Risto Erkkola

When does estrogen replacement therapy improve sleep quality

OBJECTIVE Our purpose was to evaluate the effect of estrogen replacement therapy on sleep complaints by postmenopausal women and to assess the predictive factors involved. STUDY DESIGN Sixty-three postmenopausal women entered a 7-month prospective, randomized, double-blind, crossover study consisting of two 3-month treatments with estrogen and placebo with a 1-month washout period between. Eight Visual Analogic Scale statements about different sleep complaints, the Basic Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression Inventory, and serum estradiol and follicle-stimulating hormone level controls were the main outcome measures. RESULTS Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p < 0.001). The subjects were less tired in the mornings and in the daytime (p < 0.001) when taking estrogen replacement therapy. Estrogen-induced sleep improvement was associated with alleviation of vasomotor symptoms (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range 0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia predicted only one estrogen-induced sleep improvement effect: the more the subjects experienced insomnia, the better the estrogen replacement therapy facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep improvement was also reported by the 15 climacterically asymptomatic subjects. In these subjects initial insomnia scores strongly predicted estrogen-induced sleep improvement (r range 0.50 to 0.75). CONCLUSIONS Estrogen replacement therapy significantly diminished sleep complaints among postmenopausal women. Alleviation of climacteric symptoms was the most important predictive factor for the beneficial effect of estrogen replacement therapy on sleep complaints. The use of estrogen replacement therapy in women without self-reported climacteric symptoms could also be considered because women do not always recognize their climacteric symptoms or they ignore them.

Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women☆

Abstract Objective: To evaluate the effect of estrogen replacement therapy on sleep architecture, arousals, and body movements. Design: A 7-month, prospective, randomized, double-blind, placebo-controlled crossover trial. Setting: Departments of obstetrics and gynecology and a university sleep center in Turku, Finland. Patient(s): Seventy-one postmenopausal women, 4 of whom were excluded and 5 of whom withdrew from the study; the final study group consisted of 62 women. Intervention(s): Two periods of treatment with either estrogen or placebo. Main Outcome Measure(s): Polysomnography for measurement of sleep and arousals and a static charge–sensitive bed for monitoring of movements and breathing. Self-reports of climacteric symptoms for 14 days. Result(s): Estrogen effectively alleviated hot flashes, sweating, sleep complaints, and headaches. Estrogen decreased the total frequency of movement arousals but increased alpha-arousals, especially during light non–rapid eye movement sleep (stage 1). Sleep latency, distribution of sleep stages, sleep efficiency, and total sleep time were similar during treatment with estrogen and placebo. Changes in serum E 2 concentrations correlated with neither subjective nor objective sleep quality. Conclusion(s): Estrogen replacement therapy improves objective sleep quality by alleviating the frequency of nocturnal movement arousals. It also reduces climacteric symptoms, especially vasomotor symptoms. Estrogen replacement therapy does not seem to have any effect on sleep architecture.

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.

Frequency of anal sphincter rupture at delivery in Sweden and Finland ‐ result of difference in manual help to the baby's head

BACKGROUND Anal sphincter rupture is a serious complication of vaginal delivery and almost half the affected women have persistent defecatory symptoms despite adequate primary repair. During the past decade, the incidence of anal sphincter ruptures has been increasing in Sweden and is currently estimated to occur in 2.5% of vaginal deliveries. The aim of the study was to report the frequency of anal sphincter ruptures in two university hospitals in two Scandinavian countries, Malmö in Sweden and Turku in Finland, and analyze the potential determinants. METHODS Retrospective analysis of a population of 30,933 deliveries (26,541 vaginal) during the years 1990 to 1994. RESULTS The incidence of anal sphincter ruptures in Malmö, Sweden was 2.69%, and in Turku, Finland 0.36%. There were no significant population differences for the known risk factors (fetal weight, nulliparity or fetal head circumference). However, there is a difference in manual support given to the perineum and to the babys head when crowning through the vaginal introitus between Malmö and Turku. The proportion of operative vaginal deliveries and abnormal presentations was significantly higher in Turku reflected in the lower Apgar score at 5 minutes and longer duration of second phase of labor. When high risk deliveries (operative vaginal delivery, abnormal presentation and newborns over 4,000 g) were excluded, the risk for anal sphincter ruptures was estimated to be 13 times higher in Malmö than in Turku. CONCLUSIONS The difference in the incidence of anal sphincter rupture between Malmö, Sweden and Turku, Finland may be due to the difference in manual control of the babys head when crowning.

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.

Climacteric symptoms and sleep quality.

