Color and pulsed Doppler sonography, gray-scale imaging, and serum CA 125 in the assessment of adnexal disease.

OBJECTIVE: To compare color and pulsed Doppler sonography with gray-scale ultrasound imaging and serum CA 125 levels in establishing accurate preoperative diagnoses of adnexal masses. METHODS: Medical records of 109 patients referred with preexisting adnexal lesions were reviewed retrospectively by comparing preoperative ultrasonic data (gray-scale imaging and color and pulsed Doppler findings) with serum CA 125 levels. RESULTS: Eighty-three masses were removed surgically, confirming seven malignancies and 76 benign tumors, and 26 masses were followed; 15 regressed and 11 persisted. Color and pulsed Doppler sonography showed the highest sensitivity, followed by gray-scale imaging, whereas serum CA 125 levels revealed the highest specificity in distinguishing malignant from benign adnexal tumors. All three methods had high negative predictive values (96-100%), whereas only serum CA 125 had a positive predictive value greater than 50%. CONCLUSION: Color and pulsed Doppler sonography, which demonstrate a tumor angiogenic activity, are as accurate as gray-scale imaging in the assessment of adnexal lesions. Together with serum CA 125 marker levels, they produce high negative predictive values, providing reassurance that an adnexal mass is benign.

Transvaginal color Doppler determination of the ovarian and uterine blood flow characteristics in polycystic ovary disease.

OBJECTIVE: To determine blood flow characteristics of ovarian and uterine arteries in patients with endocrinologically and clinically confirmed polycystic ovary disease (PCOD) in comparison with blood flow parameters observed in patients with spontaneous ovulatory cycles. DESIGN: Controlled clinical study. SETTING: Patients from Infertility Service in a tertiary care institution. PATIENTS: Forty patients with confirmed PCOD and 50 control patients in various phases of spontaneous menstrual cycles. MAIN OUTCOME MEASURE: Using transvaginal color Doppler sonography to determine ovarian morphology, ovarian blood vessel visualization rates, and ovarian and uterine arteries blood flow parameters (resistance index, pulsatility index, and maximal peak velocity). These parameters were correlated with serum hormone levels. RESULTS: Polycystic ovaries showed typical vascular pattern: increased stromal vascularity, a positive correlation between increased blood velocities and serum LH levels, and a trend toward lower resistance index and pulsatility index values, whereas uterine arteries revealed significantly increased resistance index and pulsatility index values. CONCLUSIONS: The observed specific intraovarian and uterine vascular pattern in PCOD patients may provide additional data for conventional endocrinologic and ultrasonic diagnostic methods for PCOD.

The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity: a prospective study using transvaginal color Doppler sonography.

The objective of this study was to correlate, during 12 weeks of therapy with gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the hemodynamic changes on the uterine artery and the leiomyometrial supplying vessels. Twenty-three premenopausal women with clinically diagnosed uterine leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma volumes and blood flow characteristics of the main uterine artery and leiomyoma supplying vessels-resistance index (RI), pulsatility index (PI) and peak-systolic velocity, obtained by transvaginal color Doppler sonography-were compared with treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy. The first event in the chronological response to the GnRH-a therapy was a statistically significant increase in RI and PI values for major leiomyoma vessels, observed at the end of the 4th week (p < 0.05), which increased significantly after 8 and 12 weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct correlation with a significant decrease of estradiol levels after 4, 8 and 12 weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease of blood flow in the leiomyometrial vessels was followed by a significant decrease of the main uterine artery blood flow after 8 weeks and uterine and leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy. We concluded that a significant increase in leiomyometrial vessels RI and PI values, which was found 4 weeks after the first dose of GnRH-a, but without major leiomyoma volume decrease, emphasizes that the first significant effect of GnRH therapy in the process of uterine and leiomyoma volume shrinkage is the reduction of leiomyometrial rather than uterine blood flow. This effect is followed by a considerable reduction of uterine vascularity and a significant decrease of uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate therapy duration.

