of LH cells existed between any of the groups. The results demonstrate that NPY and LHRH can synergize to induce cellular FSH immunoreactivity in the neonatal female hamster.     

Pregnancy and birth after high serum progesterone concentrations during the follicular phase in an in-vitro fertilization cycle with gonadotrophin-releasing hormone agonist suppression

This case illustrates the possibility of achieving a pregnancy and birth when elevated progesterone concentrations (> 4 ng/ml) are present during the follicular phase (from 6 days before human chorionic gonadotrophin injection) of a gonadotrophin-releasing hormone agonist/menotrophin cycle for in-vitro fertilization (IVF). The present patient underwent three IVF/embryo transfer cycles in which progesterone concentrations were repeatedly increased from the midfollicular phase onwards. A pregnancy was achieved after the first IVF attempt but ended in a miscarriage in the 19th week of gestation. During the second IVF attempt an endometrial biopsy taken on the day of oocyte retrieval revealed an endometrial advancement of 2 days. A successful pregnancy and birth was again achieved after the third IVF attempt although progesterone concentrations were considerably increased from 6 days before the ovulatory stimulus.     

Application of gonadotropin releasing hormone in dairy herds with fertility disturbances with regard to milk yield data and metabolic parameters]

The presented study was made to determine the factors influencing the fertility supporting effect of GnRH application at the time of insemination in a dairy herd with fertility problems. The metabolic parameters considered influencing conception results were milk yield, milk protein and milk fat and for blood parameters Urea, GOT and Bilirubin. The total effect of GnRH consisted in an improved pregnancy rate by 18.8% compared to the non treated control group. The improvement of pregnancy rate was observed mainly in groups with an adequate supply of energy at the time of insemination. Therefore the use of GnRH at insemination time is more successful, when milking test data and blood parameters are taken into account and indicate an equilibrated supply in energy. To explain these effects endocrinological regulation models are discussed.     

The status of the gonadotropin releasing hormone test in differential diagnosis of delayed puberty in adolescents over 14 years of age

BACKGROUND: In patients with delayed puberty with a bone age less than 11 years in girls or 12 years in boys, the clinical and endocrinological examination allows the differentiation of patients with the various forms of hypergonadotropic hypogonadism, but not of patients with hypogonadotropic hypogonadism from more prevalent constitutional delay in puberty. Therefore, watchful waiting is generally recommended for differential diagnosis in patients with delayed puberty. On the other hand, the late onset of sexual hormone replacement in patients with hypogonadism will worsen their outcome. PATIENTS AND METHOD: Therefore, we decided to carry out a retrospective study in 105 adolescents who were examined because of short stature or delayed puberty, who were aged 14 to 22 years at first visit and in whom the differential diagnosis of delayed puberty was documented after an at least one-year follow-up in order to find out which endocrinological parameters could have effectively predicted the final diagnosis already at the first visit. RESULTS: Patients with hypogonadotropic hypogonadism differed from patients with constitutional delay in puberty by lower responses of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to gonadotropin-releasing hormone stimulation (GnRH, 100 micrograms iv) (p < 0.01) as well as by smaller testicular volume (p < 0.05) and by lower testosterone levels (p < 0.01). Stimulated LH < 10 mU/ml differentiated patients with hypogonadotropic hypogonadism from constitutional delay in puberty with a sensitivity of 82% and a specificity of 98%. CONCLUSION: In patients with delayed puberty aged 14 years and older bone age usually exceeds 11 years in girls or 12 years in boys. It thus is in the range, in which normal adult responses of LH to GnRH can be expected. In contrast to patients aged less than 14 years, therefore, measuring GnRH-stimulated LH levels in these patients allows the rapid and effective differential diagnosis of delayed puberty.     

Suppression of luteinizing hormone in castrated women by the administration of human chorionic gonadotropin

The suppressive effect of human chorionic gonadotropin (hCG) on luteinizing hormone (LH) and/or LH-beta was studied by specific LH-beta radioimmunoassay following hCG administration. Eight castrated women were each administered 10,000 IU of hCG in a single intramuscular injection and five women in the control group were injected with saline. The serum level of hCG increased after the injection, reaching 217.6 mIU/ml after 8 h. There was a significant suppression of LH levels as compared to those of the control group and the pre-injection levels: 68.2% 1 h after injection, 64.7% after 2h, 65.5% after 4 h, 77.0% after 8 h, 78.6% after 12 h, and 78.2% after 24 h. There was no significant suppression of the follicle-stimulating hormone (FSH) as compared to the preinjection and control values. Serum concentration of estradiol1 was not detectable either before or after the hCG injection. We conclude that hCG has a suppressive effect on LH and/or LH-beta secretion not mediated by estradiol.     

The midcycle gonadotropin surge in normal women occurs in the face of an unchanging gonadotropin-releasing hormone pulse frequency

The midcycle gonadotropin surge is a critical event in normal reproductive cycles and requires functional integration of the hypothalamus, pituitary, and ovary. To determine whether a change in GnRH frequency occurs coincident with the onset or termination of the surge in normal women, 20 studies were performed at a sampling interval of every 5 min for up to 36 h. The frequency of pulsatile GnRH secretion was assessed by the use of two surrogate markers of its secretion, LH and free alpha-subunit (FAS). The timing of the studies was prospectively determined by serial ultrasound and previous cycle history, whereas measurements of LH, FSH, estradiol, and progesterone in daily blood samples were used retrospectively to locate the frequent sampling study in relation to the day of ovulation in each individual. The frequent sampling studies were divided into late follicular phase (LFP; days -4 to -2) and early, mid-, and late portions of the midcycle surge (days -1 to 1) in relation to the 95% confidence limits of the LH peak derived from daily samples in 69 normal ovulatory women. The patterns of LH and FAS secretion were pulsatile at all times during the midcycle surge. The amplitude of LH pulsations increased from the LFP and early surge to the midportion of the midcycle surge (5.9 +/- 6 and 15.1 +/- 5 vs. 39.0 +/- 3 IU/L; P < 0.0001) and decreased from the mid- to the late portion of the surge (13.4 +/- 5 IU/L; P < 0.0001). Likewise, the amplitude of FAS pulse increased from the LFP and early surge to the midportion of the surge (82.4 +/- 59 and 153.1 +/- 50 vs. 421.4 +/- 35 ng/L; P < 0.0001) and decreased from the mid- to the late portion of the surge (190.8 +/- 49 ng/L; P < 0.0002). Although there was excellent concordance of pulsatile secretion of LH and FAS, significantly more pulses of FAS were detected than of LH (P < 0.0001). There was no change in frequency (expressed as interpulse interval) between the LFP and the early and midportions of the surge for LH (70.0 +/- 8, 67.5 +/- 7, and 65 +/- 5 min, respectively) or FAS (55.1 +/- 7, 54.6 +/- 6, and 60.0 +/- 4 min). However, there was an increase in LH interpulse interval (decrease in pulse frequency) in the late portion of the surge (87.0 +/- 6 min) compared to the early and midportions of the surge (P < 0.02 and P < 0.0005, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)