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Biomedical subjects

A Tiitinen

Publications and source records attributed to A Tiitinen.

At least 37 records · Page 2Linked to original sources

A prospective study on women with a history of breast cancer and with or without estrogen replacement therapy.

OBJECTIVE: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausal patients with a history of breast cancer is not based on any research evidence and may be more harmful than beneficial, we evaluated the safety and efficacy of ERT in these women. METHODS: We recruited 131 patients who had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20 years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need for ERT. At recruitment, the patients were carefully examined for breast and gynaecologic findings. Non-hysterectomized patients wishing to receive ERT (n=54) then started using estradiol as oral tablets (2 mg/day) (n=44) or as transdermal gel (1.5 mg/day) (n=10) in combination with 10-day courses of oral medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients (n=34) used only estradiol, orally (2 mg/day) (n=31) or transdermally (1.5 mg/day) (n=3). The patients using ERT were carefully examined 6 and 12 months later, and then annually at a specific outpatient department, and the mean follow-up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The 43 patients not wishing to receive ERT were followed annually at the oncologic department for a mean of 2.6 years (range from 1 month to 4.7 years), and served as a control group. RESULTS: ERT significantly reduced climacteric symptoms, and the Kupperman score fell by 63%, from 26.9+/-8.6 to 9.9+/-6.7 (mean+/-SD). In non-hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding in all except seven women. Seven patients (13%) experienced spotting during ERT. In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54 patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3-6 months. Ten patients terminated the use of ERT within the first 12 to 39 months due to the lack of severe vasomotor symptoms (n=4) or due to the recurrence of breast cancer or to cancer of the contralateral breast (n=6). Eighty-one of the 88 patients (92%) using ERT showed no evidence of recurrence, whereas five patients (5.7%) had recurrence in 12-36 months and two patients (2.3%) developed a cancer of the contralateral breast in 14-24 months; another one of those wanted to continue with ERT. Thus the combined risk of recurrence or a new cancer of the contralateral breast in ERT users was 7/216 woman-years (3% per year). In the control group, 38 of 43 patients (88.4%) showed no evidence of recurrence or contralateral cancer, whereas four patients had recurrence and one developed a contralateral breast cancer (5/112 woman-years, 4% per year). CONCLUSIONS: Symptomatic climacteric patients with a history of breast cancer benefited from ERT without increasing their risk of recurrence, but the short follow-up and the small number of patients limit any definitive recommendations.

Administration, Cutaneous↗

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women.

To assess and compare the gynaecological consequences of the use of 2 antioestrogens we examined 167 postmenopausal breast cancer patients before and during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day, n = 83) as an adjuvant treatment of stage II-III breast cancer. Detailed interview concerning menopausal symptoms, pelvic examination including transvaginal sonography (TVS) and collection of endometrial sample were performed at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30 women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine artery was measured before and at 6 and 12 months of treatment. The mean (+/-SD) follow-up time was 2.3 +/- 0.8 years. 35% of the patients complained of vasomotor symptoms before the start of the trial. This rate increased to 60.0% during the first year of the trial, being similar among patients using tamoxifen (57.1%) and toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline, increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial thickness increased from baseline (3.9 +/- 2.7 mm) to 6.8 +/- 4.2 mm at 6 months (P< 0.001), and no difference emerged between the 2 regimens in this regard. Before the start of the antioestrogen regimen, the endometrium was atrophic in 71 (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign endometrial polyps. During the use of antioestrogen altogether 339 endometrial samples were taken (159 in tamoxifen group, 180 in toremifene group). The endometrium was proliferative more often in the tamoxifen group (47.8%) than in the toremifene group (32.2%) (P< 0.0001). 20 patients had a total of 24 polyps (17 in tamoxifen and 9 in toremifene group, P< 0.05) during the use of antioestrogens. One patient in the toremifene group developed endometrial adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the endometrium. Tamoxifen failed to affect the PI in the uterine artery, but toremifene reduced it by 15.0% (P< 0.05) by 12 months. In conclusion, tamoxifen and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen led to the development of premalignant endometrial changes. Our data suggest that so close endometrial surveillance as used in our study may not be mandatory during the first 3 years of use of antioestrogen treatment.

