Serum profile of gonadotropins and ovarian steroids in women during six months of treatment with ORG 485-50

The effect of Org 485-50¹ on endocrine parameters of the pituitary and ovarian function has been studied in seven healthy women. Daily serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol-17β and progesterone were measured by specific radioimmunoassay throughout the control and seventeen treatment cycles during a drug trial period of six months. The results show that Org 485-50 at this dose caused anovulation in seven medication cycles. All other treatment cycles had a significant, though variable, suppression of progesterone secretion. The biphasic pattern of estradiol secretion was similar in control and medication cycles, but the overall output of estradiol decreased during prolonged treatment. Midcycle LH surge was abolished in seven and impaired in ten of the treatment cycles. It is noteworthy that the alteration of the hormone profiles caused by Org 485-50 was markedly different between the individuals. The changes of the endocrine parameters indicative of anovulation or inadequate corpus luteum function were, in different individuals, constant or variable during treatment with Org 485-50.     

Plasma and urinary steroids in pregnant women during p-aminoglutethimide treatment

p-Aminoglutethimide, a known inhibitor of adrenal steroid biosynthesis, was administered to five women in the 9–13th week of pregnancy. Increased uterine contractility was observed in four subjects and uterine bleeding was seen in one of the patients. Analysis of plasma progesterone, urinary estriol and 19 plasma and 27 urinary neutral steroid sulfates indicated that progesterone biosynthesis and the biosynthesis of certain maternal adrenal steroids was partly inhibited by this treatment. Fetal steroid biosynthesis also seemed to be impaired by the administration of this drug.     

Further studies on pituitary and ovarian function in women receiving hormonal contraception

Pituitary and ovarian function was evaluated in women receiving 3 combined oral contraceptive preparations. Basal levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) and gonadotropic responses to gonadotropic releasing hormone (GnRH) were studied in 36 healthy, regularly ovulating women in the early follicular and mid-luteal phases of their menstrual cycle (non-treatment, control). These same women were then divided into 3 groups with 12 volunteers in each. Each group received an oral contraceptive preparation cyclically for 3 months. The preparations were: Nordette (30μg ethinyl estradiol and 150 μg d-norgestrel), Nordiol (50μg ethinyl estradiol and 250μg d-norgestrel) and Biphasil (50μg ethinyl estradiol and 50μg d-norgestrel × 11 days and 125μg d-norgestrel × 10 days). In the third month of treatment, the tests were repeated on day 21, i.e. after 21 active pills, and on day 28, i.e. after 21 active and 7 inactive tablets. On active therapy, basal FSH and LH were similarly suppressed in the 3 groups. LH had varied responses to a bolus of GnRH, whilst the FSH responses were similar in the 3 groups. After 7 days of inactive tablets, basal FSH and LH had returned to pre-treatment, early follicular phase levels. However, the LH responses to a bolus of GnRH varied in the 3 groups, but again, no differences were noted in the FSH responses. Basal FSH, LH and E2 recovered earlier in the Nordette group during the 7 days of inactive tablets.     

Serum gonadotropin and ovarian steroid levels in women during administration of a norethindrone-ethinylestradiol triphasic oral contraceptive

We studied the inhibitory effect of a triphasic oral contraceptive (OC) regimen on the pituitary and ovarian function in 29 normal, healthy women. ORTHO* 7/7/7 Tablets contain a constant low dose of ethinylestradiol (EE) and a step-wise increasing level of norethindrone (NE). The pills for the first, middle and last weeks of the 21-day regimen contained, respectively, 0.5, 0.75, and 1.00 mg NE, and all contained 0.035 mg EE. The subjects were divided into 3 groups on the basis of their histories of OC use. Ten had not taken an OC in the previous 2 months, 10 were switched to this study from a fixed-dosage combination OC containing 0.050 mg estrogen, and 9 had been taking ORTHO 7/7/7 Tablets for 5 or more cycles. Serum levels of FSH, LH, estradiol and progesterone were measured and statistically compared with those from 5 normal, untreated women. The results from all study cycles showed that the four hormone profiles were significantly suppressed as compared to the normal patterns. Thus, one mode of action of this new triphasic OC is to inhibit ovulation by suppression of pituitary-ovarian function. This OC treatment appeared to be equally effective among women with varying prior histories of OC therapy.     

