Takahisa Ushiroyama

Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women

OBJECTIVES To investigate the therapeutic effect of combined use of vitamin K(2) and D(3) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis. SUBJECTS AND METHODS We enrolled 172 women with vertebral bone mineral density <0.98 g/cm(2) (osteopenia and osteoporosis) as measured by dual-energy X-ray absorptiometry. In this study, we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996. Subjects were randomized into four groups (each having 43 subjects in vitamin K(2) therapy group, vitamin D(3) therapy group, vitamin K(2) and D(3) combined therapy group, or a control group receiving dietary therapy alone) and treated with respective agents for 2 years, with bone mineral density was measured prior to therapy and after 6, 12, 18, and 24 months of treatment. The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide (P1CP), serum intact osteocalcin, and urinary pyridinoline. Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time (APTT) and analysis of concentrations of antithrombin III (AT III), fibrinogen, and plasminogen. RESULTS Combined therapy with vitamin K(2) and D(3) for 24 months markedly increased bone mineral density (4.92 +/- 7.89%), while vitamin K(2) alone increased it only 0.135 +/- 5.44%. The bone markers measured, revealed stimulation of both bone formation and resorption activity. We observed an increase in coagulation and fibrinolytic activity that was within the normal range, suggesting that balance was maintained in the fibrinolysis-coagulation system. CONCLUSIONS Continuous combination therapy with vitamin K(2) and D(3) may be useful for increasing vertebral bone mass in postmenopausal women. Furthermore, the increase in coagulation function observed during this therapy was within the physiological range, and no adverse reactions were observed.

Autonomic nervous system activity in the late luteal phase of eumenorrheic women with premenstrual symptomatology.

The majority of women of reproductive age experience a regular recurrence of various symptoms in the premenstrual phase. The etiopathogenesis of premenstrual symptomatology, however, remains inconclusive. The present study was proposed to evaluate whether the activity of the autonomic nervous system (ANS), which largely contributes to the relative stability of a humans internal environment, is altered during the menstrual cycle of women with premenstrual symptomatology. Thirty eumenorrheic young women participated in this study. All subjects were investigated during the follicular and late luteal phases. The ANS activity was assessed by means of heart rate variability power spectral analysis during supine rest. No intramenstrual cycle differences in the ANS activity were found in women experiencing no or small increases in premenstrual symptoms. In contrast, the sympathetic nervous system (SNS) activity significantly increased and the parasympathetic nervous system (PNS) activity apparently decreased in the late luteal phase in subjects whose premenstrual symptomatology was not unbearable, but substantially increased (>20%) compared to the symptom-free follicular phase. The women with greater degrees of premenstrual distress possessed higher SNS activity and lower PNS activity in the late luteal phase than the women with less symptomatology. The ANS activity in the follicular phase did not differ among the subjects regardless of their premenstrual symptoms. Although causes and consequences continue to elude, the present study provides additional intriguing evidence that the altered functioning of ANS in the late luteal phase could be associated with diverse psychosomatic or behavioral symptoms appearing premenstrually.

Altered autonomic nervous system activity as a potential etiological factor of premenstrual syndrome and premenstrual dysphoric disorder.

BackgroundPremenstrual syndrome (PMS) encompasses a wide variety of cyclic and recurrent physical, emotional, and behavioral symptoms occurring during the late luteal phase of the menstrual cycle and abating shortly following the beginning of menses. Although PMS is widely recognized, its etiopathogenesis is not yet understood. The present study investigates whether the activity of the autonomic nervous system, which plays a vital role in orchestrating physiological homeostasis within the human body, is altered during the menstrual cycle of women with different degrees of premenstrual symptomatology.MethodsSixty-two women in their 20s to 40s with regular menstrual cycles participated in this study. All subjects were examined during the follicular and late luteal phases. Cycle phase was determined by the onset of menstruation and oral temperature and was verified by concentrations of ovarian hormones, estrone, and pregnanediol in a urine sample taken early in the morning. Autonomic nervous system activity was assessed by means of heart-rate variability (HRV) power spectral analysis during supine rest. The Menstrual Distress Questionnaire was used to evaluate physical, emotional, and behavioral symptoms accompanying the menstrual cycle of the subjects. The subjects were categorized in three groups, Control, PMS, and premenstrual dysphoric disorder (PMDD) groups, depending on the severity of premenstrual symptomatology.ResultsNo intramenstrual cycle difference in any of the parameters of HRV was found in the Control group, which had no or a small increase in premenstrual symptoms. In contrast, Total power and high frequency power, which reflect overall autonomic and parasympathetic nerve activity, respectively, significantly decreased in the late luteal phase from the follicular phase in the PMS group. As for the PMDD group, which had more severe symptoms premenstrually, heart-rate fluctuation as well as all components of the power spectrum of HRV were markedly decreased regardless of the menstrual cycle compared to those of the other two groups.ConclusionSeveral theories have been proposed to explain the underlying mechanisms of PMS with its complex web of bio-psycho-social factors. Although causes and consequences continue to elude, the present study provides intriguing and novel findings that the altered functioning of the autonomic nervous system in the late luteal phase could be associated with diverse psychosomatic and behavioral symptoms appearing premenstrually. In addition, when symptoms become more severe (as seen in women with PMDD), the sympathovagal function might be more depressed regardless of the menstrual cycle.

