The regulation of assisted reproductive technology in Thailand.

The Executive Board of the Medical Council of Thailand has set up an ad hoc committee to establish the regulations of practising of assisted reproductive technology. The committee assigned the Royal Thai College of Obstetricians and Gynecologists to supervise and take charge of the administration and formulate an annual report in accordance with the Thai Medical Council Declaration. The regulation was finally approved on October 9, 1997. It was announced in the Royal Gazette on December 26, 1997 and since then the prescription of standard measures for ART practice has been effected.

Difference in bone acquisition among hormonally treated postmenopausal women with normal and low bone mass.

This prospective analysis was conducted to compare the effects of hormone treatments on bone mineral density (BMD) of the lumbar spine, hip, and distal forearm in postmenopausal women with normal BMD and those with low bone mass. Eighty healthy women were randomly assigned to receive a cyclic regimen of standard hormone replacement therapy (HRT) or currently used low-dose oral contraceptive (OC). Women were categorized as normal BMD and low bone mass according to the Thai reference database. The results revealed that women with low bone mass gained more BMD than those with normal BMD. The difference in mean per cent bone acquisition was obvious at the spine. In addition, further subset analysis into OC and HRT groups revealed higher effects of OC on BMD when compared to HRT.

An effect of hormone replacement therapy on skin thickness in early postmenopausal women.

BACKGROUND: It is well known that dermal thickness, the major component of skin thickness, will decrease progressively after menopause. Bone and dermis share a similar organic constituent (collagen type I). The effect of hormone replacement therapy on bone has been established, whereas, its effects on skin are less well-described. This study was performed to determine the effect of combined estrogen-progestin replacement therapy in a sequential regimen on skin thickness in women during the early postmenopausal period. METHOD: One hundred early postmenopausal women who met the eligibility criteria and had already signed a consent form were non-randomly allocated in two groups. Group A; sixty women who received cyclic hormone replacement therapy in each 28-day cycle for 6 cycles. Group B; forty women who received 1,000 mg of calcium carbonate daily. Skin thickness was measured by ultrasonography before and after treatment and the Student's t-test was used to compare the results. RESULTS: A statistically significant increase in skin thickness over baseline was noted after combined estrogen-progestin replacement therapy had been administered for 24 weeks compared to the control and baseline groups. The skin thickness was also significantly decreased after calcium had been administered for 24 weeks when compared to baseline. CONCLUSION: Skin thickness was increased in early postmenopausal women subjected to hormone replacement therapy with an alternating dose of estrogen and progestin.

Pipelle versus fractional curettage for the endometrial sampling in postmenopausal women.

The experimental and cross over design study was performed to compare the pain, ability to sample the endometrial issue, and pathological results from pipelle and fractional curettage in post menopausal patients. Thirty naturally menopausal patients who visited King Chulalongkorn Memorial Hospital with abnormal bleeding per vagina from June 1 to December 31, 1997, were enrolled in the study. In group A,endometrial tissue sampling was first conducted by Pipelle and followed by fractional curettage. In group B, the fractional curettage was performed before Pipelle. The results showed that the pain derived by the visual analogue scale of Pipelle and fractional curettage were 3.34 +/- 1.44 (mean +/- SD) and 6.58 +/- 1.75 respectively (p<0.01). The sensitivity and specificity of Pipelle in endometrial tissue samplings compared with fractional curettage were 87.5 and 100 per cent, respectively. One from 3 cases of adeneocarcinoma of the endometrium could not be detected by Pipelle. In conclusion, Pipelle significantly produced less pain than fractional curettage. Even though Pipelle is a simple and easy method for endometrium sampling, the use of Pipelle to replace fractional curettage in the management of postmenopausal bleeding should be done with caution. False negative could occur in the focal disease of malignancy of the endometrium.

Diagnostic hysteroscopy at King Chulalongkorn Memorial Hospital: 7 years experience.