Lead poisoning and reproduction: effects on pituitary and serum gonadotropins in neonatal rats.

In order to investigate the effects of neonatal lead poisoning on pituitary gonadotropic function, newborn rats were given daily doses of lead (25, 100, and 200 mg/kg) by gastric gavage. Control rats were given deionized water. Groups of animals were sacrificed at 10, 15, and 20 days of age and serum and pituitary levels of the gonadotropins follicle stimulating hormone (FSH) as well as pituitary contents of luteninizing hormone (LH) were determined by radioimmunoassay. Lead concentrations in blood, bone, brain, and pituitary tissues of similarly treated 15-day-old rats were determined by atomic absorption spectrometry. Lead content in bone (femur) and brain showed dose-dependent elevations throughout the dose range; in blood, it reached a plateau of about 1000 μg% already at the dose of 100 mg/kg/day. Lead remained at undetectable levels (<0.01 μg/g) in pituitary tissue regardless of the dose. There were no significant differences between lead-treated and control rats in body weights, pituitary weights, pituitary LH contents in either sex, and serum FSH levels in males. Lead exposure increased pituitary FSH content in male rats at all ages studied, and suppressed serum FSH levels in 15-day-old females. These results suggest that the effects of subclinical neonatal lead poisoning on gonadal development and subsequent function, especially in the female, may be mediated by central neuroendocrine mechanisms.     

Correlation of plasma gonadotrophins and ovarian steroids pattern with symptomatic changes in cervical mucus during the menstrual cycle in normal cycling women

27 healthy young Italian women were studied to evaluate their ability to identify symptomatically the potentially fertile phase of the menstrual cycle by self observation of their cervical mucus pattern as described in the Ovulation Method Billings.

The women's observations were correlated with daily plasma levels of FSH, LH, estradiol-17ß and progesterone.

Ovulation was considered to occur on the day following the LH peak.

The hormonal assays revealed that 2 of the 34 cycles studied were anovulatory.

24 of the 27 subjects in the study group demonstrated their ability to recognize the onset of the mucus discharge and the peak symptom from the first cycle after teaching, another two from the second cycle. The only other subject contributed an anovulatory cycle in which the hormonal assay confirmed the accuracy of her mucus observations.

In the study, the mean interval between the time of ovulation as assessed and the peak symptom recorded by the subjects was 0.0 days, with a range from -2 to +1 days. The mean time interval from the first recorded symptom to the estimated day of ovulation was 6.0 days, with a range from 3 to 10 days.

The study shows that young Italian women can be taught to recognize their cervical mucus pattern as described in the Ovulation Method Billings. The accuracy of their observations is demonstrated by the hormonal assays. The study also confirms the conclusion reached in earlier similar studies that there is a direct correlation between the cervical mucus symptom and the potentially fertile phase of the cycle.

Research is currently being conducted on a larger number of couples employing the Ovulation Method Billings to actually regulate their fertility.     

Genetic profile of Glanzmann's thrombasthenia in south Tunisia. Report of 17 cases (11 families)

INTRODUCTION: Glanzmann's thrombasthenia (GT) is a rare congenital thrombopathy, with a recessive autosomal transmission. We present here the genealogic study of a series of patients suffering from GT. PATIENTS AND METHODS: This is a retrospective study about all the GT patients treated in Sfax hematology department during 18 years. Final diagnosis was established by agregometry. Genealogic study was based on clinical history. RESULTS: 17 cases of GT from 11 families from the south of Tunisia wen collected. The disease was paricularly frequent in the region of Moulares-Gafsa (7 patients). The percentage of consanguinity was also very high (82%), with a third degree consanguinity of 86%. Family investigation revealed 6 previously unknown cases, and 10 deaths subsequent to hemorrhagic manifestations. CONCLUSION: The high rate of consanguinity, the absence of clinical or biological manifestations in the parents, and the ratio of ill to normal subjects in the same family which was about one to four, are suggestive of an autosomal recessive mode of transmission.     

Discriminatory effect of anti-Pr-beta-hCG-TT antibodies on the neutralization of the biological activity of placental and pituitary gonadotropins.