Endovaginal sonography for the early diagnosis of intrauterine and ectopic pregnancies.

Endovaginal sonography, together with beta-HCG titre, was used to diagnose ectopic pregnancy in 58 patients. Transabdominal ultrasound failed to conclude this diagnosis. The data from endovaginal sonography revealed the presence of a gestational sac in all 15 patients with normal pregnancies at a beta-HCG level of 1042 mIU/ml. Of the 23 patients with pathological pregnancies only 61% had an intrauterine gestational sac. Only 15% of the 20 patients with ectopic pregnancies showed an increase in beta-HCG greater than 66% in 48 h, while in normal pregnancy, this increase was found in 71% of the patients. The endovaginal findings of the ectopic gestation revealed a complex adnexal mass in 55%, a cystic mass in 30% and fluid in the cul-de-sac in 20%. The diagnostic indices of adnexal and cul-de-sac sonographic findings in the ectopic group further improved specificity and positive predictive accuracy. The detection of ectopic versus intrauterine gestation showed a high sensitivity of 95%, a specificity of 100%, a positive predictability of 100% and a negative predictability of 97%. The data confirm the value and reliability of endovaginal and cul-de-sac sonography, combined with measurement of the beta-HCG level in the early diagnosis of ectopic pregnancy. This combined approach not only makes the differentiation between normal and extrauterine gestation more accurate but also helps to avoid unnecessary diagnostic laparoscopy and hospitalization.

Bromocriptine in polycystic ovarian disease: a controlled clinical trial.

Bromocriptine and placebo were given to a group of 20 polycystic ovarian disease patients on a double-blind, cross-over basis. Patients were studied for three cycles: a baseline cycle without any medication, a placebo-treated cycle, and a bromocriptine-treated cycle with multiple plasma samples taken during the different phases of the menstrual cycle. The clinical response to bromocriptine was compared with that of a placebo for the following hormones: prolactin (PRL), luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, androstenedione, estradiol-17 beta (E2), estrone (E1), and progesterone. Patients were divided into two subgroups: hyperprolactinemic (basal PRL greater than 20 ng/mL) and normoprolactinemic (basal PRL less than 20 ng/mL), and the response of both subgroups to bromocriptine was compared. Prolactin, LH/FSH ratio, testosterone, and E1 showed a significant drop with bromocriptine, whereas E2 significantly increased. Two out of nine amenorrheic polycystic ovarian disease patients menstruated during bromocriptine treatment, and three patients showed evidence of ovulation.

Ovarian follicular fluid beta-endorphin levels in normal and polycystic ovaries.

The possibility of local ovarian production of beta-endorphin prompted us to measure beta-endorphin levels in 19 follicular fluid samples obtained from normal ovaries and compare them with beta-endorphin plasma levels in 19 women with normal ovulation. beta-Endorphin was extracted through Sepharose-treated chromatography columns and assayed with a specific anti-beta-endorphin antibody. Follicular fluid beta-endorphin levels (21.3 +/- 10.8 pg/ml) were significantly higher (p less than 0.01) than the plasma levels (15.5 +/- 3.35 pg/ml). There was no significant correlation between plasma and follicular fluid beta-endorphin concentrations. Follicles greater than 1 cm in size contained more beta-endorphin than follicles less than 1 cm in size (22.7 +/- 3.5 versus 18.7 +/- 4.4 pg/ml, p less than 0.05). Five follicular fluid samples were obtained from polycystic ovaries. The mean beta-endorphin content (45.1 +/- 7.7 pg/ml) in these follicles was significantly higher than that of normal ovaries (p = 0.001). It is concluded that the ovaries produce beta-endorphin and that polycystic ovaries produce more beta-endorphin than normal ovaries.

A controlled clinical trial for the effect of bromocriptine on the adrenal contribution in polycystic ovarian disease.