Aged↗

IVF treatments and their outcomes in Finland in the 1990s.

BACKGROUND: In vitro fertilization and its variants have become routine infertility treatments in industrialized countries. Our purpose is to summarize the procedures and treatment outcomes in Finland in the 1990s and to compare the results between public and private clinics. METHODS: The data came from the Finnish IVF statistics for 1992 to 1999. Most analyses were done for the years 1994 to 1998 for which identical data-collection sheets were used. RESULTS: In 1999, 12 of the 19 clinics offering assisted reproductive treatments were private. The number of treatments increased from 2,331 in 1992 to 7,213 in 1999. In total 58% were performed in the private sector. Most treatments were given for women aged 30 to 39 years, but in the private sector women were up to on average two years older. Most often care was given due to tubal factor or unexplained infertility (IVF) and due to male factor or multiple causes (ICSI). The number of transferred embryos decreased during the study period, but the transfer of two embryos was still most frequent. Three out of four IVF and ICSI pregnancies, and two out of three FET pregnancies ended in a live birth. The success rates improved for IVF and for ICSI after adjustment for the number of transferred embryos, but not for FET. Small but inconsistent differences were observed in the success rates between the private and public sectors. There was noticeable variation between clinics. CONCLUSION: The number of treatment cycles stabilized in the late 1990s. The success rates improved only slightly and the differences in outcome measures between private and public clinics were small. However, neither this nor the large clinical variation could be investigated more thoroughly without collecting individual register data.

Adult↗

Portfolios as a learning tool in obstetrics and gynaecology undergraduate training.

CONTEXT: We developed a structured portfolio for medical students to use during their obstetrics and gynaecology undergraduate training. The main objective was to support the learning process of the students. We also wanted feedback information to enhance teaching. METHODS: The study population consisted of 91 medical students who completed the portfolio during their training course. The portfolio consisted of a 28-page A5-size booklet. The students entered all the clinical procedures they had performed and all the deliveries they had attended. After each group session, they answered questions about what they had learned and evaluated the performance of the teacher. They also indicated their general evaluation of the course and the portfolio itself. The teachers listed the 13 most important skills to be learned during the course. The students were asked to evaluate their own development on a scale of 0-5 before and after the course. A content analysis was performed on all the texts the students produced, and all quantitative variables were coded. RESULTS: The amount of text written in the portfolio correlated (P < 0.001, F-value 4.2) with success in the final exam. In addition to acting as a logbook, use of the portfolio enhanced the learning process during the course. Students' attitudes towards the portfolio were mainly positive. Students appreciated the departmental interest in their learning process. CONCLUSION: Portfolios support the personal and professional development of medical students. A portfolio clarifies the learning goals and helps students to monitor how these goals are achieved. A portfolio encourages constant self-reflection.

Education, Medical, Undergraduate↗

Oral symptoms at menopause--the role of hormone replacement therapy.

OBJECTIVE: A questionnaire was used to investigate the prevalence of self-assessed sensations of painful mouth (PM) and dry mouth (DM) in menopause-aged women. Special attention was paid to the association of the use of hormone replacement therapy (HRT) with oral symptoms. Our hypothesis was that women using HRT have fewer oral symptoms than those who do not use HRT. STUDY DESIGN: Patients were selected from among 50- to 58-year-old women attending a communal mammography screening program in Helsinki, Finland. Every fifth woman was offered a structured questionnaire. RESULTS: Completed questionnaires were received from 3173 women (response rate, 65%). Of the total sample, 46.8% (n = 1486) used HRT. The occurrence of PM was 8.2% (n = 259) and DM, 19.9% (n = 631). Climacteric symptoms were reported by 24% (n = 761) of the total sample and by 19.2% (n = 285) of the HRT users. According to logistic regression analyses, climacteric symptoms were found to be predictive of PM (P =.000) and DM (P =.000). The use of HRT also increased the occurrence of PM (P =.03). However, as a single covariate in our statistical model, the use of HRT was not a predictor of PM. The use of HRT also did not correlate with the occurrence of DM. CONCLUSIONS: The occurrence of PM and of DM seemed to be associated with climacteric symptoms in general, and the use of HRT did not prevent the oral symptoms studied.