In 2 test systems, serum from monkeys and human subjects immunized with an anti-human chorionic gonadotropin (hCG) vaccine, Pr-beta-hCG-TT, were analyzed for their capacities to neutralize hCG/luteinizing hormone (LH)-induced biological effects. hCG-induced ovulation was completely blocked by the monkey antiserum in mice, but the same amount of antiserum, and even 2-fold greater concentrations, did not reduce the number of ovulating animals when primed with ovine LH. Competency of both the immunized monkey and human sera to neutralize the hCG-induced testosterone production in Leydig cells was shown. All monkey and 7/12 human sera did not interfere with the human LH action on Leydig cells. 5 human sera, however, showed varying degrees of inhibition of human LH-induced sterodogesnesis by this sensitive Leydig cell bioassay. Nevertheless, these subjects maintained regular menstrual cycles, and serum progesterone levels during the luteal phase were consistent with ovulation. Normal hormone profiles were constructed from a subject whose serum had shown a fairly high degree of cross-reaction with human LH by the Leydig cell bioassay when estradiol, human LH, and progesterone levels were determined on different days throughout the menstrual cycle.     

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women.

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.     

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: 1. Dynamic changes during the periovulatory period

In order to assess the periovulatory interrelationships between the plasma levels of estradiol, estrone, 17-hydroxyprogesterone, progesterone, cortisol and biologically active lutropin (LH), peripheral blood samples withdrawn from 12 normally menstruating women at 07.00, 15.00 and 23.00 h. during seven days of the midcycle period were analyzed.The estradiol peak varied between 0.86 and 1.50 nmol/l; it preceded the LH peak in 11 subjects and occurred simultaneously with it in 1 case. Although the peak levels of estradiol were significantly higher than those associated with the LH peak, there was no significant difference between the estradiol levels at the LH peak and those found during the 32-hour period prior to the LH peak.Calculation of the estradiol to estrone ratios revealed the existence of two groups of subjects with significantly different ratios. In one group the estradiol levels were significantly lower and those of estrone significantly higher than in the other group. No difference was found between these two groups concerning the other hormonal indices measured.No significant variation was found in the estradiol, estrone and LH levels during the day; however, there was a significant overnight increase in their levels during 3 to 4 days preceding the day of the LH peak.A significant rise in 17-hydroxyprogesterone levels occurred 8 h. before the earliest rise in LH and progesterone levels; on the other hand, in none of the subjects did the first rise in progesterone levels precede the first significant elevation of LH levels.     

Pituitary and ovarian function in women receiving hormonal contraception.

A study was performed to further evaluate pituitary-ovarian function in women receiving an oral contraceptive preparation. Basal hormone levels (follicle stimulating hormone, luteinizing hormone, estradiol and prolactin) and gonadotropic response to gonadotropic releasing hormone were studied in 12 healthy, regularly ovulating women in the early follicular and mid-luteal phases of their menstrual cycle (non-treatment control period). These same women were then given NORDETTE (ethinyl estradiol 30 microgram +d-Norgestrel 150 microgram) cyclically for 3 months. In the third month of treatment, the tests were repeated on day 21, i.e. after 21 active pills, and on day 28, i.e. after 21 active and 7 inactive tablets. On active preparation, basal luteinizing hormone, follicle stimulating hormone and estradiol and gonadotropin response to gonadotropin releasing hormone were significantly suppressed. However, by day 28 (after completion of the inactive tablets), basal gonadotropin and estradiol concentrations and the gonadotropic response to gonadotropic releasing hormone were not significantly different to their pretreatment levels. No consistent change in prolactin concentration occurred as a result of oral contraceptive therapy. These results indicate that the 'active' component of even a relatively low-dose pill causes considerable suppression of pituitary-ovarian function but that after 7 days of placebo, pituitary function and basal estradiol secretion have virtually returned to normal.     

Plasma levels of norethindrone and effect upon ovarian function during treatment with silastic implants containing norethindrone.

