Comparison of mass spectrometry and radioimmunoassay to measure medroxyprogesterone acetate in patients with endometrial cancer.

Serum medroxyprogesterone acetate (MPA) was measured by radioimmunoassay (RIA) and gas chromatography-mass spectrometry (GC-MS) in patients with endometrial cancer. Samples were obtained 3, 6 and 24 h after the oral administration of 100 or 200 mg MPA once a day. The levels obtained by GC-MS were lower (median 16-29%) than those obtained by RIA, which is probably attributable to the presence of metabolites interfering with the RIA. Two commercial MPA formulations gave different MPA serum levels by both RIA and GC-MS. The levels obtained by GC-MS were so low that frequently only partial saturation of the endometrial progesterone receptor may be achieved which may explain why high oral doses are needed to produce optimum therapeutic response.

Suspected ectopic pregnancy: ultrasound findings and hCG levels assessed by an immunofluorometric assay.

One hundred suspected ectopic pregnancies were assessed by ultrasound on the basis of the following criteria: (A) viable intrauterine fetus, intrauterine pregnancy is certain; (B) intrauterine double sac or eccentric ring, intrauterine pregnancy is probable; (C) empty uterus or central ring but no adnexal mass or cul-de-sac fluid, ectopic pregnancy is possible; (D) empty uterus or central ring and an adnexal mass or cul-de-sac fluid, ectopic pregnancy is probable; (E) viable ectopic fetus, ectopic pregnancy is certain. Serum human chorionic gonadotrophin (S-hCG) was detected by an immunofluorometric assay (sensitivity 0.2 i.u./l, cut-off level 10 i.u./l). All the 51 patients in groups A and B had an intrauterine pregnancy. Normal gestational sacs were found also at S-hCG levels of less than 3600 i.u./l, the lowest level being 894 i.u./l. Ectopic pregnancy was confirmed in 29 of the 30 women in groups D and E. In the 19 women categorized into group C serial hCG assay and repeated sonography diagnosed ectopic pregnancy in 12 and miscarriage of an intrauterine pregnancy in the other seven. Ectopic pregnancy was always found when no gestational sac was seen by sonography and the hCG level was greater than 1000 i.u./l.

Serum sex hormone levels in adolescent girls with polymenorrhoea.

The hormone levels of 13 polymenorrhoeic adolescent girls were evaluated. Twenty-eight adolescent girls with regular menstruation served as controls. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, oestradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulphate, and sex hormone binding-globulin were determined in blood samples obtained over one menstrual cycle. In girls with polymenorrhoea the frequency of ovulation was significantly lower than in the control group as estimated on the basis of the progesterone level five days before the onset of menstruation. Low progesterone and oestradiol levels during the late part of the cycle were the main abnormalities of polymenorrhoeic adolescent girls. No differences in the other hormonal parameters were found. The duration of menstrual bleeding was similar in both groups.

The effect of oral contraceptives on hormone profiles of oligomenorrheic adolescent cycles.

Nineteen adolescent girls with oligomenorrhea were studied to evaluate the effect of oral contraceptives (OCs) on hormone profiles, and 19 adolescent girls with regular menstruations served as control subjects. Serum levels of luteinizing hormone and androgens were higher in the oligomenorrheic girls than in the regularly menstruating girls. During the OC treatment the hormone levels of the oligomenorrheic girls decreased, approaching those of the control subjects. During follow-up cycle immediately after stopping the OCs the hormone levels increased rapidly, but in the oligomenorrheic girls the levels of luteinizing hormone, androstenedione, total and free testosterone were still significantly lower at the end of the post-treatment cycle than during the luteal phase of the pre-treatment cycle. The frequency of ovulation decreased to the same magnitude as reported in adults after discontinuation of OCs. No post-pill amenorrhea existed in either group of adolescents.

Endocrinologic features of oligomenorrheic adolescent girls.

The plasma concentrations of sex hormones were measured in 45 oligomenorrheic and 28 regularly menstruating adolescent girls. Testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin levels were determined in blood samples collected during one menstrual cycle. The oligomenorrheic girls had significantly higher concentrations of luteinizing hormone, androstenedione, dehydroepiandrosterone-sulfate, and free testosterone than regularly menstruating girls. Sex hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. The oligomenorrheic girls were not obese. Signs of acne or hirsutism were absent or mild. Sixty-six percent of the oligomenorrheic cycles were ovulatory. The significance of the hormonal findings is discussed.

Ovarian function during oestrogen-progestin replacement treatment in pre-menopausal women.