Adrenal involvement in polycystic ovarian disease was assessed by measuring dehydroepiandrosterone sulphate in 20 polycystic ovarian disease patients. The response of dehydroepiandrosterone sulphate to bromocriptine treatment was compared to that of placebo, both being given for one cycle on a double-blind, cross over basis. The mean basal DHEA-S was above the upper limit of the normal range (6793 nmol/l) in three patients. The mean basal dehydroepiandrosterone sulphate in the polycystic ovarian disease group was significantly higher than the mean of the normal control group (P less than 0.01). Dehydroepiandrosterone sulphate showed a significant drop with bromocriptine as compared to placebo (P less than 0.001) and a significant correlation with prolactin both before (P less than 0.001) and after treatment with bromocriptine (P less than 0.001). These findings support the hypothesis of adrenal involvement in polycystic ovarian disease and prove the significant effect of bromocriptine on the adrenal which might be of therapeutic value.

Immunoreactive beta-endorphin in human ovaries.

Beta-endorphin (beta-EP) immunostainable cells were demonstrated in human ovarian tissue using a non-cross-reacting anti-beta-EP serum and the avidin-biotin-peroxidase detection technique. In ovaries from ovulating and premenopausal women, beta-EP immunoreactivity was localized in the luteinized cells of theca interna of maturing follicles with almost negligible staining in granulosa cells; cells of primary follicles did not stain. In corpora lutea, luteinized cells in both theca interna and granulosa, layers were equally positive. In postmenopausal ovaries, staining was detectable only in scattered luteinized stromal cells. This is the first report on the presence of immunoreactive beta-EP in human ovaries, in which beta-EP seems to be produced by the same sex cord cells engaged in active steroidogenesis and may be under gonadotropin central regulation. The significance of this finding is discussed.

Correlation of the ultrasonic appearance of the ovaries in polycystic ovarian disease and the clinical, hormonal, and laparoscopic findings.

The ovarian ultrasonic appearance in 20 patients with polycystic ovarian disease was studied and correlated to the clinical, hormonal, and laparoscopic findings. Ultrasound studies showed that both ovaries were enlarged in 15 patients (15.46 +/- 2.5 cm3). Maximum ovarian surface area was 9.75 +/- 3.38 cm2. Three ultrasonic patterns were detected: (1) isoechoic, with no discernible cysts (four patients); (2) hypoechoic, with multiple small cysts of less than 1 cm (11 patients); (3) hypoechoic, with single cyst of greater than 1 cm (five patients). Ultrasonic estimation of ovarian size was superior to clinical assessment and equal to that of laparoscopic examination. Subtle differences existed between the ultrasonic appearance of the ovaries in hyperprolactinemic subgroups of polycystic ovarian disease compared to normoprolactinemic ones. However, no significant relationship was found between the ovarian size and any of the hormones studied. Obesity, amenorrhea, hirsutism, hyperprolactinemia, and elevated testosterone and dehydroepiandrosterone sulfate levels were more common in the group with enlarged ovaries, whereas oligomenorrhea, elevated luteinizing hormone/follicle-stimulating hormone ratio, and elevated androstenedione and estrone levels occurred more frequently in the group with normal-sized ovaries. The value of ultrasound studies in the management of polycystic ovarian disease is emphasized.

Menopausal syndrome: plasma levels of beta-endorphin in post-menopausal women measured by a specific radioimmunoassay.

beta-Endorphin (beta-EP) levels were measured in 13 post-menopausal women (7 surgical, 6 physiological) using a new highly specific and accurate radioimmunoassay, and were found to be significantly lower than among 10 normally menstruating controls (48.6 +/- 13.8 pg/ml vs. 70.0 +/- 18 pg/ml, P less than 0.005). beta-EP levels were measured prior to and 5 days after surgery in 3 of the oophorectomized women, and were found to have decreased by an average of 41%. beta-EP levels were measured immediately after hot flashes experienced by 4 of the post-menopausal women during regular clinic visits, and were found to be significantly elevated above baseline levels (P less than 0.02). Our data confirmed the findings of Genazzani et al. [10], a significant lowering of beta-EP at menopause. Also, the data from the small number of beta-EP plasma levels we studied during hot flashes, suggests a possible role of beta-EP either directly or indirectly on the genesis of hot flashes.