The study was made to evaluate the effect upon the ovarian steroid pattern during treatment with subcutaneously implanted silastic rods containing norethindrone. Four rods, each containing 37 mg norethindrone (NET), were implanted subcutaneously in five women and left in place for 135--200 days. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. After an initial peak found in all subjects, the plasma level of NET declined. Great day-to-day variations of NET were found. Ovulations were suppressed during treatment in three subjects. One subject had regular ovulations throughout treatment and in one subject a single ovulation was recorded. Peaks of estradiol without subsequent ovulation were found in two subjects. The bleeding pattern was irregular; three subjects had varying degrees of spotting and bleeding, two subjects were amenorrheic. The average daily release rate was 300/micrograms, calculated from the amount of steroids lost from the removed rods. This study indicates that the release of steroid from four NET rods is high enough only initially to completely inhibit ovulation.     

Clinical profile and toxicology studies on four women immunized with Pr-beta-HCG-TT.

Clinical profile and toxicology studies on 4 women immunized with processed beta human chorionic gonadotropin conjugated to tetanus toxoid (Pr-beta-HCG-TT) are presented. The women responded to active isoimmunization by production of anti-hcg and anti-TT antibodies. The women were followed for 1 year with monthly clinical examinations including laboratory hepatic function tests, renal function tests, metabolic studies, endocrinal studies, and hematological studies. No abnormality was seen, indicating that active isoimmunization with Pr-beta-HCG-TT has no adverse or undesirable side effects in women of childbearing age.     

Hepatic glutathione, metallothionein and zinc in the rat on gestational day 19 during chronic ethanol administration

Ethanol, under certain conditions, alters the metabolism of sulfur amino acids, metallothionein (MT) and zinc. If chronic ethanol administration during pregnancy decreases the availability of sulfur amino acids or Zn, this deficiency could contribute to growth retardation of the fetuses, one of the features of fetal alcohol syndrome. The purpose of this study was to discern whether chronic ethanol administration to pregnant rats alters glutathione (GSH), MT or Zn content of selected tissues of the dams and fetuses. Sprague-Dawley rats were fed from gestational days 5 to 19 either the control diet ad libitum (AF), the ethanol diet ad libitum (EF) or the control diet using the pair-feeding technique (PF). On the 19th day of gestation, total hepatic GSH was significantly lower for the EF and PF dams than for the AF dams. Hepatic MT contents were similar for the AF and EF dams, and hepatic MT content was significantly greater for the PF dams than the AF and EF dams. The three groups did not differ regarding hepatic Zn content of dams or fetuses. In summary, on the 19th day of gestation, chronic ethanol feeding of pregnant rats did not lower the maternal hepatic GSH level below that of PF dams, did not induce hepatic MT in the dams and did not prevent fetuses from achieving body weights and hepatic Zn concentrations equal to those of controls.     

Plasma levels of d-norgestrel and ovarian function in women using intravaginal rings impregnated with dl-norgestrel for several cycles

Silicone polymer intravaginal rings (IVR) of a new “shell” design were used in the present study. The steroid containing part of the rings was impregnated with different amounts of dl-norgestrel. The rings were designed to give two different release rates. Forty-one treatment cycles were studied. The mean plasma level of d-norgestrel, as measured by radioimmunoassay, varied between 2.6 and 0.3 ng/ml. The highest levels were found during the first treatment cycle and declined thereafter. No correlation could be found between the plasma levels of d-norgestrel and the release of d-norgestrel from the rings.Signs of ovulation occurred in 6 (15 %) and breakthrough bleeding or spotting was encountered in 26 (63 %) of the cycles. Breakthrough bleeding and spotting was a constant finding in cycles with a mean plasma level of d-norgestrel below 1.1 ng/ml but never appeared in cycles with a mean level above 1.7 ng/ml. No effects on vaginal flora or the vaginal smear were found.Although the high frequency of bleeding irregularities casts doubt on the acceptability of the IVRs used in this study as a contraceptive method, the study has shown that it is possible to design IVRs capable of releasing dl-norgestrel for several consecutive cycles at fairly constant rates and in amounts sufficient to inhibit ovulation.     

