Search PubMed⌕ Search

Biomedical subjects

A Kauppila

Publications and source records attributed to A Kauppila.

At least 109 records · Page 6Linked to original sources

Tamoxifen and natural progesterone as supplements to low-dose postmenopausal estrogen therapy.

Postmenopausal women received 1 mg estrone sulfate a day for 3 weeks in 12 sequences separated by a 7-day interval without medication and every second time by a 10-day treatment with natural progesterone, 100 mg 2 times daily (n = 16), or tamoxifen, 10 mg 2 times daily (n = 17). Both treatments alleviated climacteric symptoms, maturated the vaginal epithelium, and decreased follicle-stimulating hormone, luteinizing hormone, and prolactin concentrations while lipid metabolism remained unaltered. In the estrogen-progesterone group 4 women (25%) were persistently amenorrheic, 12 (75%) experienced 1-5 bleedings per year, and 4 women had proliferative endometrium after treatments. In the estrogen-tamoxifen group 11 women (65%) were amenorrheic, 6 (35%) had 1-4 bleedings per year, and 5 had proliferative endometrium. With the present treatment schedules, tamoxifen was more effective than natural progesterone in inhibiting estrogen stimulation of postmenopausal endometrium.

Alanine Transaminase↗

Hormonal and clinical effects of ketoconazole in hirsute women.

The effects of ketoconazole on pituitary-ovarian function and adrenal function were evaluated in nine hirsute women treated with 400-1200 mg/day for 1-6 months. High dose (800-1200 mg/day) ketoconazole treatment decreased serum androstenedione, dehydroepiandrosterone, and testosterone (T) concentrations, while that of 17 alpha-hydroxyprogesterone increased, suggesting a steroidogenic block at the level of 17,20-desmolase. The decreased serum T and increased sex hormone-binding globulin concentrations led to a significant decrease in the free androgen index. Serum estradiol, cortisol, and dehydroepiandrosterone sulfate concentrations did not change. The serum LH concentration and the LH to FSH ratio increased during treatment, suggesting a negative feedback effect of T on pituitary LH secretion. The hormonal changes that occurred during high dose ketoconazole therapy persisted during subsequent low dose (400 mg/day) treatment. The therapeutic effect of ketoconazole on hirsutism manifested itself at 6 months. We conclude that ketoconazole reduces excessive androgen production in a dose-dependent manner and decreases the free androgen index in hirsute women; these changes are accompanied by significant alleviation of hirsutism.

Adult↗

Effect of clomiphene citrate on prolactin and gonadotropin release during GnRH-analog treatment.

The capacity of the anterior pituitary to secrete prolactin (PRL) and gonadotropins was evaluated by TRH and GnRH stimulation, followed by metoclopramide (MC) administration 1 hour later, before and after clomiphene citrate (CC) priming in 8 endometriosis patients receiving GnRH agonist analog (Buserelin) therapy for 6 months. GnRH-analog treatment lowered the maximal PRL responses to TRH and MC stimulation in the luteal phase, compared to those of 8 normally menstruating control patients. The LH response to GnRH stimulation was also diminished, indicating pituitary desensitization, while the FSH response remained unchanged. Antiestrogen administration during GnRH-analog treatment further reduced the capacity of pituitary lactotropes to secrete PRL in TRH and MC tests, and it increased the LH response but not the FSH response to GnRH stimulation. These data suggest that CC affects the mechanisms controlling PRL and gonadotropin secretions in hypoestrogenic women after prolonged GnRH agonist analog treatment by different modes of action, the action on gonadotropes being stimulatory and that on lactotropes inhibitory.

Adult↗

Hypoprolactinemia and ovarian function.

Thirty-two patients with ovarian hyperstimulation were randomized to receive bromocriptine or placebo from cycle day 5 onward. Bromocriptine decreased serum and follicular fluid prolactin (PRL), accelerated ovarian follicle growth, increased serum and follicular fluid estradiol, lowered luteal phase progesterone, and shortened the luteal phase length of the cycle. The maximal luteal phase estradiol and progesterone concentrations correlated with each other in the placebo group, but not in the bromocriptine group. These findings indicate that hypoprolactinemia interferes with ovarian function. The unchanged concentrations of gonadotropic hormones and pattern of luteinizing hormone pulsation during bromocriptine suggest direct ovarian effects of hypoprolactinemia. Because PRL suppression enhanced follicular responses and inhibited corpus luteum formation and function, the follicular and corpus luteum actions of PRL may be different.