Thirty-five pre-menopausal women were treated for 3 mth with sequential combinations containing oestradiol valerate and levonorgestrel in two different doses. Three treatment cycles, and 2 cycles before and 2 after treatment were studied. Subjective symptoms were relieved in 62% of women during treatment. Normal secretory phase was observed in 25-53% before and 33-35% at the end of treatment. Serum FSH and the frequency of serum progesterone increase greater than 5 nmol/1 decreased, particularly during treatment with the higher dosage. Ovulations occurred during both treatments; these combinations cannot therefore be used for contraceptive purposes. In ultrasonic studies, the average volume of ovaries in which no follicles were found, was 7.6 cm3. The volume of ovaries with follicles was 10.5 cm3. The follicular growth was often defective, also in ovulatory cycles, in both treatment and control cycles. In ovulatory cycles, luteinized unruptured follicles occurred in 2% before treatment and in 5% during treatment. In anovulatory cycles, persistent follicles were observed in 13% before treatment and in 19% during treatment. The frequency of luteinized unruptured follicle (LUF) syndrome did not increase significantly in pre-menopausal women during oestrogen-progestin treatment. However, persistent follicles were frequent during anovulatory cycles. Serum oestradiol concentrations correlated significantly with the diameter of the dominant follicle. No significant changes were found in uterine volume. Both of the tested regimens are useful for treatment of pre-menopausal symptoms.

Sarcomas of the uterus: a clinicopathologic study of 119 patients.

This series consists of 119 uterine sarcoma patients treated at the University of Helsinki Central Hospital during the 20-year period of 1958 to 1977. It comprises the three main histologic varieties: leiomyosarcomas, 51 patients; mixed müllerian sarcomas, 45 patients; and endometrial stromal sarcomas, 23 patients. The clinicopathological features that could have had a bearing on prognosis were examined retrospectively. The clinical stage at the time of primary treatment was the main prognostic factor. Other important factors were the degree of histologic differentiation and the mitotic activity. The overall five-year survival rate for patients with leiomyosarcomas was 39%; for mixed müllerian sarcomas, 33%; and for endometrial stromal sarcomas, 61%. The ten-year survival figures were 27, 14, and 37%, respectively. Some features of the diagnosis, the natural history, and the different methods of treatment of these diseases are discussed.

Changing pattern of cervical carcinoma: a report of 709 cases of invasive carcinoma treated in 1970-1974.

Seven hundred and nine new cases of carcinoma of the uterine cervix were treated by surgery, radiotherapy, or both at Helsinki University Central Hospital between 1970 and 1974. Of these, 241 (34.0%) died of the disease during the 5-year follow-up period. Three hundred and eighty-three (53.9%) of the patients were operated on and in 112 (29.3%) of them the stage of the disease had been underestimated preoperatively. This was mainly due to the undetected lymph node involvement observed first at operation in 72 cases (18.8%). In 237 of the patients carcinoma was confined to the cervix according to findings at operation but in 24 (10.1%) of them a relapse or metastasis was observed within 5 years. Comparison of the results for 1970-1974 with those from the same hospital for 1926-1969 revealed a reversal in the steady improvement in the total 5-year survival rates. It is concluded that, even if the incidence of cervical carcinoma in Finland is to decrease, the prognosis for the disease may become poorer. This is mainly due to a shift in the peak incidence of cervical carcinoma to older age groups. Also a mass screening program is likely to decrease the relative number of slowly growing, less aggressive type of the disease.

The in vitro fertilization program in Helsinki.

In the in vitro fertilization program at Departments I and II of Gynecology and Obstetrics, University of Helsinki, 57 patients were stimulated with clomiphene and hMG. Follicular growth was monitored by ultrasound and serum estradiol measurements. Laparoscopic follicular puncture was performed 36h after hCG injection. Three hundred seventy-five follicles were punctured and 227 oocytes recovered, representing an oocyte recovery rate of 61%. A total of 130 oocytes (57%) showed evidence of fertilization and 71% of the fertilized oocytes cleaved. Fifty-seven embryo transfers were carried out at the two- to eight-cell stage. Multiple embryos were transferred to 24 patients. Biochemical pregnancies were encountered in two cases; early abortions, 3-5 weeks after implantation, in two cases. One normal ongoing single pregnancy occurred from a transfer of three four-cell embryos.

Estradiol and progesterone receptors in two cases of endometrial stromal sarcoma.

The presence of estradiol and progesterone receptors in endometrial stromal sarcoma (ESS) has not been studied previously. Two cases of ESS are reported in which high concentrations of these receptors were found in the tumor tissue. One of these patients had retained the reactivity to hormone treatment for several years. It is suggested that the steroid receptors should be analyzed in all cases of ESS to find tumors with a high receptor content. Hormone treatment of these patients should be part of the primary adjuvant therapy. In cases of a good response the therapy should be prolonged and continued for the rest of the patient's life.

Sex hormone profiles in oligomenorrheic adolescent girls and the effect of oral contraceptives.

The hormonal profiles and the effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studied. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex-hormone-binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after discontinuation of OC use. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex-hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. Both in oligomenorrheic and regularly menstruating girls OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2 to 4 weeks after treatment the oligomenorrheic girls had significantly lower levels of androstenedione, total and free testosterone, and luteinizing hormone than before treatment. In the control group there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.