Elevated plasma levels of beta-endorphin in a group of women with polycystic ovarian disease.

The relationship of endogenous opiates in patients with polycystic ovarian disease (PCOD) and their influence on body weight was studied. The study group consisted of 19 women with PCOD. They were amenorrheic, hirsute, and hyperandrogenic, and their average weight was 124% of the ideal body weight. They had luteinizing hormone/follicle-stimulating hormone ratios greater than or equal to 2. The control group consisted of ten women with regular ovulatory menses. Plasma beta-endorphin (beta-EP) was measured by using a very specific radioimmunoassay. beta-Lipotropin (beta-LPH) was entirely removed from the sample by preincubation of the plasma with rabbit anti-beta-LPH/Sepharose complex (Pharmacia, New Brunswick, NJ). The mean +/- standard deviation of the plasma beta-EP in the control group was 70.18 +/- 18.06 pg/ml, and the mean +/- standard deviation of beta-EP in the study group was 185.6 +/- 93.4 pg/ml, which was significantly higher than the control levels (P less than 0.001). A significant correlation was also found between plasma beta-EP level and the patient's weight in the PCOD group (r = 0.462, P = 0.025). The data from this study suggest that the elevated levels of endogenous opiates may be involved in the pathophysiology of PCOD and be related to inappropriate secretion of gonadotropins influencing body weight.

Familial 46,XX gonadal dysgenesis.

Two sisters, ages 16 and 17, presented with secondary amenorrhea. In addition, primary ovarian failure, gonadal dysgenesis, and normal karyotypes were demonstrated. The most significant finding was a history of mumps, which they caught at the same time, 10 years before the onset of the amenorrhea. This disorder suggests that etiologic and environmental factors could prevail either in utero or during childhood. These patients are presented to emphasize the importance of considering gonadal dysgenesis as a differential diagnosis in patients with secondary amenorrhea, especially when the menstrual life has been a short one.

Primary ovarian pregnancy and the intrauterine contraceptive device.

A case of true primary ovarian pregnancy with a Cu-7 intrauterine contraceptive device (IUCD) in situ was studied. All of Spiegelberg's criteria were satisfied. Review of the literature revealed an apparent increase in the frequency of ovarian pregnancy associated with the use of IUCDs.

PIP: A case report of a true ovarian pregnancy with a copper 7 IUD in situ is presented. The histological diagnosis is explained and microscopic photographs presented. A review of the literature reveals that the risk that a pregnancy occurring with an IUD in situ will be ectopic is highly elevated above the normal. The fact is probably due to the mechanism of action of the IUD, i.e., local enzyme or chemical action on the endometrial cavity and Fallopian tubes. Diagnosis in these cases is of particular importance since the presenting symptoms of ectopic pregnancy are often attributed to the IUD itself initially.

Hilar cell tumor of the ovary: preoperative localization by selective retrograde venous sampling.

A well-documented case of hilar cell tumor of the right ovary in a postmenopausal patient is described. Pre-operative retrograde venous catheterization and sampling were used to localize this virilizing tumor.

The reversible behavior of locally invasive endometrial carcinoma in a chromosomally mosaic (45,X/46,Xr(X)) young woman treated with Clomid.

A 22 year-old phenotypic female with a 45,x/46,x, r(x) mosaic complement had anovulatory cycles, histologically normal ovaries, and atypical endometrial hyperplasia which, when clinically followed by repeated biopsies, was found to progress to locally invasive endometrial carcinoma. This was successfully managed by the induction of ovulation with Clomid, which resulted in conversion of the endometrium to a normal secretory pattern for two subsequent years.

Plasma estrogen in patients with endometrial hyperplasia and carcinoma.