Adult↗

Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy.

Serum selenium concentrations were found to be significantly lower in women with intrahepatic cholestasis of pregnancy than in women with normal pregnancies during the last trimester of pregnancy and post partum. The activity of the selenoenzyme glutathione peroxidase had a significant positive correlation with selenium concentration and it was also significantly lower in women with the disease. These findings suggest that selenium deficiency and reduced glutathione peroxidase activity are associated with the aetiopathogenesis of intrahepatic cholestasis of pregnancy.

Adult↗

Anterior pituitary dysfunction during the luteal phase following ovarian hyperstimulation.

The capacity of the pituitary to secrete prolactin (PRL) and gonadotropins was investigated during the luteal phase of eight normally menstruating tubal infertility patients after ovarian stimulation with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin. The baseline values of PRL were significantly higher (P less than 0.025), those of luteinizing hormone unchanged, and those of follicle-stimulating hormone lower (P less than 0.025) during the treatment than in the control cycles. The maximal response of PRL to the dopamine antagonist metoclopramide was increased (P less than 0.01), whereas the maximal responses of luteinizing hormone (P less than 0.025) and follicle-stimulating hormone (P less than 0.001) to gonadotropin-releasing hormone were lowered in the treatment cycles. The current results indicate that ovarian hyperstimulation with clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin may induce luteal phase pituitary dysfunction, which may affect the luteal phase functions of the corpus luteum.

Adult↗

Micronized oral progesterone increases the circulating level of endometrial secretory PP14/beta-lactoglobulin homologue.

The effect of luteal phase supplementation of micronized oral progesterone, 200 mg daily, on the serum levels of endometrial secretory placental protein 14 (PP14)/beta-lactoglobulin homologue was studied in a double blind/cross-over fashion on five infertile women with apparently normal ovulatory cycles. Blood samples were taken on cycle days 10-12, 20-22 and 24-27, and the serum progesterone and PP14 concentrations were measured by specific radioimmunoassays. In each progesterone cycle the serum progesterone levels were higher than in the corresponding placebo cycle. In each case, the serum concentration of endometrial PP14 was also higher during progesterone than placebo treatment, but this was seen in the late luteal phase only. In view of the previous demonstration of endometrial synthesis of PP14 and the immunological identity between PP14 and progestogen-dependent endometrial protein, these results indicate that endometrial protein secretion can be increased by micronized oral progesterone in infertile ovulatory women whose serum progesterone level is within the normal range.

Administration, Oral↗

Metoclopramide-induced hyperprolactinaemia: effects on corpus luteum function, endometrial steroid receptor concentrations and 17 beta-hydroxysteroid dehydrogenase activity.

Induced hyperprolactinaemia impairs ovarian follicular development, especially during the recruitment period. The consequences of hyperprolactinaemia during the luteal phase alone on corpus luteum function have not been characterized, nor have the actions of excessive circulating PRL on the endometrium. In this study, postovulatory 5-d administration of metoclopramide (MC) increased serum concentrations of PRL and decreased those of pregnenolone and progesterone indicating inhibition of steroidogenesis in the corpus luteum. This effect may partly explain the relatively common failure of implantation in association with induced ovulation using regimens leading to transient hyperprolactinaemia. In contrast to this, MC-induced hyperprolactinaemia during the mid-follicular (4 d) or early luteal phase of the cycle did not alter the concentrations of cytosol or nuclear oestrogen and progestin receptors or the activity of 17 beta-hydroxysteroid dehydrogenase in endometrial tissue. Thus, transiently elevated circulating PRL does not seem to have direct effects on female sex steroid receptors or their function in the proliferative or secretory endometrium.

17-Hydroxysteroid Dehydrogenases↗

Collagen metabolism in normal and complicated pregnancy: changes in the aminoterminal propeptide of type III procollagen in serum.

