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Biomedical subjects

Risto Erkkola

Publications and source records attributed to Risto Erkkola.

17 recordsLinked to original sources
PubMed2006

Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures.

BACKGROUND: Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells. The aim of this study was to investigate the effects of 17beta-estradiol and medroxyprogesterone acetate on proliferation, apoptosis, expression of differentiation markers and steroid hormone receptors in breast epithelium using an in vitro model of freshly isolated human breast tissue, in which a proper interaction of breast epithelium and stroma has been maintained. METHODS: Human breast tissues were obtained from women undergoing surgery for breast tumours. Peritumoral tissues were excised and explants were cultured for 3 weeks in medium supplemented with E2 or MPA or with E2+MPA. Endpoints included histopathological, histomorphometric and immunohistochemical assessment of the breast explants. RESULTS: Culture of breast explants for 14 or 21 days with steroid hormones increased proliferative activity and the thickness of acinar and ductal epithelium. E2-treatment led to hyperplastic epithelial morphology, MPA to hypersecretory single-layered epithelium and E2+MPA to multilayered but organised epithelium. The proliferative response to E2 in comparison to control (p < 0.001) was more pronounced than to MPA (p < 0.05) or E2+MPA (p < 0.05) at 7 and 14 days for Ki-67 and PCNA. E2 treatment also decreased the proportion of apoptotic cells after 7 (p < 0.01) and 14 (p < 0.01) days. In addition, the relative number of ERalpha, ERbeta and PR positive epithelial cells was decreased by all hormonal treatments. CONCLUSION: Organ culture system provides a model for studying the direct effects of steroid hormones and their analogues on postmenopausal human breast tissue. Addition of E2 or MPA or E2+MPA to breast explants caused characteristic changes in morphology, stimulated epithelial proliferation, lowered apoptosis ratio and decreased the relative number of epithelial cells expressing ERalpha, ERbeta and PR.

Apoptosis↗
PubMed2006

Estrogen therapy and cognition: a 6-year single-blind follow-up study in postmenopausal women.

The authors evaluated the effect of long-term hormone therapy (HT) on cognition in 60 postmenopausal women (aged 53 to 72 years) in a single-blind, 6-year follow-up study. The subjects were divided into three groups: non-HT users, continuous HT users, and irregular HT users. Measures of verbal and visuomotor skills, verbal and visual memory, and attention were used. All women had well-maintained cognitive performance. Long-term HT did not affect cognition, either for better or for worse.

Cognition↗
PubMed2006

Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women.

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2-4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.

Biomarkers↗
PubMed2006

Hazards associated with pregnancies and deliveries in lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is an autosomal recessive transport disorder of the dibasic amino acids. The defect leads to deficiency of lysine, arginine, and ornithine and, secondarily, to a functional disorder of the urea cycle. Transient postprandial hyperammonemia and subsequent persistent protein aversion, linked with several other biochemical and clinical characteristics of the disease, suggest an increased risk for maternal and fetal complications during pregnancy and delivery. Our unique material on the outcomes of 18 pregnancies of 9 Finnish mothers with LPI and the follow-up of their 19 children shows that maternal LPI is truly associated with increased risk of anemia, toxemia, and intrauterine growth retardation during pregnancy and bleeding complications during delivery. Successful pregnancies and deliveries can still be achieved with careful follow-up of blood pressure and laboratory values. The children of the mothers with LPI generally develop normally. Special care of maternal protein nutrition and control of ammonemia, anemia, and toxemia during pregnancy are essential. We propose centralization of deliveries to obstetric units with capability to deal with bleeding complications and rare inborn errors of metabolism.

Adult↗
PubMed2006

[Therapeutic effects of Jinqi Jiangtang tablet on women with polycystic ovary syndrome].

OBJECTIVE: To observe the therapeutic effects of Jinqi Jiangtang Tablet (JQJTT), a commonly prescribed recipe for type 2 diabetes in traditional Chinese medicine, on obese women with polycystic ovary syndrome (PCOS). METHODS: Twenty-four obese women with PCOS were prescribed JQJTT for 3 months and the changes of carbohydrate metabolism and biochemical indicators, including menstrual cycle, body mass index (BMI), the level of blood sex hormone, area under curve (AUC) of glucose and insulin during oral glucose tolerance test (OGTT), and testosterone responses during human chorionic gonadotrophin stimulation ovary test were observed. RESULTS: After treatment, there were significantly reductions in BMI (P<0.05), serum glucose level at 30 min during OGTT (P<0.05) and testosterone levels at eighteen hours during human chorionic gonadotrophin stimulation ovary test (P<0.05). In addition, nine patients had improved cycles among sixteen completed patients, and one patient with clomifene resistance got pregnant with response to clomifene treatment. CONCLUSION: The beneficial effects of JQJTT may result from improvement of carbohydrate metabolism and reduction in androgen biosynthesis in women with PCOS.