PIP: The hormonal profiles and effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studies. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle stimulating hormone, prolactin, and sex hormone binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after OC discontinuation. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex hormone binding globulin concentrations were significantly lower in the oligomenorrheic group. Both inoligomenorrheic and regularly menstruating girls, OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2-4 weeks after treatment, the oligomenorrheic girls had significantly lower levels of androstenedion, total and free testosterone, and luteinizing hormone than before treatment. In the control group, there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.

Modification of aspects of the endocrine response to tracheal intubation by lignocaine, halothane and thiopentone.

The effects of two different concentrations of halothane (0.5 or 1.5%) and two different doses of thiopentone (4.5 or 10 mg kg-1) on the plasma concentrations of cortisol, growth hormone (GH) and prolactin (PRL) were studied in response to the stress of tracheal intubation. Additionally, the effect of the intratracheal administration of 4% lignocaine spray 2 ml was investigated. The study group included 48 healthy women. During a "light" level of halothane and thiopentone anaesthesia, the plasma concentration of cortisol increased in response to tracheal intubation in the patients who did not receive intratracheal analgesia. Topical analgesia with lignocaine prevented the increase in cortisol concentration and this would seem to indicate that the increase was caused by the stress of laryngoscopy and intubation. At a deeper level of halothane anaesthesia, and in association with the larger dose of thiopentone the increase in cortisol concentration was suppressed. GH did not change from the preanaesthetic value in any group and there were no differences between the control group and the study groups. PRL increased significantly in all groups. Increasing the dose of thiopentone caused a further increase in PRL concentration which indicated a direct stimulatory action of thiopentone on PRL release.

Effect of intratracheal lignocaine, halothane and thiopentone on changes in plasma beta-endorphin immunoreactivity in response to tracheal intubation.

Alterations in the concentration of plasma beta-endorphin immunoreactivity (beta-EPir), in response to the stress of tracheal intubation, were measured in 48 women during halothane anaesthesia. The increase in plasma beta-EPir in response to tracheal intubation could be prevented by topical analgesia (4% lignocaine 2 ml) to the trachea, a deeper level of halothane anaesthesia (1.5%) and an increased dose of thiopentone (10 mg kg-1). It was concluded that a low plasma beta-EPir value is a sign of stress-free anaesthesia and that measurements of plasma beta-EPir may be useful in determining the degree of stress present during various anaesthetic procedures.

Estradiol and progesterone receptors in gynecologic sarcomas.

We report the concentrations of estradiol and progesterone receptors found in the tumor tissue of 5 patients with leiomyosarcoma, 4 of uterine and one of ventricular origin, and of 5 patients with uterine or ovarian carcinosarcoma. Steroid receptor positive and negative tumors were present in both groups of sarcoma. One uterine leiomyosarcoma had a high concentration of estradiol and progesterone receptors, 37 fmoles/mg protein and 156 fmoles/mg protein, respectively. We suggest that steroid receptors should be analysed in all gynecologic sarcomas.

Treatment of vaginal endometriosis with danazol.

Six infertile patients with vaginal endometriosis were treated with danazol at 600 mg daily for 6 months. Three patients had previously undergone surgery for pelvic endometriosis. After 4 months of danazol treatment there was a clear reduction in the size and number of the lesions in all the patients. At the end of the treatment 4 patients still had small lesions, which showed histological evidence of regressive changes. Four women became pregnant within 6 months of the termination of therapy.

Fertility prognosis after surgical treatment of pelvic endometriosis.

A total of 129 infertile patients with endometriosis were treated by surgery. The severity of endometriosis was estimated according to Acosta's classification. The mean pregnancy rate was 51.2%. The pregnancy rate of the patients with primary infertility was 48.9% and, for the secondary infertility group, 56.8%. Two-thirds of the women who became pregnant conceived within one year. The pregnancy outcome in mild endometriosis was 59.1%, in moderate 56.4% and in severe 40%. Eighteen male partners had deficient sperm in the group of 63 women who did not conceive within the follow-up period. In addition to the extent of the disease, factors such as duration of infertility prior to surgery and age at the time of surgery seemed to be important in the fertility prognosis.

Bacterial cultures from intrauterine devices removed from patients with pelvic inflammatory disease.

Bacterial cultures were obtained from intrauterine devices (IUD) removed from 274 patients admitted to the Department of Obstetrics and Gynecology of the University Central Hospital of Helsinki because of suspected pelvic inflammatory disease (PID), meno-metrorrhagia, pain or other conditions potentially caused by an IUD. A diagnosis of serious PID was made in 42 patients, mild PID in 119 patients, while 113 were found to have no infection. An association between positive cultures of beta-hemolytic streptococci and Escherichia coli and PID was found. Positive cultures of Neisseria gonorrhoeae were significantly correlated with PID. The risk of developing PID was significantly greater during the first month after insertion of the IUD than when more than 30 days had elapsed from insertion of the IUD. The significance of the microbes cultured from removal IUDs as causal agents of pelvic inflammatory disease is discussed.