Prolactin and cortisol levels in women with endometriosis.

Endometriosis is a progressive estrogen-dependent disease affecting women during their reproductive years. The objective of the present study was to investigate whether endometriosis is associated with stress parameters. We determined cortisol and prolactin levels in serum, peritoneal and follicular fluid from infertile women with endometriosis and fertile women without the disease. The extent of the disease was staged according to the revised American Fertility Society classification (1997). Serum and peritoneal fluid were collected from 49 women aged 19 to 39 years undergoing laparoscopy. Eighteen women had stage I-II endometriosis and 10 had stage III-IV. Controls were 21 women undergoing laparoscopy for tubal sterilization. Follicular fluid was obtained from 39 women aged 25-39 years undergoing in vitro fertilization (21 infertile women with endometriosis and 18 infertile women without endometriosis). Serum prolactin levels were significantly higher in infertile women with stage III-IV endometriosis (28.9 +/- 2.1 ng/mL) than in healthy controls (13.2 +/- 2.1 ng/mL). Serum cortisol levels were significantly higher in infertile women with stage III-IV endometriosis (20.1 +/- 1.3 ng/mL) than in controls (10.5 +/- 1.4 ng/mL). Cortisol and prolactin levels in follicular fluid and peritoneal fluid did not differ significantly between groups. The high levels of cortisol and prolactin in the serum from women with endometriosis might contribute to the subfertility frequently associated with the disease. Moreover, since higher levels of cortisol and prolactin are often associated with stress, it is probable that stress might contribute to the development of endometriosis and its progression to advanced stages of the disease.

Prolactin and cortisol levels in women with endometriosis

Endometriosis is a progressive estrogen-dependent disease affecting women during their reproductive years. The objective of the present study was to investigate whether endometriosis is associated with stress parameters. We determined cortisol and prolactin levels in serum, peritoneal and follicular fluid from infertile women with endometriosis and fertile women without the disease. The extent of the disease was staged according to the revised American Fertility Society classification (1997). Serum and peritoneal fluid were collected from 49 women aged 19 to 39 years undergoing laparoscopy. Eighteen women had stage I-II endometriosis and 10 had stage III-IV. Controls were 21 women undergoing laparoscopy for tubal sterilization. Follicular fluid was obtained from 39 women aged 25-39 years undergoing in vitro fertilization (21 infertile women with endometriosis and 18 infertile women without endometriosis). Serum prolactin levels were significantly higher in infertile women with stage III-IV endometriosis (28.9 ± 2.1 ng/mL) than in healthy controls (13.2 ± 2.1 ng/mL). Serum cortisol levels were significantly higher in infertile women with stage III-IV endometriosis (20.1 ± 1.3 ng/mL) than in controls (10.5 ± 1.4 ng/mL). Cortisol and prolactin levels in follicular fluid and peritoneal fluid did not differ significantly between groups. The high levels of cortisol and prolactin in the serum from women with endometriosis might contribute to the subfertility frequently associated with the disease. Moreover, since higher levels of cortisol and prolactin are often associated with stress, it is probable that stress might contribute to the development of endometriosis and its progression to advanced stages of the disease.

Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome.

A longitudinal prospective study was conducted in 21 women with polycistic ovary syndrome (PCOS), aged 27.20 +/- 5.02 years and treated with metformin (1500 mg/day)for 8 weeks. The patients were assessed for spontaneous menstruation, weight, body mass index (BMI), waist circumference, waist/hip ratio (WHR), glucose and insulin concentrations under fasting conditions and after a 75-g glucose tolerance test, lipid profile, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF)-I. Spontaneous menstruation was observed in 81% of the women treated with metformin, with no changes in weight or BMI. Waist measurement and the WHR were reduced. The quantitative insulin sensitivity check index (QUICKI) improved from 0.33 +/- 0.03 to 0.35 +/- 0.04 (p < 0.005), and serum total cholesterol and low-density lipoprotein-cholesterol were reduced, while high-density lipoprotein-cholesterol was increased. Serum testosterone concentrations were also reduced. There were no differences in serum triglycerides, SHBG or IGF-I. The occurrence of spontaneous menstruation and changes in the pattern of body fat distribution, the reduction in serum testosterone concentrations, the improvement in lipid profile and the reduction of insulinemia with the use of metformin permit us to conclude that treatment with this drug is of benefit to women with PCOS.

Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes.

The objective of the present study was to examine the association between follicular fluid (FF) steroid concentration and oocyte maturity and fertilization rates. Seventeen infertile patients were submitted to ovulation induction with urinary human follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after hCG administration, the oocytes were analyzed for maturity and 81 of them were incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone, androstenedione, and testosterone were measured in the FF. E2 and testosterone levels were significantly higher in FF containing immature oocytes (median = 618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median = 368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and estrone levels were not significantly different between mature and immature oocytes. The application of the receiver-operating characteristic curve statistical approach to determine the best cut-off point for the discrimination between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0% sensitivity and 81.8% specificity) and of 10.4 ng/ml for testosterone (90.9% sensitivity and 82.4% specificity). Follicular diameter was associated negatively with E2 and testosterone levels in FF. There was a significant increase in progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF containing mature oocytes, suggesting a reduction in conversion of C21 to C19, but not in aromatase activity. The overall fertility rate was 61% but there was no correlation between the steroid levels or their ratios and the fertilization rates. E2 and testosterone levels in FF may be used as a predictive parameter of oocyte maturity, but not for the in vitro fertilization rate.

Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes

The objective of the present study was to examine the association between follicular fluid (FF) steroid concentration and oocyte maturity and fertilization rates. Seventeen infertile patients were submitted to ovulation induction with urinary human follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after hCG administration, the oocytes were analyzed for maturity and 81 of them were incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone, androstenedione, and testosterone were measured in the FF. E2 and testosterone levels were significantly higher in FF containing immature oocytes (median = 618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median = 368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and estrone levels were not significantly different between mature and immature oocytes. The application of the receiver-operating characteristic curve statistical approach to determine the best cut-off point for the discrimination between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0 percent sensitivity and 81.8 percent specificity) and of 10.4 ng/ml for testosterone (90.9 percent sensitivity and 82.4 percent specificity). Follicular diameter was associated negatively with E2 and testosterone levels in FF. There was a significant increase in progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF containing mature oocytes, suggesting a reduction in conversion of C21 to C19, but not in aromatase activity. The overall fertility rate was 61 percent but there was no correlation between the steroid levels or their ratios and the fertilization rates. E2 and testosterone levels in FF may be used as a predictive parameter of oocyte maturity, but not for the in vitro fertilization rate.

Natural product inhibitors of ovarian neoplasia.

The present work constitutes a review of the literature on natural products with potential antitumor activity against ovarian neoplasias. The review refers to five plant extracts and sixty-nine compounds isolated from higher plants and microorganisms, which are classified in appropriate chemical groups and model tested, and cites their activity. Some aspects of recent research with natural products directed to ward producing drugs which are inhibitors of ovarian neoplasia are discussed.

Effect of inseminated volume on intrauterine insemination.

PURPOSE: Intrauterine insemination (IUI) is a method for the treatment of marital infertility involving the intrauterine or fallopian deposition of washed spermatozoa, depending on the amount of inseminated semen. In view of the divergent opinions about the inseminated volume, the objective of this study was to compare the two techniques (3.0 mL or 0.5 mL) in two groups of patients. METHODS: We performed 164 cycles of ovulation induction followed by IUI. The patients were divided into two groups according to the technique used. Group low volume--50 cycles and 0.5 mL of inseminated semen; Group high volume--114 cycles and 3.0 mL of inseminated semen. The cycle was monitored on the basis of endometrial thickness and follicular development measured by transvaginal ultrasound. Human chorionic gonadotrophin (hCG) was administered in the presence of a follicle measuring 18 mm in mean diameter. The procedure was performed after sperm washing using a discontinuous PureSperm gradient, 40 h later. RESULTS: We obtained a similar clinical pregnancy rate for the two groups (14.0% for Group low volume and 15.7% for Group high volume). There was one abortion in each group. We detected no interference by any etiology of infertility or by the total motile recovered sperm with pregnancy rate. CONCLUSIONS: The results did not demonstrate superiority of one method over the other, with both therapeutic alternatives being satisfactory for the treatment of infertile couples.

Effect of transitory hyperprolactinemia on in vitro fertilization of human oocytes.