Age Factors↗

The predictive value of pronuclear morphology of zygotes in the assessment of human embryo quality.

BACKGROUND: Recent studies have shown that zygote morphology could be used for the assessment of human embryo quality. Pronuclear (PN) morphology is based on certain distinct features seen in zygotes 16-18 h after fertilization. In the present study PN stage morphology was assessed and combined with a single embryo transfer in order to investigate whether currently used zygote classifications are able to predict embryo quality and implantation rates. METHODS AND RESULTS: Zygotes were analysed according to two different classification systems. In the first, a total of 764 zygotes was analysed according to the degree of polarization of nucleolar precursor bodies (NPB). Zygotes with unpolarized PN (i.e. scattered localization of NPB) showed significantly slower (P < 0.005) cleavage rates (38.9%) than zygotes having at least one pronucleus polarized (57.3% and 54%). However, there was no difference in the pregnancy rate in 105 single embryo transfers between the groups. The appearance of a cytoplasmic halo was related to embryo morphology. Embryos derived from halo-positive zygotes had significantly better (P < 0.05) morphology (60.9%) compared to halo-negative derived embryos (52.2%), but in terms of pregnancy rates no difference was found. A total of 1520 zygotes was analysed according to a second classification system, which was based on the number and distribution of NPB. In the comparative analysis, none of the six different classes produced superior quality embryos or higher pregnancy rates in 144 single embryo transfers. CONCLUSIONS: Our results indicate that there are no significant differences in embryo quality or implantation/pregnancy rates between proposed zygote classes.

Cell Nucleolus↗

Obstetric outcome in women with polycystic ovarian syndrome.

Women with polycystic ovarian syndrome (PCOS) often have insulin resistance and hyperinsulinaemia and may therefore be at an increased risk for gestational diabetes mellitus (GDM). Hyperinsulinaemia may also be associated with pre-eclampsia. Information concerning outcome of pregnancies in PCOS women is scanty and somewhat controversial. Therefore, 99 pregnancies were retrospectively evaluated in women with PCOS and the findings were compared with an unselected control population. The average body mass index (BMI) in PCOS patients was greater than that in controls (25.6 versus 23.0) (P < 0.0001), and PCOS patients were more often nulliparous than controls (76 versus 42%) (P < 0.001). The multiple pregnancy rate was 9.1% in PCOS patients and 1.1% in controls [odds ratio (OR) 9.0; 95% confidence interval (CI) 3.5-23.3]. GDM developed in 20% of the PCOS patients and in 8.9% of the controls (P < 0.001). After logistic regression analysis, BMI >25 seemed to be the greatest predictor for GDM (adjusted OR 5.1; CI 3.2-8.3), while PCOS remained as another independent predictor (adjusted OR 1.9; CI 1.0-3.5). In contrast, PCOS was not a significant predictor for pre-eclampsia, which was merely associated with nulliparity. Premature delivery (16.1% in PCOS and 6.5% in controls) was explained to a large extent by multiple pregnancies and marginally by nulliparity and PCOS. In singleton pregnancies, there was no difference in birth weights, Apgar scores or perinatal morbidity of infants. In conclusion, PCOS slightly increases the risk for GDM, but does not have an important effect on the rate of premature delivery and pre-eclampsia.

Adult↗

Leptin during assisted reproductive cycles: the effect of ovarian stimulation and of very early pregnancy.