In a total of 53 patients, most of whom were over 40 years of age and who presented symptoms of vaginal bleeding, total plasma estrogens were measured with gas liquid chromatography, and the clinical correlates were studied. The results revealed that total plasma estrogen levels in the endometrial hyperplasia and endometrial carcinoma groups were significantly higher than those measured in the control group. In addition, a positive, significant correlation was found between the plasma estrogen levels and obesity in the patients with endometrial carcinoma. The study provides objective data that document the clinical impressions that hyperestrogenism and obesity are significant findings in endometrial carcinoma.

The effect of prostaglandin F2alpha on the placental progesterone level in midtrimester abortion.

A gas chromatograph method has been used for the determination of placental progesterone levels in 14 patients aborted at midtrimester by intra-amniotic instillation of prostaglandin F1alpha, also from a control group (five patients) aborted surgically by dilatation and suction. The results showed that the mean %/- S.E. of placental progesterone in the prostaglandin group was 1.45 mug +/- 0.09 per 1 Gm. of placental tissue, whereas the mean +/- S.E. of the placental progesterone in the surgically aborted group was 5.22 +/- 0.31 mug per 1 Gm. of placental tissue. The difference between the two groups was significant: P EQUALS 0.0001. This low level of placental progesterone in the prostaglandin abortion group could explain the sharp decline of the progesterone levels in the peripheral blood during abortion by intra-amniotic instillation of prostaglandin F2alpha, as observed by our group1, 2 and others.3(-5)

PIP: A gas chromatograph method has been used for the determination of placental progesterone levels in 14 patients aborted at midtrimester by intraamniotic instillation of (PGF) prostaglandin F2alpha and also from a control group (5 patients) aborted surgically by dilatation and suction. The results showed that the mean + or - S.E. of placental progesterone in the PG group was 1.45 mcg + or - 0.09/1 gm of placental tissue, whereas the mean + or - S.E. of the placental progesterone in the surgically aborted group was 5.22 + or - 0.31 mcg/1 gm of placental tissue. The difference between the 2 groups was significant: P=0.0001. This low level of placental progesterone in the PG abortion group could explain the sharp decline of the progesterone levels in the peripheral blood during abortion by intraamniotic instillation of PGF2alpha.

Midtrimester pregnancy interruption and the placental progesterone levels.

Placental progesterone contents were studied in 10 patients therapeutically aborted at midtrimester by intraamniotic infusions of hypertonic saline, and from 14 patients (12-20 weeks) aborted by intraamniotic instillation of prostaglandin F-2alpha. The mean S.E. of the progesterone was 1.99 plus or minus 0.07 ug/g. placental tissue in the first group, while with prostaglandin abortion the placental progesterone was 1.45 plus or minus 0.08 ug/g. tissue, which is significantly lower than the results in the first group (P equals 0.001). The possible mechanism of action of prostaglandin as an effective abortifacient is discussed.

PIP: Placental progesterone (P) levels in patients aborted at midtrimester by intraamniotic instillation of prostaglandin (PG) F2 alpha and by hypertonic saline were compared and correlated to abortion-instillation intervals. 10 patients were instilled with hypertonic saline at midtrimester and 14 patients (12-20 weeks) were instilled with hypertonic saline. PGF2 alpha group average abortion interval was 16.5 + or - 2.1 hours, and the abortion time for saline was 36 + or - 3.4 hours. Placental P levels in the 14 patients aborted with PGF2 alpha ranged from .65 to 1.9 mcg/gm and the mean standard error was 1.45 + or - .09, which was significantly lower (P=.001) than the mean standard error of 1.99 + or - .07 mcg/gm of tissue for hypertonic saline infusion. 2 mechanisms of PGF2 alpha abortifacient effect are theorized: 1) PG may directly interfere with functional integrity of placenta and interrupt P synthesis, or 2) the higher uterine activity associated with PG may impair placenta function by an ischemic insult.