Adolescent↗
PubMed2005

Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women.

OBJECTIVE: To compare ospemifene and raloxifene regarding their effects on hormones, lipids, genital tract, and tolerability in postmenopausal women. DESIGN: A randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) of ospemifene or 60 mg (n = 29) of raloxifene for 3 months. RESULTS: There were no significant differences in the baseline characteristics between study groups. In comparison with raloxifene, follicle-stimulating hormone levels decreased significantly more in the 90-mg ospemifene group and sex hormone-binding globulin levels increased more in all ospemifene groups. Total cholesterol and low-density lipoprotein cholesterol levels decreased more in raloxifene than in ospemifene groups, although the difference in low-density lipoprotein cholesterol between 90-mg ospemifene and raloxifene was not significant. Endometrial thickness did not change in any study group and endometrial biopsies showed atrophy in the majority of subjects at 3 months. All ospemifene groups demonstrated a clear estrogenic effect on the vaginal epithelium, as seen in Pap smears. This was in sharp contrast to the raloxifene group, which had no effect on the vaginal epithelium. Kupperman index decreased in all study groups during treatment. The adverse events were mild, mainly single cases, and no clustering of events was observed. There were no clinically significant abnormal findings in laboratory safety parameters. CONCLUSIONS: Ospemifene, at the dose of 90 mg/day, was more estrogenic than raloxifene, as shown by changes in serum follicle-stimulating hormone and sex hormone-binding globulin levels. Neither agent stimulated endometrium, but in contrast to raloxifene, ospemifene had a clear estrogenic effect in the vagina. Further studies with ospemifene are needed in subjects with vaginal atrophy.

Double-Blind Method↗
PubMed2005

Role of progestins in contraception.

Progestins have been used for contraception for more than 30 years. The main goal was to develop a contraceptive method devoid of the metabolic or clinical side-effects associated with the use of estrogens. The development of new contraceptive methods and formulations is time-consuming and requires devotion, belief, and also strong economical basis. As a result of this endeavor new methods have been developed: oral progestins, implants, injectables, intrauterine hormonal systems, and vaginal rings. Progestin-only contraceptives may be preferable in some situations, which have absolute or relative contraindications to estrogen, side-effects to estrogen containing hormonal contraception, lactation, and comfort and feasibility of formulations for long-term use. At present, emergency contraception is also performed with progestin.

Cervix Mucus↗
PubMed2004

Sleep and the menopause.

Sleep problems and their consequences are a serious public health issue, imposing a substantial burden on the individual and society. Although sleep occupies one-third of our lives and can be considered to be an important subject, sleep medicine is a young speciality and problems are poorly investigated. Sleeping problems are frequently reported during the menopausal transition. Subjectively women find that hormone replacement therapy (HRT) significantly improves sleep quality. Thus, HRT can be considered as a first-line therapy for insomnia. However, in some cases insomnia coincides with the menopause transition and cannot be considered to result from ovarian failure. Depressive mood, stress and behavioural factors, as well as restless legs and periodic limb movement syndromes may be the underlying cause. Thus, if no relief with HRT has been achieved after a few months, other aetiologies should be explored.

Estrogen Replacement Therapy↗
PubMed2004

No increased risk of endometrial hyperplasia with fixed long-cycle oestrogen-progestogen therapy after five years.