We reported our experience and results of diagnostic hysteroscopy performed on 294 patients between June 1994 and May 2000 at the Gynecologic Endoscopy Unit, King Chulalongkorn Memorial Hospital. Diagnostic hysteroscopy was performed successfully in 286 patients (97.3%), allowing thorough inspection of the uterine cavity. Cervical dilatation was required in 146 patients (49.6%). The most common indication was endometrial polyps (34.4%) followed by infertility (19.4%) and abnormal uterine bleeding (14.9%), respectively. Each of the hysteroscopic findings accounted for 103 patients (35%) in endometrial polyps and normal endometrium. The procedure failed in 8 patients (2.71%) due to uterine perforation. In conclusion, diagnostic hysteroscopy should be considered as a safe, effective and successful investigation procedure for suspected intrauterine pathology.

Accuracy of hysteroscopic diagnosis of endometrial polyps.

OBJECTIVE: To evaluate the diagnostic accuracy of endometrial polyps by hysteroscopy. MATERIAL AND METHOD: One hundred and sixty five women undergoing diagnostic hysteroscopy between January 1996 and December 1998 at the Gynecologic Endoscopy Unit, King Chulalongkorn Memorial Hospital were recruited in this study. The hysteroscopic diagnosis was compared with the histopathology by endometrial curettages performed after hysteroscopy. RESULTS: Endometrial polyps were diagnosed by hysteroscopy in 54 patients (32.73%). When compared to tissue pathology, we found an accuracy of 81.21 per cent, sensitivity of 92.59 per cent, specificity of 78.98 per cent, positive predictive value of 46.29 per cent, negative predictive value of 98.19 per cent, false positive of 17.57 per cent and false negative of 1.21 per cent. CONCLUSION: For endometrial polyps, diagnostic hysteroscopy yields a high accuracy but low positive predictive value. Therefore, endometrial biopsy is necessary to confirm diagnosis of endometrial polyps by hysteroscopy.

The metabolic and bone density effects of continuous combined 17-beta estradiol and noresthisterone acetate treatments in Thai postmenopausal women: a double-blind placebo-controlled trial.

OBJECTIVE: To compare the changes of lipid parameters, liver function tests, fasting plasma glucose and bone density in Thai postmenopausal women who received this combined hormonal treatment and placebo. STUDY DESIGN: Double-blinded, randomized controlled trial study. MATERIAL AND METHOD: Sixty postmenopausal women attending the menopause clinic at Chulalongkorn Hospital from July, 1996 to December, 1996, were enrolled in the study. The patients were randomized to receive the placebo or drug (17 beta-estradiol 2 mg and norethisterone acetate 1 mg) continuously. Patient characteristics, physical examination, liver function tests, fasting plasma glucose, lipid parameters (fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL) and triglyceride level) and bone densitometry were performed before beginning the study. The lipid parameters were repeated at 3, 6 and 12 months. Fasting plasma glucose, liver function tests and bone densitometry were repeated at 12 months. RESULTS: In the drug group, there were significant changes in the cholesterol at 3, 6 and 12 months when compared to the baseline. There were significant differences at 3, 6 and 12 months when compared between groups. The HDL values were not significantly different within groups. The LDL values at 3, 6, 12 months were significantly lower than the baseline in the drug group when compared within groups and at 6, 12 months in the placebo group. The triglyceride values were not significantly different between groups and within groups. There was no significant change between groups and within groups of fasting plasma glucose, total bilirubin, direct bilirubin, AST, ALT, albumin and globulin. The alkaline phosphatase values were significantly decreased at 12 months in the drug group. The bone density of total BMD and T-score at the spine of the drug group increased significantly at 12 months. The per cent change per year was +5.1. In contrast, the values in the placebo group decreased significantly, the per cent change per year was -0.9. The same pattern was also found in the bone density of the total hip. But when focused to the femoral neck, we found no significant change in both groups. CONCLUSION: This continuous combined treatment resulted in beneficial changes of bone density and lipid profiles. The therapy prevented bone loss and the changes in serum lipoprotein were concordant with a lipid profile associated with a decreased risk of coronary heart disease in Thai postmenopausal women.