Prevalence, incidence, and awareness in the treatment of menopausal urinary incontinence.

OBJECTIVES To investigate the prevalence of urinary incontinence and to evaluate the awareness of treatment in postmenopausal women. METHODS The study group was comprised of 3026 postmenopausal women consulting the outpatient clinic. One component of the urological questions was formulated to determine the voiding habits and presence or absence of urinary incontinence. The incontinent responders were questioned further regarding the nature of the urine loss to determine the severity of incontinence. RESULTS It was reported by 26.3% (795/3026) of the respondents that they currently had urinary incontinence. They were classified by types as follows: stress 64.9%, urge 18.6%, and mixed incontinence 7.3%. The incidence of women who desired medical treatment for incontinence was only 2.9% (87/3026), while the incidence of women who actually received medical treatment for urinary incontinence was 1.9% (56/3026). CONCLUSIONS We conclude that urinary incontinence was prevalent to a significant extent among postmenopausal women, but that few affected individuals in this group consulted the medical center desiring clinical treatment. The present study demonstrated that it is necessary to improve the awareness of postmenopausal women concerning the benefits of seeking treatment for urinary incontinence, in order to improve their quality of life.

Endocrine Function of the Peri – and Postmenopausal Ovary

The concentration of sex steroids in peripheral and ovarian venous blood was measured in 130 perimenopausal women. We found that the postmenopausal ovary continues to secrete a large amount of testosterone and a moderate amount of androstenedione, estrone, and dehydroepiandrosterone. Although the mean estradiol levels in the ovarian vein of postmenopausal women was low, a few subjects showed estradiol levels higher than 50 pg/ml. Postmenopausal ovaries probably continue to secrete estradiol under some endocrine conditions. These data show that the postmenopausal ovary maintains some secretory function related to estrone and estradiol. However, the endocrine effect of the postmenopausal ovary may be related to its contribution of androgens to the plasma pool of estrogens through extragonadal conversion.

Changes in serum tumor necrosis factor (TNF-alpha) with kami-shoyo-san administration in depressed climacteric patients

An herbal medicine (kampo) is widely used to prevent or treat climacteric symptoms. In order to investigate the potential involvement of tumor necrosis factor (TNF)-alpha in susceptibility to mood disorder in climacteric women and to clarify the relationship between immune function and the efficacy of herbal medicine, we compared serum TNF-alpha levels in two treated groups, with and without concurrent use of herbal medicine. This study included 113 consecutive depressed menopausal patients who visited the gynecological and psychosomatic medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty-eight patients were administered kami-shoyo-san according to the definition of above sho. In contrast, 55 patients who were different in sho of kami-shoyo-san were administered antidepressants. Hamilton Rating Scale for depression (HAM-D) scores were determined at baseline and 12 weeks after starting treatment (endpoint). TNF-alpha concentrations were analyzed before and after 12 weeks of treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF-alpha after 12 weeks of treatment, to 17.22 +/- 6.13 pg/ml from a baseline level of 14.16 +/- 6.27 pg/ml (p = 0.048). The percent change in plasma concentration of TNF-alpha differed significantly between the kami-shoyo-san therapy group and the antidepressant therapy group at 4 weeks (12.0 +/- 7.8% and -1.22 +/- 0.25%, respectively, p < 0.01), 8 weeks (19.7 +/- 3.4% and -2.45 +/- 0.86%, respectively, p < 0.01), and 12 weeks (21.3 +/- 5.4% and -6.81 +/- 2.2%, respectively, p < 0.001). We found in this study that kami-shoyo-san, an herbal medicine, increased plasma TNF-alpha levels in depressed menopausal patients. Cytokines may play various roles in mood and emotional status via the central nervous system and may be regulated by herbal medicines, although the interactions are very complex.