OBJECTIVE: The aim of this study was to evaluate the long-term endometrial safety of long-cycle sequential oestrogen-progestogen hormone replacement therapy (HRT). STUDY DESIGN: A prospective, longitudinal, single group study was undertaken in postmenopausal women, aged 45-66 years, treated with up to 21 3-month cycles (five years) of sequential oestrogen-progestogen HRT. Treatment consisted of 70 days of 2 mg/day oestradiol valerate (E(2)V), followed by 14 days of E(2)V combined with 20 mg/day medroxyprogesterone acetate (MPA), followed by seven days placebo. Endometrial biopsies were assessed at baseline, at 12 months in women with an endometrial thickness >6 mm and in all participants at 24, 36, 48 and 60 months. Mammography was performed at baseline and at 24-month intervals thereafter. Adverse events were assessed throughout the study. RESULTS: Of 132 women enrolled, 94 completed five years of treatment (540 women years). Endometrial changes (oestrogen effect II) were apparent in most women from 24-60 months (95, 83.3% women at 24 months). One case of simple hyperplasia was found (at 60 months), and none of complex hyperplasia or endometrial cancer. The pattern and frequency of adverse events were consistent with other sequential oestrogen-progestogen HRT regimens. CONCLUSIONS: The incidence of hyperplasia over five years (0.19%, upper 95% CI 0.88) was well within the acceptable rates defined by the European Union Committee for Proprietary Medicinal Products (CPMP).

Aged↗
PubMed2004

Fetal scalp pH and ST analysis of the fetal ECG as an adjunct to CTG. A multi-center, observational study.

OBJECTIVE: To evaluate the relationships between scalp-pH and CTG plus ST waveform analysis of the fetal ECG (STAN) clinical guidelines as indicators of intrapartum hypoxia in term fetuses born with cord artery acidemia. STUDY DESIGN: Data from 6999 term deliveries monitored by the STAN (R) S 21 as part of an EU multi-center study on clinical implementation of the STAN methodology for intrapartum fetal surveillance were analyzed. We identified 911 cases where a scalp-pH was obtained, including 53 cases with cord artery acidemia (pH < 7.06). Lag times between ST events and scalp-pH and time to delivery were related to cord artery metabolic and respiratory acidosis and neonatal outcome. RESULTS: 43 fetuses were identified by CTG plus ST as being in need of intervention 31 (25-46) minutes before delivery (median, 95% Cl). In five, no indications were given and in another five there were inadequate data. Fifteen cases with metabolic acidosis required special neonatal care, all 14 cases adequately monitored on STAN had indications to intervene for 19 minutes or more. In 30 adequately recorded cases, fetal blood sampling (FBS) was obtained within the last hour of labor. In 22 cases, FBS was obtained 13 (7-24) minutes after STAN guidelines had indicated abnormality and in eight no ST changes had occurred at time of FBS. The corresponding FBS data were pH 7.10 (7.01-7.15) and pH 7.21 (7.08-7.31), respectively, P = 0.01. In cases of metabolic acidosis, scalp-pH fell 0.01 units per minute after a baseline T/QRS rise was recorded during the second stage of labor. Apart from one newborn that died at 2 h from E. Coli septicemia, none of the neonates were affected neurologically. CONCLUSION: Cardiotocography plus ST analysis provides accurate information about intrapartum hypoxia similar to that obtained by scalp-pH.

Acidosis↗
PubMed2003

Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome.

OBJECTIVE: Insulin resistance is a common feature of both polycystic ovary syndrome (PCOS) and non-insulin-dependent diabetes mellitus (NIDDM); however, the persistent reproductive disturbances appear to be limited to the former, suggesting that insulin resistance in the ovary itself may confer this susceptibility. DESIGN: Prospective study. SETTING: University-affiliated department. PATIENT(S): Forty-four women undergoing IVF treatment, of whom 11 had polycystic ovaries and 33 had normal ovulation (NO). INTERVENTION(S): The various effects and signaling of insulin and insulin-like growth factor-1 (IGF-1) were examined in cultured ovarian granulosa cells treated with troglitazone (1 microg/mL) or with vehicle by reverse transcription-polymerase chain reaction, western blot, and in vitro functional analyses. MAIN OUTCOME MEASURE(S): Glycogen and DNA syntheses, mRNA and protein expression, and cellular localization of insulin/IGF-1 receptors and insulin receptor substrates (IRSs). RESULT(S): There were significant decreases in insulin-stimulated glucose incorporation into glycogen in PCOS cells, which is a metabolic action of insulin. However, IGF-1 stimulation was found to be greater in PCOS cells at all experimental concentrations with respect to thymidine incorporation compared with NO cells, which is a mitogenic action. Troglitazone increased the insulin-induced glycogen synthesis but reduced the IGF-1-augmented responses of DNA synthesis in PCOS cells to the range within those of NO granulosa cells. We then found that troglitazone treatment reversed the expression imbalance between IRS-1 and IRS-2 in PCOS cells. CONCLUSION(S): There is a selective defect in insulin actions in PCOS granulosa cells, which suggests ovarian insulin resistance, and this metabolic phenotype is associated with an enhanced IGF-1 mitogenic potential. Troglitazone could divergently alter expression of various IRS molecules and insulin actions and could be used as an ovarian insulin sensitizer and mitogen/steroidogenic inhibitor in PCOS.