Bone mineral density of lumbar spine and proximal femur in normal Thai women.

OBJECTIVE: To find the reference data for age-specific normal bone mineral density in a Thai female population. STUDY DESIGN: Cross-sectional, Descriptive study. MATERIAL AND METHOD: 1773 Thai women aged between 11-80 years were recruited, using multistage cluster sampling and stratifying from six represented provinces in the country, each strata was randomly selected. After recruiting, the women were interviewed by well-trained personnel using structured questionnaires. Bone mineral density of the lumbar spine 1-4 and nondominant hip were measured by Dual Energy Photon Absorptiometer. The scientists, X-rays technician were trained and standardized inter and intra observers variation. Quality control of examination was measured periodically. Every BMD outcome was re-examined by a specialist. RESULTS: The peak bone mineral density of both spines and hips was between the age of 30 to 34 years old. Mean Value for spine and femoral neck was 0.957 and 0.814 g/cm2 respectively. The BMD of spine and hip was significantly decreased after the age of 35 and the loss was accelerated at age 50. Osteoporosis for spine and femoral neck is considered when BMD are below 0.682 and 0.569 g/cm2 respectively. CONCLUSION: The results are important data for public health policy, by maximizing bone mass during skeletal growth before menopause and minimizing bone loss throughout life as well as for detection of important risk factors.

Comparison of norgestrel- versus cyproterone acetate-containing hormone replacement therapy on lipid-lipoprotein metabolism.

To compare the effects on the lipid profile of estradiol valerate with norgestrel to a regimen of estradiol valerate with cyproterone acetate. Sixty-four healthy women in their perimenopause or early postmenopause, aged between 40-55 years, were randomized to one of the two 21-day sequential regimens: estradiol valerate 2 mg/day for 21 days and combined with either norgestrel 0.5 mg/day or cyproterone acetate 1 mg/day from day 12 to 21, with 7 days of drug-free interval, for 12 cycles. Lipid profiles were followed at baseline, 6 and 12 cycles. Sixty-one subjects completed the study, 30 in the norgestrel group and 31 in the cyproterone group. During 12 cycles of study, serum HDL cholesterol levels decreased significantly in the norgestrel group (p < 0.01) and were unchanged in the cyproterone group. The levels were significantly lower in the norgestrel group than in the cyproterone group (p < 0.05). No differences were found between groups as regards LDL cholesterol and total cholesterol levels. Triglyceride levels decreased significantly in the norgestrel group (p < 0.01), remained unchanged in the cyproterone group and the levels were significantly different between groups (p < 0.01). In conclusion, the study demonstrated that sequential regimen of estradiol valerate with norgestrel produced less favorable HDL cholesterol but more favorable triglyceride levels than the regimen of estradiol valerate with cyproterone acetate.

Uterine blood flow response to hormonal replacement therapy in asymptomatic postmenopausal women: a transvaginal Doppler study.

To evaluate the effect of continuous hormonal replacement therapy (HRT) on Doppler parameters of uterine blood flow in asymptomatic postmenopausal women. Thirty-eight asymptomatic postmenopausal women were recruited into the study from the outpatient menopause clinic, Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University. The study population was divided into 20 cases without any HRT (group 1) and 18 cases using continuous conjugated equine estrogen 0.625 mg/day combined with medroxyprogesterone acetate 2.5 mg/day (group 2). The duration of HRT was 21.3 +/- 9.5 (13-56) months. A transvaginal colour flow imaging system (ALOKA SSD-2000 MultiView, Tokyo, Japan) was used to assess uterine blood flow. Quantitative data from areas of colour were evaluated by pulsed Doppler spectrum analysis. Resistance indices (RI) were measured as indicators of uterine perfusion. Both groups were statistically similar with respect to age, parity, age at menopause, height and weight. The endometrial thickness in group 1 and 2 were 3.8 +/- 0.8 and 4.1 +/- 0.6 millimetres, respectively. The left uterine artery RIs of group 1 and 2 were 0.86 +/- 0.08 and 0.84 +/- 0.07, respectively (p = 0.33). The right uterine artery RIs of group 1 and 2 were 0.87 +/- 0.07 and 0.83 +/- 0.06, respectively (p = 0.06). In conclusion, continuous HRT had a non-significant influence on uterine blood flow in the postmenopausal women.