OBJECTIVE To evaluate the effect of climacteric vasomotor symptoms on sleep quality measured by self-report and polysomnography in postmenopausal women. METHODS Seventy-one healthy postmenopausal women were recruited, of whom 63 completed the study. Each subject recorded climacteric symptoms and subjective sleep quality for 14 days. Sleep quality was evaluated objectively by all-night polysomnography using the static charge-sensitive bed. RESULTS During polysomnography, a high frequency of climacteric vasomotor symptoms was not associated with changes in sleep latency, percentage of sleep stages, number of arousals, sleep efficiency, or total sleep time. However, a high frequency of climacteric vasomotor symptoms (range 0-8.9, r = .60, P < .001), somatic symptoms (range 0-5.0, r = .25-.44, P < .05), and mental symptoms (range 0-5.0, r = .41-.51, P < .001) was related to impaired subjective sleep quality. In stepwise regression analysis, 32% of the impairment in subjective sleep quality was explained by vasomotor symptoms (P < .001), 14% by palpitations (P < .001), and 4% by mood instability (P = .029). High body mass index predicted impaired objective sleep quality, such as prolonged latencies to stage-2 sleep (r = .27, P = .031) and slow-wave sleep (r = .51, P = .003) and decreased oxygen saturations (r = -.54, P < .001). Older women had decreased sleep efficiency (r = -.27, P = .030) and lower oxygen saturations (r = -.36, P = .004). Serum estradiol level had only a minor effect on objective sleep quality. CONCLUSION Impaired subjective sleep quality associated with climacteric vasomotor symptoms did not manifest as abnormalities in polysomnographic sleep recordings. Body mass index and age appeared to have the strongest effect on objective sleep quality.

Autonomic cardiovascular control in pregnancy

Pregnancy is associated with profound adaptive changes in the maternal hemodynamics. Although the autonomic nervous system plays a central role in the adaptation of the cardiovascular system to various needs, its role in the adaptation of the circulation to the demands of pregnancy is poorly understood. This paper reviews the literature of autonomic cardiovascular control in pregnancy as studied with the cardiovascular reflex tests. A Medline search and manual cross-referencing for prior publications were used. All papers found on the hemodynamic effects of the Valsalva maneuver, the orthostatic test, the deep breathing test, the isometric handgrip test and maternal heart rate variability in pregnancy were reviewed and all publications that studied short-term changes in maternal heart rate and blood pressure were included. The beginning of pregnancy is associated with sympathetic reactivity, whereas the latter half of pregnancy is characterized by increased hemodynamic stability during orthostatic stress. The heart rate response to the Valsalva maneuver is blunted in mid-pregnancy, possibly due to changes in the baroreflex and increased maternal blood volume. Heart rate variability is significantly reduced in the second trimester. Cardiovascular reflex tests can be used to study drug effects on maternal circulation non-invasively.

Expression of insulin-receptor substrate-1 and -2 in ovaries from women with insulin resistance and from controls

OBJECTIVE To evaluate the role of insulin-receptor substrate (IRS)-1 and -2 in ovary dysfunction in women with insulin resistance. DESIGN Immunoblotting and immunohistochemical analyses of the localization and staining intensity of IRS-1 and IRS-2 in the ovaries of women with the polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. SETTING Department of Obstetrics and Gynecology, Turku University Central Hospital. PATIENT(S) Sections of ovary were obtained at the time of cesarean section from five volunteers without medical complications and three patients with gestational diabetes mellitus. Paraffin-embedded ovary sections were selected from those on file from the department of pathology; four were from women with a histologic diagnosis of PCOS and seven were from women with endometriosis (controls). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Protein expression of IRS in human ovary samples. RESULT(S) Immunoblotting with specific monoclonal and polyclonal antibodies showed the presence of 165-kDa and 183-kDa proteins that corresponded to the size of IRS-1 and IRS-2, respectively, in normal pregnant ovaries and human cultured follicles. Immunohistochemical staining showed that positive IRS-2 expression in antral follicles was restricted to theca internal cells in ovulatory ovaries but was distributed widely in all compartments of follicles in different stages in polycystic ovaries. Compared with follicles at a similar stage of development in ovulatory ovaries, follicles in polycystic ovaries showed decreased staining for IRS-1 in granulosa cells but increased staining for IRS-2 in theca internal cells. These features of IRS-1 and -2 expression were also noted in preantral and atretic follicles from patients with gestational diabetes mellitus compared with those who had uncomplicated pregnancy. CONCLUSION(S) This study highlights a shift of the follicular insulin signal protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestational diabetes mellitus.

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.

Optimal use of hormone determinations in the biochemical diagnosis of the polycystic ovary syndrome.

OBJECTIVE To investigate, using logistic regression analysis and receiver operator characteristic analysis, the biochemical diagnosis of polycystic ovary syndrome (PCOS) and if it could be improved by using an array of hormone measurements chosen to yield optimal and cost-effective discrimination between women with PCOS and healthy women. DESIGN Retrospective clinical study. SETTING Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS Fifty-four oligomenorrheic women with PCOS diagnosed by ovarian ultrasonography, and 29 healthy regularly menstruating women with normal ovarian morphology. MAIN OUTCOME MEASURES Concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin in serum. RESULTS Luteinizing hormone, FSH and A, when used in combination, were the hormonal analytes of highest clinical utility. Diagnostic sensitivity, specificity, and overall concordance of 98%, 93%, and 96%, respectively, were attained. Each of the analytes used alone yielded lower degree of discrimination. CONCLUSIONS Simultaneous use of the levels of LH, FSH, and A in serum can be used effectively for classification between women with PCOS and healthy women.