OBJECTIVE: To examine the changes in plasma prolactin (PRL) during ovarian hyperstimulation (OH) and the influence of hyperprolactinemia on folliculogenesis, oocyte retrieval and in vitro fertilization (IVF) success rates and the usefulness of the metoclopramide (MCP) test in predicting the onset of hyperprolactinemia. STUDY DESIGN: Forty-nine cycles of OH were induced in 32 infertile women using follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (GI) (n = 36), also in association with gonadotropin-releasing hormone (GII) (n = 13). The MCP test (10 mg, intravenously) was performed on fertile control women (control group, n = 9) and in GI (n = 21) and GII (n = 8) patients. RESULTS: Plasma PRL and estradiol levels increased during OH, reaching maximum levels on the day preceding oocyte retrieval in GI and GII. Since these two groups exhibited similar PRL curves, they were evaluated as a single group. Patients showing an increase in PRL of > 200% presented a greater number of follicles with a mean diameter > or = 12 mm and more mature oocytes and better IVF success rates than patients with a PRL increase < or = 200%. Oocyte retrieval did not differ between the groups. The MCP test showed hyperresponsiveness in the three groups studied, but no correlation was found between the PRL increase in this test and that during OH. CONCLUSION: Plasma PRL and estradiol levels increase during OH, while the MCP test cannot predict the onset of hyperprolactinemia. Transitory hyperprolactinemia seems to be associated with an increase in the numbers of follicles with a mean diameter > or = 12 mm and with more mature oocytes and better IVF success rates.

Prenatal diagnosis of fetal ovarian hyperstimulation.

A case of prenatal diagnosis of fetal ovarian hyperstimulation in a pregnancy of 35 weeks is reported. Two large cystic septate ovaries with no internal vegetations were observed in the fetal abdomen. The fetus was macrosomic and the remaining morphology was normal. Polyhydramnios and placental thickening were present, with no other macro- or microscopic alterations. The only significant maternal change detected was elevation of blood beta-human chorionic gonadotropin (beta-hCG) levels. Evaluation of the newborn confirmed the prenatal diagnosis, with progressive and spontaneous regression of fetal ovarian volume and of maternal serum beta-hCG occurring after delivery.

Hypogonadotropic hypogonadism: retrospective analysis of 19 cases.

OBJECTIVES: To survey the clinical data of patients with isolated gonadotropin deficiency. METHODS: We retrospectively surveyed the medical records of 19 patients with isolated gonadotropin deficiency aged 16-31 years (mean: 20 years). The major complaint was primary amenorrhea in 100% of the patients, with 42.1% of them also reporting absence of secondary sex traits, and 10% reporting anosmia or hyposmia. Seventy-four percent of the patients had been submitted to hormonal replacement therapy. RESULTS: Bone densitometry was determined in 5 patients and revealed lumbar spine osteopenia in 3 patients and femoral osteopenia in 1. An association with urologic malformations was detected in 10.5% of cases and an association with gynecologic malformations was detected in 31.6%. CONCLUSIONS: Isolated gonadotropin deficiency can be easily diagnosed but requires early estrogen replacement therapy because of a higher risk of osteopenia and consequently of osteoporosis. Concomitant urogenital malformations are frequent and should be investigated.

Familial risk among patients with endometriosis.

PURPOSE: The objective of the present study was to determine the prevalence of endometriosis among the relatives of patients with confirmed endometriosis. METHODS: We analyzed the prevalence of endometriosis among first-, second-, and third-degree relatives in a group of 101 patients with varying symptoms related to endometriosis seen at two public hospitals and submitted to laparoscopy and/or laparotomy. The control group consisted of 43 women submitted to laparoscopy without a diagnosis of endometriosis. RESULTS: Among the patients with endometriosis, we detected nine families with a positive history of endometriosis, comprising one mother, six sisters, three aunts, and two cousins, as opposed to no case among the controls. CONCLUSIONS: These data confirm a familial tendency for endometriosis and suggest that this disorder has a genetic basis.

Induction of ovulation with clomiphene citrate in combination with metoclopramide in patients with amenorrhea of hypothalamic origin.

