Beneficial aspect of oral estriol as hormone replacement therapy: consideration on bone and lipid metabolism.

To improve the quality of life of elderly people in Japanese society where women have the longest life expectancy in the world, osteoporosis, and hyperlipidemia are among the major targets of medical treatment. To differentiate two types of regimens for hormone replacement therapy (HRT), we tried to evaluate the efficacy on lipid and bone metabolism. With informed consent, 34 postmenopausal women of more than 2 years were assigned to receive 1 of 2 types of HRT (the HRT group) for 12 months observation: one with a combination of conjugated equine estrogen (CEE) 0.625 mg/day and medroxyprogesterone acetate (MPA) 2.5 mg/day (the CEE group), and the other with oral estriol (E3) 2 mg/day (the E3 group). Parameters of serum lipid were measured, as well as those of bone metabolism with bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) using QDR-2000. In HRT groups, lipid and bone metabolism were confirmed to be improved. Whereas, an increase of triglycerides (TG) observed in the CEE group was not observed in the E3 group. Thus, in the clinical management of postmenopausal women, oral E3 preparation as an alternative regimen for HRT for CEE might be efficacious.

Common carotid artery stiffness, cardiovascular function and lipid metabolism after menopause.

While cardiovascular disease is a major cause of death in elderly women, relatively little is known regarding the influence of menopause on atherogenesis. We tried to characterize postmenopausal changes in the arterial properties. A group of 72 postmenopausal women were classified into subgroups based on duration of the postmenopausal period (PMP): Group PM1 (1-2 years; n = 16), PM4 (2-6 years; n = 16), PM8 (6-10 years; n = 25), and PM12 (10-15 years; n = 15). The control group consisted of 24 volunteers with regular menstruation (PM0). The diameter pulse waveform and intima-media thickness (IMT) of the common carotid artery (CCA) was measured using a phase-locked echo tracking system coupled with B-mode ultrasonography. The stiffness index was calculated from the waveform and the systemic blood pressure. The cardiac contractile force and the cerebral perfusion were also estimated using the maximum incremental velocity (MIV) and the calculated blood flow, as well as the fasting lipid profile. When compared to control, significant and progressive increases were noted in total cholesterol and low density lipoprotein (PM1, PM4, PM8, PM12), IMT (PM8, PM12), and SI (PM1, PM4, PM8, PM12). Further significant and progressive reductions were noted in pulse amplitude of CCA diameter (PM1, PM4, PM8, PM12) and MIV and cerebral perfusion (PM8, PM12). The postmenopausal increase in CCA stiffness as well as lipid profile occurs earlier than the increase in IMT and may be a more sensitive predictor of disorder on arterial property.

Anesthesia and acoustic stress-induced intra-uterine growth retardation in mice.

Stress interferes with reproduction, adversely influencing implantation and fetal growth, and sometimes even leading to abortion. Here, we attempted to evaluate the early gestational effects of uncomfortable sound on pregnant mice and their offspring. Ten-week-old pregnant Jcl:ICR mice were exposed to sound (100 dB, random frequency between 9-34 kHz) for 8 hours on the 3(rd), 5(th) and 7(th) gestational days (GD). The effects of general anesthesia were also investigated, with or without acoustic stress. All groups were examined on the 18(th) GD for fetal growth. Fetal weight, number of ossified sacrococcygeal vertebrae and placental weight were all significantly reduced (P<0.0001) when stress was induced on the 7(th) GD, but not on the 3(rd) or 5(th) GD. This intra-uterine growth retardation (IUGR) was significantly inhibited by general anesthesia (P<0.0001), although general anesthesia alone induced significant IUGR (P<0.0001) when compared with control mice. This suggests that acoustic exposure indirectly exerts an effect on fetal growth, possibly via a psycho-maternal pathway. We also found that analysis of the number of ossified sacrococcygeal vertebrae is the most sensitive tool for the study of IUGR.

Preservation of tubal function following methotrexate treatment for ectopic pregnancy.

To evaluate methotrexate (MTX) administration as a conservative treatment for ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of MTX treatment for tubal pregnancies at our department between December 1985 and December 2003, and compared its pregnancy prognosis with that of laparoscopic salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 % and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively, after the salpigotomy. These results suggest that MTX treatment is comparable to the more conservative operation. To clarify the (dys/) function of the ectopic implantation tubes and MTX-treated tube (s), we excluded patients who had a contra-lateral healthy tube, and extracted 40 patients as "the affected tube group", where the pregnancy-related parameters were not adversely affected. The findings suggest that MTX is not necessary to preserve tubal function.

Impact of menopause on lipid and bone metabolism and effect of hormone replacement therapy.

BACKGROUND: Hyperlipidemia and osteoporosis are the medical targets to improve the quality of life of increasing elderly women. OBJECTIVE: To elucidate the effect of menopause and hormone replacement therapy (HRT) on lipid and bone metabolism. SUBJECTS: With their written informed consent, studied were 89 postmenopausal with 30 premenopausal women, and postmenopausal 35 were assigned into HRT (n = 18) or control group (n = 17); the former received conjugated equine estrogen (0.625 mg/day) and medroxyprogesterone acetate (2.5 mg/day), the latter calcium aspartate (800 mg/day). OUTCOME MEASURED: Parameters were measured for lipids; total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), triglycerides (TG), lipoproteins, and apolipoproteins as well as for bone metabolism; parathyroid hormone (PTH), 1,25(OH)2D3, bone type of alkaline phosphatase (b-ALP), intact bone gla protein (I-BGP), tartrate-resistant acid phosphatase (TRAP) in serum. Bone mineral density (BMD) of lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). Two atherogenic indices (AIs) were calculated: AIc equals [TC - HDLC]/HDLC, and AIap equals (apolipoprotein B)/(apolipoprotein A1). RESULTS: TC increased in approximately 10% within 2 years after menopause with increased LDLC (approximately 20%) and decreased HDLC (approximately 10%), and atherogenic indices were both elevated. In HRT, HDLC increased, while TC and LDLC and TG showed no significant change; lumbar BMD increased by 3% after 12 month, while bone formation markers decreased; PTH increased and 1,25(OH)2D3 decreased. CONCLUSION: We provided the natural changes of lipid and bone metabolism after menopause and how extent an estrogen replacement can reset these changes.