Clinical effects of 17 beta-estradiol and norethisterone acetate in postmenopausal Thai women.

OBJECTIVE: To compare the climacteric symptoms, the bleeding patterns, side effects, endometrial thickness, serum follicular stimulating hormone (FSH) and estradiol level in postmenopause Thai women who received this drug and placebo. STUDY DESIGN: Double blind, randomized placebo controlled trial. MATERIAL AND METHOD: Sixty postmenopausal women attending the menopause clinic at Chulalongkorn Hospital from July, 1996 to December, 1996, were enrolled in the study. The patients were randomized to receive the placebo or drug (17 beta-estradiol 2 mg and norethisterone acetate 1 mg) continuously. After 12 months, 13 patients in the drug group were switched to have placebo and 13 patients in the placebo were switched to the drug group. Recording of patient characteristics, physical and gynecologic examination, pap smear, breast examination and mammogram, climacteric symptom scores, transvaginal ultrasonography, serum FSH and Estradiol level were performed prior to the study. Physical examinations, breast palpitations, measurement of body weight and blood pressure, climacteric symptom scores and side effects were repeated at 3, 6, 12, 18 months. Gynecologic examination, pap smear, serum FSH and estradiol, transvaginal ultrasonography, were repeated at 12 months. RESULTS: The women in the drug group had fewer climacteric symptoms than baseline after 6 months. The incidence of amenorrhea was 74.0 per cent at 12 months. The incidence of abnormal uterine bleeding (spotting and breakthrough bleeding) was 37.0 per cent at 3 months, 29.6 per cent at 6 months, 25.9 per cent at 12 months and 7.1 per cent at 18 months. The women in the drug group had fewer climacteric symptoms than baseline after 6 months. Breast tenderness was the most common side effect. The endometrial thickness decreased significantly in the drug group. Serum FSH decreased and serum estradiol increased significantly in the drug group. CONCLUSION: This combined regimen was more effective in relieving the climacteric symptoms in women who used the drug than those who used the placebo. There was a high incidence of amennorhoea after 12 months. But there was also a high frequency of abnormal bleeding in the first 3 months of treatment. Counseling on the bleeding pattern and common side effects should be conducted before starting the treatment to increase the compliance. This combined regimen proved to be a useful alternative for postmenopausal Thai women who prefer to avoid cyclic bleeding from sequential therapy.

Dyslipidemia among healthy postmenopausal Thai women.

A prospective analysis was conducted to assess the prevalence of dyslipidemia among 80 healthy postmenopausal Thai women who were not more than five years after menopause. Serum total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol were measured using enzymatic procedures. Low-density lipoprotein (LDL) cholesterol concentration was estimated by Friedewald formula. The results showed that 91.25 per cent, 10.00 per cent, 38.75 per cent and 48.75 per cent of the studied population had total cholesterol > or = 200 mg/dl, triglycerides > or = 150 mg/dl, HDL < 50 mg/dl, and LDL > or = 190 mg/dl respectively. Of all the women, 77.50 per cent and 10.00 per cent had total cholesterol / HDL ratio of > or = 4 and had triglyceride levels of > or = 150 mg/dl with HDL < 50 mg/dl, respectively. This unexpected high prevalence of dyslipidemia in this healthy postmenopausal group should be taken into account in considering health promotion strategies for postmenopausal Thai women particularly those in the high risk group.

The predictive value of skin thickness in the diagnosis of osteopenia.