Literature data have demonstrated that the chronic use of metoclopramide (MCP), a dopamine antagonist, causes increased gonadotropin secretion in patients with hypothalamic amenorrhea but without triggering ovulation. It has also been observed that women with hypothalamic amenorrhea respond poorly to ovulation induction with clomiphene citrate (CC). On this basis, the objective of the present study was to determine the effect of MCP on the response to CC in patients with hypothalamic amenorrhea in order to evaluate the validity of the simultaneous use of these drugs as ovulation inducers in this type of chronic anovulation. Twenty-two patients with amenorrhea of hypothalamic origin were submitted to a randomized double blind study in which one tablet of 5 mg MCP or placebo was administered every 8 hours for 2 months. After the 30th day of medication (MCP or placebo), CC, 100 mg orally, was additionally administered to both groups for 5 days. Blood samples were collected on days 1, 15 and 30 during the first month of the study and on days 7, 14 and 21 after the last CC tablet during the second month, for later measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol and progesterone by radioimmunoassay. The group that received MCP showed a significant increase in LH and FSH during the first month of the study, as well as a slighter increase in estradiol. Prolactin increased only during the second stage of treatment. No significant increases in gonadotropins, prolactin or estradiol occurred in the placebo group. In the group treated with MCP, 40% of the patients ovulated after CC, with menstruation occurring in 60% of them. In the placebo group, 33.3% of the women ovulated after CC and 44.4% menstruated at the end of the study. We conclude that MCP increases the circulating levels of LH, FSH, estradiol and prolactin in patients with hypothalamic amenorrhea and low estrogen levels, supporting the hypothesis that an increase in hypothalamic dopaminergic tonus occurs in these patients. On the other hand, the combination of MCP and CC does not improve the rate of ovulation compared to placebo.

Insulin secretion in obese and non-obese women with polycystic ovary syndrome and its relationship with hyperandrogenism.

Insulin resistance has been reported to be associated with hyperandrogenism and polycystic ovaries. To study the prevalence of insulin resistance in patients with polycystic ovary syndrome (PCO) and the correlation between hyperinsulinemia and hyperandrogenism, 48 patients were divided into four groups: group 1, non-obese ovulatory women (n = 10); group 2, obese ovulatory women (n = 9); group 3, non-obese women with PCO (n = 14); group 4, obese women with PCO (n = 15). Each patient was submitted to an oral glucose tolerance test (OGTT). Glucose, insulin, androstenedione and testosterone levels were determined and the blood glucose and insulin response of women with PCO and normal women were compared. Glucose intolerance was observed in group 3 (28.6%) and group 4 (40%) but not in groups 1 or 2, and hyperinsulinemia was observed in group 2 (66.7%), group 3 (64.3%) and group 4 (86.6%). There was a correlation between androstenedione and testosterone levels and insulinemia in group 4. There was also a high prevalence of insulin resistance in patients with PCO regardless of obesity, and hyperandrogenism-aggravated insulin resistance.

Cortisol levels alter the response to metoclopramide in patients with hypothalamic amenorrhea.

The reduction in frequency and/or amplitude of gonadotropin-releasing hormone (GnRH) pulses in patients with amenorrhea of hypothalamic origin has been attributed to increased dopamine activity. The objective of the present study was to determine the role of dopamine in the pathogenesis of hypothalamic amenorrhea. Fourteen patients with hypothalamic amenorrhea, nine of whom had psychogenic amenorrhea and five anorexia nervosa, were studied and compared with nine normal women during the early follicular phase. Metoclopramide (10 mg), a dopamine antagonist, was infused intravenously and blood samples were collected at 15-min intervals for 2 h for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) measurement by radioimmunoassay. Both the hypothalamic amenorrhea (psychogenic amenorrhea and anorexia nervosa) and control groups were unresponsive to FSH, suggesting that dopamine may have little or no effect on FSH secretion. Five patients of the psychogenic amenorrhea group responded to LH (responsive psychogenic amenorrhea) and four did not (non-responsive psychogenic amenorrhea). No anorexia nervosa or control patient responded to the stimulus. Responsive psychogenic amenorrhea patients showed decreased basal cortisol levels compared to the non-responsive psychogenic amenorrhea and anorexia nervosa groups. It is possible that patients with exclusive alterations in the dopaminergic system are those who respond to metoclopramide (responsive psychogenic amenorrhea group), whereas patients who also have involvement of the hypothalamic-adrenal axis like the women with anorexia nervosa, are not responsive to metoclopramide and tend to have elevated cortisol levels. The non-responsive psychogenic amenorrhea group, with elevated cortisol levels, probably represents an intermediate step between the responsive psychogenic amenorrhea and anorexia nervosa patients.