The turnover of type III collagen, a major constituent of the myometrium and the uterine cervix, during pregnancy was evaluated by monitoring serum antigens related to the aminoterminal propeptide of type III procollagen. Their concentration increased markedly towards term in most uncomplicated pregnancies, while their size distribution throughout the pregnancy resembled that seen in the sera of normal healthy persons. In some patients, however, the level remained low, indicating interindividual variation in the release into serum and metabolism of the propeptide. There were no distinct changes during or immediately after vaginal delivery. Values exceeding the reference range for uncomplicated pregnancies were found during weeks 28-37 in patients with pre-eclampsia, essential hypertension, intrahepatic cholestasis of pregnancy or twin pregnancy. Thus, pregnancy should be taken into account when evaluating results of the serum assay for the aminopropeptide and the use of this assay as an indicator of pregnancy complications warrants further study.

Cholestasis↗

Characterization of human fetal hepatic cytochrome P-450-associated 7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase activities by monoclonal antibodies.

Two cytochrome P-450-dependent enzyme activities, 7-ethoxyresorufin O-deethylase (ERDE) and aryl hydrocarbon hydroxylase (AHH) were measured in liver microsomes from 7 human fetuses. Monoclonal antibodies (MAb) to a 3-methylcholanthrene-induced (MAb 1-7-1) and a phenobarbital-induced (MAb 2-66-3) rat hepatic cytochrome P-450 were used to measure the contribution of the MAb-defined, epitope-specific cytochromes P-450 to the total reaction measured for the above activities. MAb 1-7-1 inhibited fetal hepatic ERDE activity to a variable extent (from 0 to 100%, 34 in average), but had only negligible effects on AHH activity (mean inhibition 9%). The contribution of induction by cigarette smoking to the variability of ERDE inhibition by MAb 1-7-1 remained unclear. MAb 2-66-3 inhibited ERDE activity by 18% and AHH activity by 12%. In comparisons with earlier studies on adult liver and placental microsomes, the present results with fetal liver suggest that there are differences in cytochrome P-450-associated ERDE and AHH activities between these tissues, which might be due to different tissue-specific isoenzyme patterns.

Antibodies, Monoclonal↗

Isolated prolactin deficiency in a woman with puerperal alactogenesis.

Idiopathic PRL deficiency was detected in a parturient woman with otherwise normal pituitary function. This PRL disorder first became manifest postpartum when she had no milk production, and oral metoclopramide failed to raise her serum PRL levels. Her second pregnancy occurred spontaneously after 3 yr of attempts to conceive. During the pregnancy, her serum PRL concentration was very low, varying from 4.5-7.8 ng/ml, and the puerperium was again characterized by alactogenesis. During normal menstrual cycles and after iv GnRH, TRH, metoclopramide, and insulin tolerance tests, serum PRL was only rarely detectable by RIA, at very low concentrations. Bioassay results confirmed the PRL deficiency. The results confirm that PRL is necessary for puerperal lactation and suggest that it is needed for normal ovarian function. The present data also suggest that the maternal pituitary is the main source of serum PRL during pregnancy, and the decidua has only a minor contribution in this respect.

Adult↗

Inverse seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity.

The effects of season on the activity of the pituitary-ovarian axis and the pineal gland were studied in 11 women by serum and urinary melatonin determinations and in 21 women by measurements of the serum concentrations of anterior pituitary and ovarian hormones during the dark and light seasons. A melatonin index was determined by integration of the area below the curve of serum melatonin concentrations during 24-h periods in both seasons. During the dark season, the daytime 12-h melatonin index and daytime urinary melatonin excretion were significantly higher than during the light season. In addition, the duration of the nocturnal melatonin pulse (serum melatonin levels, greater than 65 pmol/L) was lengthened during this season, whereas the mean serum estradiol concentration was significantly decreased at the time of ovulation and during the luteal phase of the cycle, indicating lowered ovarian activity. Luteal phase gonadotropin concentrations were increased during the dark season, which was also characterized by increased sex hormone-binding globulin (SHBG) and decreased free testosterone concentrations and free androgen indices (ratio of testosterone to SHBG X 700) throughout the menstrual cycle. The dark season was thus characterized by increased melatonin secretion and decreased ovarian and androgenic activities. In summary, we characterized two season-dependent hormonal phenomena. Although we did not prove any cause and effect association between melatonin and anterior pituitary-ovarian hormones, the inverse seasonal relationship in pineal gland and ovarian secretion suggests that melatonin is causally related to reproduction in humans.