Skin and bone share a similar organic constituent (type I collagen) which decreases with time after menopause due to hypoestrogenism. The interdependence of skin and bone atrophy has been reported. This study was conducted to assess the predictive value of an ultrasonographic measurement of skin thickness in the diagnosis of osteopenia (BMD below -1.5 SD.) in perimenopausal and early postmenopausal women. All patients had skin thickness measured by the same radiologist and had a dual-energy X-ray absorptiometry (DEXA) scan of the lumbar spine and the femoral neck. Of the 77 women studied, the mean age was 50.9 +/- 3.0 years. Thirty patients were in perimenopause and 47 in early postmenopause. Mean skin thickness was 2.1 +/- 0.4 mm. Women with a skin thickness of < or = 1.7 mm carried a higher risk for developing osteopenia at the lumbar spine (odds ratio 8.41, 95% confidence interval 2.19-32.35) and the femoral neck (odds ratio 3.88, 95% CI 1.14-13.17). Patients with a skin thickness of > or = 2.4 mm had a lower probability of osteopenia at the lumbar spines (odds ratio 0.17, 95% CI 0.035-0.845) and the femoral neck (odds ratio 0.22, 95% CI 0.055-0.899). In conclusion, a low skin thickness measurement by ultrasonography may be used as an indicator for osteopenia in perimenopausal and early postmenopausal women.

Skin thickness in different menopausal status.

It is well known that skin thickness will decrease in the years after menopause. Women may have climacteric symptoms including those associated with skin alterations as early as during the perimenopausal period. This study was performed to compare the skin thickness of women in their premenopause (N = 31), perimenopause (N = 35) and early postmenopause (N = 46). The mean skin thickness in each group was 2.28 +/- 0.39 mm., 2.18 +/- 0.35 mm. and 2.02 +/- 0.36 mm. respectively. The skin thickness of women in the early postmenopausal group was significantly lower than those in the premenopausal group, but no difference was found between premenopausal and perimenopausal group nor between perimenopausal and early postmenopausal group. Furthermore, we found no correlation between skin thickness and chronological age. In conclusion, the decline in skin thickness of women entering menopause requires a period of time to undergo significant alterations and the study revealed a significant reduction of skin thickness as early as in the course of the early postmenopausal period.

Estradiol and follicle-stimulating hormone levels in oophorectomized women applying percutaneous 17 beta-estradiol over the medial surface of the left arm.

To assess the changing estradiol (E2) and follicle stimulating hormone (FSH) level in oophorectomized women applying percutaneous 17 beta estradiol over the medial surface of the left arm. Thirty-nine women, who had undergone total abdominal hysterectomy and bilateral oophorectomy after 4 weeks, were enrolled into the study. All subjects received a daily dose of 1.5 mg percutaneous 17 beta-estradiol in 2.5 g of the gel, applied over the medial surface of the left arm in the limited area of 150 cm2. Serum E2 and FSH were measured before and after commencing the study at weeks 4, 8 and 12. The measurement was performed 12-14 hours after the gel application, using time-resolved fluoroimmunoassay (FIA) method. Serum E2 significantly increased from the baseline value at weeks 4, 8 and 12 (Median of E2 value at weeks 0, 4, 8 and 12 = 47.30, 86.78, 128.00 and 163.15 pmol/L, respectively, P < 0.05). While the serum FSH level significantly decreased. (Median of FSH value at weeks 0, 4, 8 and 12 = 66.05, 60.40, 53.35 and 48.40 IU/L, respectively, P < 0.05). In conclusion, this dose, duration and route of estrogen administration increased the serum E2 level close to the early to mid-follicular phase of the normal menstrual cycle. While FSH level significantly decreased but did not reach the premenopausal range.

Postmenopausal osteoporosis: what is the real magnitude of the problem in the Thai population?