Ovulation induction with low doses of "pure" follicle stimulating hormone using a fixed protocol in patients with polycystic ovarian disease.

OBJECTIVE: Use of a low, fixed dose of purified FSH to induce ovulation in polycystic ovarian syndrome. DESIGN: Fixed protocol, using 75 IU/day of "pure" FSH starting on day 1-5 of menses. SETTING: University outpatient clinic. PATIENTS AND INTERVENTIONS: Seventeen patients, aged 18-38, with clomiphene-resistant polycystic ovarian syndrome, for 23 cycles. All received 50 mg medroxyprogesterone to induce menstrual flow. "Pure" FSH given i.m. for eight to ten days. If follicle reached > or = 18 mm, hCG (5,000 IU) was given, in one-half of cases, in a single dose to induce rupture. MAIN OUTCOME MEASURES: Hormonal measurements (plasma LH, FSH, estradiol, testosterone, progesterone); daily, LH/FSH ratio; daily abdominal sonogram. RESULTS: I: No follicular growth (3 cycles; 13%); II: Inadequate follicular growth (< or = 14 mm--6 cycles; 26%); IIIa: Follicle > or = 18 mm, hCG given; 100% ovulatory; IIIb: Follicle > or = 18 mm, no hCG given; 2/7 ovulatory. Hyperstimulation: one (moderate) in IIIa; one (mild) in IIIb. CONCLUSIONS: Fixed protocol of low-dose, "pure" FSH produces good results, especially combined with hCG, which is effective up to 48 hours after last injection of FSH.

Prevalence of anti-cardiolipin antibody in habitual aborters.

An enzyme-linked immunosorbent assay was developed for the detection of anticardiolipin antibody (ACA) in habitual aborters. Results above the 98th percentile of a distribution of 100 blood donors were considered to be positive. Specific binding index for ACA was higher in 20 patients with at least 3 consecutive spontaneous abortions (group A) than in 20 women with at least one live birth without pregnancy wastage (group B). ACA was detected in 4 patients of group A and in none of the women of group B. Most of the pregnancy wastages occurred after the first trimester in ACA-positive patients and during the first trimester in ACA-negative patients.

Effects of clomiphene citrate on pituitary luteinizing hormone and follicle-stimulating hormone release in women before and after treatment with ethinyl estradiol.

OBJECTIVE: To evaluate the effects of clomiphene citrate (CC) on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in hypoestrogenic women and in the same women after treatment with ethinyl estradiol (EE2). DESIGN: The study was of a prospective nature and was conducted on selected patients. SETTING: Volunteer women were studied in a tertiary care public hospital. PATIENTS: The 10 patients studied were selected on the basis of hypogonadal status (menopause, premature ovarian failure, or gonadal dysgenesis and Turner phenotype) and no hormonal treatment. INTERVENTIONS: Gonadotropin-releasing hormone (GnRH) was continually infused at the dose of 0.2 micrograms/min for 4 hours before and after the use of CC and/or EE2. MAIN OUTCOME MEASURE: The study was performed with the objective of determining the effect of estrogen (E) levels on the action of CC on in vivo gonadotropin release. RESULTS: In the presence of hypoestrogenic conditions, CC had no pituitary action. However, after EE2 treatment CC promoted greater FSH release and a significant inhibition of LH release from the pituitary. CONCLUSION: Clomiphene citrate needs a basal E level to be able to act on the pituitary. In normoestrogenic states and under GnRH stimulation, CC preferentially promotes FSH release while presenting a predominantly inhibitory effect on LH release.

Association of microscopic gonadoblastoma and contralateral ovarian fibroadenoma in patients with gonadal dysgenesis and Turner phenotype.

A rare case of microscopic gonadoblastoma associated with gonadal fibroadenoma in a patient with gonadal dysgenesis and Turner phenotype is reported. The higher incidence of tumor pathologies in patients with gonadal dysgenesis presenting a Y chromosome in their karyotype is discussed, and the need for judicious microscopic analysis of the gonadal streaks of these patients for the detection of possible incipient tumors is emphasized.