Comparing the Effects of Estrogen and an Herbal Medicine on Peripheral Blood Flow in Post-menopausal Women with Hot Flashes: Hormone Replacement Therapy and Gui-Zhi-Fu-Ling-Wan, a Kampo Medicine

We investigated the association between blood flow in the extremities and hot flashes, and compared change in blood flow following hormone replacement therapy (HRT) and Gui-zhi-fu-ling-wan (Keishi-bukuryo-gan), a herbal therapy in post-menopausal women with hot flashes. Three hundred and fifty-two post-menopausal women aged 46-58 years (mean: 53.4 +/- 3.6 years) with climacteric complaints participated in the study. One hundred and thirty-one patients with hot flashes were treated with HRT (64 cases) or herbal therapy (67 cases). Blood flow was measured with laser doppler fluxmetry under the jaw, in the middle finger and in the third toe. Post-menopausal women with hot flashes (129 cases) showed significantly higher blood flow under the jaw (13.6 +/- 4.13) than women without hot flashes (166 cases) (5.48 +/- 0.84) (p < 0.0001). Blood flow at this site decreased significantly with either therapy (p < 0.0001). On the other hand, the administration of Gui-zhi-fu-lingwan significantly increased (p = 0.002) the blood flow in the lower extremities, whereas HRT decreased the blood flow. Thus, we have demonstrated that Gui-zhi-fu-ling-wan did not affect the activity of vasodilator neuropeptides on sensory neurons of systemic peripheral vessels uniformly. Therefore, Gui-zhi-fu-ling-wan, rather than HRT, is suggested as an appropriate therapy for treatment of hot flashes in the face and upper body with concomitant coldness in the lower body, which is one of the symptoms of menopause.

Efficacy of ipriflavone and 1α vitamin D therapy for the cessation of vertebral bone loss

Objective: This study investigated whether a combined regimen of ipriflavone and 1α vitamin D is effective in stopping postmenopausal bone loss. Methods: Ninety‐eight postmenopausal women were recruited and randomly assigned to one of four groups: group 1, ipriflavone alone; group 2, 1α vitamin D alone; group 3, combined regimen of ipriflavone and 1α vitamin D; group 4, no treatment. Vertebral bone mineral density, measured by dual energy X‐ray absorptiometry, serum alkaline phosphatase, calcitonin, parathyroid hormone, osteocalcin, urinary calcium and hydroxyproline were measured before and at the 6th, 12th and 18th month of the study. All comparisons were made using Students t‐test of means. Result: There was a significant reduction in vertebral bone loss in the patients receiving the combined therapy (mean loss after 18 months 0.33% in the combination group vs. 2.37%, 1.15% and 3.70% in the ipriflavone alone, 1α vitamin D alone, and control groups, respectively; P < 0.001). Conclusion: These findings suggest that the combined regimen could prevent postmenopausal bone loss.

Ciliary beat frequency controlled by oestradiol and progesterone during ovarian cycle in guinea‐pig Fallopian tube

The ciliary beat frequency (CBF) of guinea‐pig fimbria during the ovarian cycle was measured by video microscopy using a high‐speed camera (500 Hz). In the follicular phase, with increasing concentrations of β‐oestradiol ([βE2]) and a low concentration of progesterone ([PRG]), CBF increased from 13.5 to 16 Hz. In the ovulatory phase, with further increase of [βE2], CBF decreased gradually from 16 to 13.5 Hz. In the early luteal phase, with low [PRG] and [βE2], CBF increased to ∼17 Hz; however, in the middle luteal phase, with increasing [PRG], CBF decreased (∼12 Hz), and in the late luteal phase, with decreasing [PRG], CBF increased to ∼15 Hz. Then, in the resting phase, with low [βE2] and [PRG], CBF decreased immediately to ∼14 Hz. The CBF of the fimbria was measured in guinea‐pigs treated with β‐oestradiol benzoate (βE2B) or medroxyprogesterone (mPRG). A low dose of βE2B increased CBF to ∼14.5 Hz, whereas a high dose decreased it to ∼11 Hz. A βE2 receptor blocker, ICI‐182,780, abolished the βE2B‐induced CBF changes and maintained CBF at ∼12.0 Hz. Medroxyprogesterone decreased CBF to ∼12.5 Hz, and mifepristone (a PRG receptor blocker) abolished the mPRG‐induced CBF decrease and maintained CBF at ∼15 Hz. The addition of both blockers increased CBF to ∼18 Hz, suggesting that activation of βE2 or PRG receptors decreases the CBF of the fimbria. In conclusion, a moderate [βE2] increase maintains a high CBF (15.5 Hz) in the follicular phase, and then further [βE2] increase decreases CBF to 13.5 Hz in the ovulatory phase. In the early and late luteal phase, low [βE2] and [PRG] increase CBF to 17 and 15 Hz, respectively, and in the middle luteal phase a high [PRG] decreases CBF (to ∼12 Hz). Thus, the CBF of the fimbria was controlled by signals via βE2 and PRG receptors in guinea‐pigs.

Plasma lipid and lipoprotein levels in perimenopausal women : clinical research in 1198 Japanese women

Hyperlipidemia is associated with an increased prevalence of cardiovascular and cerebrovascular disease. We studied plasma lipid and lipoprotein levels with a survey of endocrine changes in the perimenopausal Japanese women.