Adult↗

Intracavitary irradiation of endometrial cancer of large uteri using a two-phase afterloading technique.

A specific intracavitary two-phase technique was developed for irradiation of endometrial cancer located in uteri with a large uterine cavity. In this technique an insertion catheter (external diameter 9 mm) was used for the introduction and precise location of the treatment catheter (external diameter 6.4 mm). During the first phase of the therapy, one lateral half of the uterine body was irradiated. Thereafter the positions of the catheters were changed by 180 degrees, followed by irradiation of the other lateral half of the uterine body. Using a wax phantom and extirpated uteri as models, we observed that the dose distributions followed the uterine shape and the calculated doses in the radiographs. Clinical observations from 34 patients treated so far, and followed-up for periods of 3 months to 6 years, prove that this method yields similar results to those observed in previous studies employing the Heyman packing method or afterloading techniques with a one-source tandem in the intracavitary irradiation of endometrial cancer.

Brachytherapy↗

Serum concentrations of thyrotropin, thyroxine, triiodothyronine and thyroxine binding globulin in female endurance runners and joggers.

The effects of endurance training and season on the function of the anterior pituitary-thyroid axis were studied in 18 female runners and their 12 controls, and in 13 joggers and their 11 controls in Northern Finland, with a large seasonal difference in environmental factors. The serum concentrations of thyrotropin (TSH), thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), thyroxine binding globulin (TBG) and oestradiol (E2) were measured during one menstrual cycle in the light training season (autumn) and in the hard training season (spring). The responses of TSH to intravenous TRH stimulation were also measured in the luteal phase of the cycle during the hard training season. Endurance running did not affect the basal or TRH-stimulated serum TSH concentrations, while those of T4 and fT4 in runners were lowered in both seasons and that of T3 in the light training season in relation to control subjects. The serum concentrations of TBG were also significantly lower in runners than their controls in the luteal phase in both seasons. The effect of jogging on thyroid hormones was less pronounced. Serum concentrations of TSH, T4, fT4, T3 and TBG were generally slightly higher in spring than in autumn. Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training. In spring the function of anterior pituitary-thyroid axis is more active than in autumn.

Adult↗

The effect of season on the circulating concentrations of anterior pituitary, ovarian and adrenal cortex hormones and hormone binding proteins in the subarctic area; evidence of increased activity of the pituitary-ovarian axis in spring.

To evaluate the effects of season on the function of the pituitary-ovarian axis and the adrenal cortex in a northern area with great seasonal variation in the length of daylight, 10 healthy women were investigated over 1 menstrual cycle in spring (May-June), autumn (August-September), early winter (November-December) and late winter (February-March). Serum concentrations of LH, FSH, prolactin, estradiol, progesterone, total and free testosterone, cortisol, sex hormone binding globulin (SHBG) and cortisol binding globulin (CBG) were measured, and the indices of free estradiol (FEI), free androgen (FAI) and free cortisol (FCI) were calculated on cycle days 3-4, 6-7, 10-11, on the presumed day of ovulation, and 6-7 and 9-10 days after the presumed ovulation. Spring was the season that most significantly differed from the other seasons. It was characterized by a significantly decreased concentration of SHBG and an increased FAI throughout the whole menstrual cycle, an increased FSH concentration during the follicular phase, significantly increased estradiol concentration and an increased FEI, and significantly decreased concentrations of FSH and LH during the luteal phase of the cycle. The concentration of cortisol and the FCI were significantly increased in the autumn compared with late winter, both seasons having similar day-length. The present data demonstrate that spring, with a long photoperiod, seems to be associated with increased pituitary-ovarian axis activity and androgenic activity, whereas adrenal cortex function did not show any association with day-length.

Adrenal Cortex Hormones↗

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis.

A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis.

Adult↗

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery.

To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.

Analysis of Variance↗