Leptin may have a role in human reproduction. The impact of IVF and of very early pregnancy on serum leptin concentrations was studied in 66 infertile patients, of whom 19 became pregnant. Ovarian suppression was accompanied by a fall in leptin concentrations (21 +/- 4%, mean +/- SE; P < 0.01) from the mid-luteal phase, and ovarian stimulation by a rise (76 +/- 8%; P < 0.0001) from suppression. The mid-luteal concentration of leptin after stimulation was 28 +/- 7% higher than that during the preceding normal cycle (P < 0.001). Concentrations of leptin and oestradiol were related before treatment, at ovarian suppression and at 8 days after oocyte retrieval. In addition, the rises in leptin and oestradiol concentrations during stimulation were correlated, but only in those patients who became pregnant (r = 0.69; P = 0.001). Women with a successful pregnancy had higher concentrations of leptin (18.7 +/- 4.8 microg/l) at 12 days after embryo transfer than those who had miscarriages (10.0 +/- 1.9 microg/l; P < 0.001), or those failing to become pregnant (11.6 +/- 1.2 microg/l; P < 0.0001). We concluded that leptin concentrations are influenced by ovarian function and that the relationship between leptin and oestrogen (but not a single leptin concentration), may be an important factor for the outcome of IVF.

Adult↗

Elective single embryo transfer: the value of cryopreservation.

In-vitro fertilization is associated with a high rate of multiple pregnancies, a consequence of the number of embryos transferred. There is a challenge in avoiding even twin pregnancies in assisted reproduction, and this can be accomplished with elective single embryo transfer and a good cryopreservation programme. In our follow-up study, we analysed all our elective single embryo transfers during 1998-1999. In all these cycles at least one embryo was frozen. A total of 127 elective single embryo transfers were performed with a clinical pregnancy rate of 38.6%. The highest implantation rate was obtained with four-cell embryos with <10% fragmentation (39.8%). Thirty-four patients have delivered (26.8%), one of these being a monozygotic pregnancy. In total 129 frozen-thawed cycles have been achieved in 83 patients. One frozen-thawed embryo has been transferred in 46 cycles with a clinical pregnancy rate of 17.4%, and two embryos have been transferred in 83 cycles, with a clinical pregnancy rate of 37.3%. Up until now, 66 of 125 patients in our single embryo transfer programme have delivered or have on-going pregnancies, and 77 still have embryos frozen. The cumulative delivery rate per oocyte retrieval is 52.8% and the twin rate 7.6%. We conclude that elective single embryo transfer with a good cryopreservation programme results in very acceptable pregnancy rates with a low risk of twins. This is a cost-effective practice that substantially reduces all risks associated with multiple pregnancies and lowers the cost per delivery.

Cost-Benefit Analysis↗

One versus two embryo transfer after IVF and ICSI: a randomized study.

BACKGROUND: The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups. RESULTS: The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS: Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.

Adult↗

Sexual function and fertility in adult females and males with congenital adrenal hyperplasia.

Female patients with classic 21-hydroxylase deficiency (21-OHD) present with decreased fertility and low childbirth rates, women with a salt-wasting form of 21-OHD being most severely affected. In cases of undersubstitution with glucocorticoids, tonic androgen secretion disturbs ovulation. However, even adequately substituted females may present with apparent infertility. Despite adrenal androgen suppression, adrenal progesterone secretion can prevent thickening of the endometrium in the follicular phase. Furthermore, functional ovarian hyperandrogenism is a common finding even in women with well-controlled classic 21-OHD. Psychosexual factors may also contribute significantly to decreased childbirth rates found in these patients. Genital ambiguity may lead to a disturbed body image and the patients have been found to feel less feminine than healthy control women. The repeated psychological insult caused by frequent genital examinations and operations is also important, though its exact impact has been difficult to determine. Finally, prenatal androgen excess can cause masculinization of the central nervous system leading to boyish behavior in childhood and decreased heterosexual activity in adulthood. Some recent reports show a high rate of infertility also in men with 21-OHD. They are at risk of benign testicular tumors, adrenal rests, which can lead to permanent infertility. Also, raised adrenal androgen production leading to increased estrogen concentrations can suppress gonadotropin secretion and may lead to a hypogonadotropic state.

Adrenal Hyperplasia, Congenital↗

Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid esters in low-density lipoprotein particles.