Effects of low steroid doses administered in the mid and late follicular phase on the LH surge, ovarian steroids and follicular maturation in eumenorrheic women

The effects of four low doses of synthetic steroids, administered orally and starting on day 8 (group I) or on day 10 of the menstrual cycle (group II), upon LH surge, ovarian steroidogenesis, follicular maturation and menstrual cycles were studied in 10 eumenorrheic women.The results revealed that the day before the LH surge, the highest level of estrone-3-glucuronide was observed in both groups. Twenty-four hours after the last dose, the maximum urinary LH levels were recorded in groups I (day 11), and II (day 13). Pregnanediol-3 glucuronide remained low during the study in group I, whereas in group II a gradual rise of this hormone starting on day 13 was registered and the highest level was found at day 21 of the menstrual cycle. Follicular maturation and ovulation were observed only in women from group II. Short and normal length cycles were recorded in groups I and II, respectively.In summary, low doses of exogenous synthetic steroids administered on day 8, but not on day 10 of the cycle, inhibit follicular maturation and ovulation.     

Lipid profile and socioeconomic status in healthy middle aged women in Sweden.

STUDY OBJECTIVE: To examine the relationship between socioeconomic status (SES) and full lipid profile in middle aged healthy women. PARTICIPANTS: These comprised 300 healthy Swedish women between 30 and 65 years who constitute the control group of the Stockholm female coronary risk study, a population based, case-control study of women with coronary heart disease (CHD). The age matched control group, drawn from the census register of greater Stockholm, was representative of healthy Swedish women aged 30-65 years. Five measures of SES were used; educational level, occupation, decision latitude at work, annual income, and size of house or apartment. MAIN RESULTS: Swedish women with low decision latitude at work, low income, low educational level, blue collar jobs, and who were living in small houses or apartments had an unhealthy lipid profile, suggesting an increased risk of CHD. Part of this social gradient in lipids was explained by an unhealthy lifestyle, but the lipid gradients associated with decision latitude at work and annual income were independent of these factors. Decision latitude, educational level, and annual income had the strongest associations with lipid profile. These associations were independent of age, menopausal status, smoking, sedentary lifestyle, alcohol consumption, obesity, excess abdominal fat, and unhealthy dietary habits. Of the lipid variables, low high density lipoprotein cholesterol (HDL) levels were most consistently associated with low SES. CONCLUSIONS: Decision latitude at work was the strongest SES predictor of HDL levels in healthy middle aged Swedish women, after simultaneous adjustment for other SES measures, age, and all lifestyle factors in the multivariable regression model.     

多囊卵巢综合征患者脂联素及脂联素受体表达的对照研究

目的:探讨不同表现型多囊卵巢综合征(PCOS)患者血清和卵泡液中脂联素水平及黄素化颗粒细胞脂联素、脂联素受体mRNA表达的差异,及其对卵子成熟和IVF结局的影响。方法:随机选择行体外受精-胚胎移植(IVF-ET)的71例患者并分4组,第1组为肥胖PCOS组(BMI>24kg/m2)14例,第2组为正常体重PCOS组(BMI≤24kg/m2)22例,第3组为肥胖非PCOS组(BMI>24kg/m2)17例,第4组为正常体重非PCOS组(BMI≤24kg/m2)18例。采用酶联免疫吸附法(ELISA)测定采卵日血清和卵泡液中脂联素蛋白表达水平,逆转录聚合酶链反应(RT-PCR)半定量测定卵巢黄素化颗粒细胞脂联素、脂联素受体mRNA的表达水平。结果:两组PCOS患者血清与卵泡液中脂联素及颗粒细胞脂联素受体水平与相应对照组无差异;肥胖患者(PCOS或非PCOS)中血清脂联素与颗粒细胞脂联素受体的表达低于正常体重者(P<0.05);4组卵泡液脂联素含量明显低于血清含量(P<0.05)且两者显著相关(r=0.38,P<0.01);颗粒细胞内无脂联素mRNA的表达;PCOS患者血清脂联素与BMI负相关(r=-0.394,P<0.05),与注射HCG日>14mm卵泡数正相关(r=0.381,P<0.05);妊娠患者血清脂联素水平明显高于未妊娠者(P<0.05)。结论:人卵巢黄素化颗粒细胞有脂联素受体mRNA的表达,但不表达脂联素mRNA;脂联素及其受体表达与肥胖密切相关,与PCOS无明显相关性;采卵日血清中高水平脂联素可预示良好的IVF结局。