Adult↗
PubMed2003

Breathing during sleep in menopause: a randomized, controlled, crossover trial with estrogen therapy.

OBJECTIVE: To evaluate the prevalence of different types of nocturnal breathing abnormalities in postmenopausal women and the effect of estrogen replacement therapy (ERT) on nocturnal breathing. METHODS: A prospective, randomized, placebo-controlled, double-blind, crossover study was completed by 62 of 71 recruited healthy women. The first 3-month treatment period with either estrogen or placebo was followed by placebo washout for a month and then by a second treatment period with crossover to either estrogen or placebo. On a night after each treatment period, sleep was monitored with polysomnography, and breathing was assessed with a static-charge-sensitive bed and oximeter. For the respiratory variables, a sample size of 48 subjects was sufficient to give statistical power of 85% with a significance level of P <.05. RESULTS: The occurrence of obstructive sleep apnea in all women was low (1.6%), but partial upper airway obstruction, manifesting as an increased respiratory resistance pattern, was more common (17.7%). Estrogen replacement therapy decreased the occurrence (P =.047) and frequency (P =.049) of sleep apnea but had no effect on partial upper airway obstruction or arterial oxyhemoglobin saturation. CONCLUSION: Partial upper airway obstruction is the most prevalent form of sleep-disordered breathing, occurring ten times more frequently than sleep apnea in postmenopausal women. Unopposed estrogen replacement therapy has only a minor effect on sleep apnea and has no effect on partial airway obstruction.

Cross-Over Studies↗
PubMed2002

No increased risk of endometrial hyperplasia with fixed long-cycle hormone replacement therapy after two years.

The appropriate dose of progestogen during long-cycle hormone replacement is still under debate. We present preliminary two-year results from an open five-year clinical trial of 132 postmenopausal women. All subjects had long-cycle HRT consisting of 70 days 2 mg oestradiol valerate (E(2)V), followed by 14 days 2 mg E(2)V plus 20 mg medroxyprogesterone acetate, and a seven-day hormone-free period. No endometrial samples with hyperplasia or indicative of malignancy were found at 24 months.

Journal Article↗
PubMedDate not supplied

Prevalence and fate of type 1 diabetes-associated autoantibodies in cord blood samples from newborn infants of non-diabetic mothers.

BACKGROUND: Cord blood samples were collected from 1002 consecutive births at Turku University Hospital to study the prevalence and fate of type 1 diabetes-associated autoantibodies in newborn infants of unaffected mothers. METHODS: The samples were analysed for cytoplasmic islet cell antibodies (ICA), autoantibodies to the 65 kD isoform of glutamic acid decarboxylase (GADA), autoantibodies to the protein tyrosine phosphatase related IA-2 antigen (IA-2A), insulin autoantibodies (IAA) and HLA DQB1 genotypes. RESULTS: ICA were detected in 27 cord blood samples (2.7%), with a median of 6 (range 4-34) JDF units. GADA were found to be positive (> or =6.6 RU) in six samples (0.6%), with a median of 66 (range 19-125) RU. IA-2A (> or =0.43 RU) were observed in three samples (0.3%), with a median of 1.3 (range 0.8-57) RU, while only one cord blood sample (0.1%) tested positive for IAA (> or =1.56 nU/ml) with a value of 5.4 RU. Maternal or gestational age, sex and birth weight of the infant were not related to antibody prevalence or titres. Altogether there were 29 infants with antibody positivity in their cord blood (2.9%). Five of these (0.5%) tested positive for two antibodies (ICA and GADA), and one was positive for all four antibodies measured. All nine infants from whom follow-up samples were available became antibody negative by the age of 15 months, and in all but one case inverse seroconversion occurred by the age of 9 months. CONCLUSIONS: Around 3% of infants of non-diabetic mothers in Finland have diabetes-associated autoantibodies at birth, and these antibodies disappear at the latest by the age of 15 months.

Adolescent↗