Estrogens are known to be powerful antioxidants in lipid-aqueous systems, as demonstrated by their inhibition of low-density lipoprotein (LDL) oxidation in vitro. Studies reporting that endogenous human estrogens could be rendered fat-soluble by esterification with fatty acids in vivo, and the subsequent detection of such esters in blood and fat tissue suggested a possible mechanism explaining how estrogens might protect LDL. Because of their lipophilicity, esterified estrogens may become incorporated in the lipoprotein structure, providing antioxidant potential for the particles. We incubated labeled 17beta-estradiol with ovarian follicular fluid and with plasma in the absence and presence of the LCAT inhibitor DTNB. This was followed by ultracentrifugal isolation of LDL and high-density lipoprotein and analysis of the radioactive label in the "ester" and "free" fractions purified from these lipoproteins. The results indicated that LCAT-mediated synthesis of esterified 17beta-estradiol occurred in high-density lipoprotein particles, and suggested a novel cholesterol ester transfer protein-mediated mechanism for their transfer to LDL particles.

Carrier Proteins↗

Quantitative determination of estradiol fatty acid esters in human pregnancy serum and ovarian follicular fluid.

BACKGROUND: Lipophilic estradiol derivatives carried by lipoprotein particles in blood may mediate antioxidant or endocrine effects. We developed a new quantitative method to determine the concentration of circulating lipophilic estradiol fatty acid esters in human early- and late-pregnancy serum and in ovarian follicular fluid. METHODS: After extraction from serum or follicular fluid, estradiol fatty acid esters were separated from nonesterified estradiol by Sephadex LH-20 column chromatography. The estradiol ester fraction was hydrolyzed by saponification and further purified by several chromatographic steps. The hydrolyzed estradiol esters were measured by time-resolved fluoroimmunoassay. RESULTS: The average estradiol fatty acid ester concentration in serum increased 10-fold during pregnancy, from 40.4 pmol/L (expressed as pmol/L estradiol; range, 25.0-64.2 pmol/L) in early pregnancy (n = 8) to 404 pmol/L (196-731 pmol/L) in late pregnancy (n = 10). The ratio of estradiol ester to nonesterified estradiol remained relatively constant during pregnancy, at 0.4-0.6%. In 10 follicular fluid samples, the mean estradiol ester concentration was 106 nmol/L (56.9-262 nmol/L). Compared with serum, a greater proportion of estradiol in follicular fluid (3.0-10%) was in the esterified form. CONCLUSION: The new method provides a means to measure circulating estradiol fatty acid ester concentrations in human pregnancy serum.

Esters↗

Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients.

OBJECTIVES: Because estrogens stimulate the synthesis and release of leptin in the adipocytes, the effect of antiestrogens on the circulating leptin levels were studied. METHODS: Thirty postmenopausal patients with breast cancer were randomized to start either with tamoxifen (20 mg/day, n=15) or toremifene (40 mg/day, n=15), and the patients were examined and serum leptin concentrations measured before the study and at 6 and 12 months. RESULTS: The baseline leptin concentrations ranged from 4.4 to 60.0 microg/l (15.3+/-13.1 microg/l, mean+/-S.D.), and it correlated positively with the body mass index (BMI) of the subjects (r=0.73, P=0.0001). Taking as a whole the antiestrogen regimen was associated with elevated leptin levels at 6 months (19.5+/-13.8 microg/l, P=0.0001) but no excess increase in leptin levels were seen at 12 months (20.9+/-13.5 microg/l, NS). Subgroup analysis showed no difference between the effects of tamoxifen or toremifene on leptin. BMI increased in 21 women (from 26.2+/-4.3 to 27.3+/-4.8 kg/m2, P=0.0001) at 6 months, but not after that; in nine women BMI did not change. There was no significant correlation between the change in leptin levels and the change in BMI in either group implying that antiestrogens may specifically stimulate leptin production. CONCLUSIONS: Antiestrogens may stimulate the synthesis and release of leptin in the adipocytes. This effect of antiestrogens resembles the effect of estrogen and consequently stimulation of leptin production can be added to the estrogenic effects of antiestrogens.

Antineoplastic Agents, Hormonal↗