To assess the prevalence of osteoporosis, bone mass measurement was performed on 1,047 women attending a menopause clinic at Chulalongkorn Hospital, Bangkok. The mean age of the population was 50.5 +/- 5.7 years. The bone density was measured at lumbar spines (LS) (L1-L4) and the non-dominant femoral neck (FN) site utilizing a Hologic QDR 2000 dual energy X-ray absorptiometer. According to the World Health Organization's (WHO) definition a value of bone mineral density (BMD) that is more than 2.5 standard deviation (SD) below the young adult mean is considered diagnostic of osteoporosis. In this study, Thai and American cut-off values of BMD for osteoporosis were used to compare the prevalence of osteoporosis. Using Thai's cutoff value, the results showed a lower prevalence of osteoporosis of both LS and FN (15.7% and 9.5%, respectively). Considering the subgroups of the studied population, the prevalence of osteoporosis of LS and FN utilizing Thai's cutoff value was significantly higher in postmenopausal than in premenopausal women. (Premenopause vs postmenopause, LS: 4.7% vs 21.4%; FN: 4.7% vs 11.9%, respectively, P < 0.05) WHO's definition of osteoporosis (the cutoff value of 2.5 SD below the young adult mean) is based on the rationale that this cutoff value identifies approximately 30 per cent of postmenopausal white women as having osteoporosis which is approximately equivalent to the lifetime risk of fracture at the spine, hip and forearm of white women at age 50 years. The prevalence of osteoporosis obtained in this study might not represent the true magnitude of the problem in Thailand. Until we have our own lifetime fracture risk which will enable us to have an appropriate cutoff value to diagnose osteoporosis, this prevalence might be used as an approximate figure or initial information for further research in this field.

Similarity of bone mass measurement among hip, spines and distal forearm.

From January-December 1995, bone mineral density (BMD) of lumbar spine, hip and distal forearm were studied in 325 healthy women visiting the menopause clinic, Chulalongkorn Hospital. This retrospective analysis was conducted to assess the correlation of BMD among various measurement sites. Bone mass measurement at hip and spine were performed utilizing dual energy X-ray absorptiometer (DEXA), Hologic QDR 2000 and at distal forearm by single energy X-ray absorptiometer (SEXA), Hologic DTX 100. By canoconical correlation, the results revealed a significant correlation of BMD of distal and ultra-distal part of forearm with various sites of hip (r = 0.602, p < 0.001). There was also significant correlation of distal and ultra-distal part of forearm with various sites of spines (r = 0.619, p < 0.001). Though there is some heterogeneity of bone mass density among different measurement sites, practically with this fairly good level of correlation, bone mass measurement of distal forearm might be used to predict the BMD of hip and spine in Thai women. The accuracy of predicting the BMD of hip and spine by BMD of distal forearm in the mass screening programme in Thailand is now going on. The results will be followed.

Estradiol and follicle-stimulating hormone levels in oophorectomized women using vaginal estrogen.

To assess the changing estradiol (E2) and follicle-stimulating hormone (FSH) level in oophorectomized women using vaginal estrogen. Serum estradiol and FSH were evaluated in 32 oophorectomized women using a daily dose of 2 g base of 1.25 mg vaginal conjugated equine estrogen (CEE) cream. The blood sample for hormone assay was collected 8-10 hours from the time of vaginal application. E2 and FSH levels were measured in the serum sample before and after commencing the study at 4, 8 and 12 weeks using the time-resolved fluoroimmunoassay method. Serum estradiol significantly increased from baseline value at 4, 8 and 12 weeks. (Mean +/- SD of E2 value at 0, 4, 8, 12 weeks: 9.97 +/- 12.13, 249.83 +/- 170.46, 299.38 +/- 190.65, 322.82 +/- 218.31 pmol/L, respectively, P < 0.05) On the other hand, serum FSH significantly decreased from baseline value at 4, 8 and 12 weeks. (Mean +/- SD of FSH value at 0, 4, 8, 12 weeks: 77.64 +/- 27.24, 40.33 +/- 21.64, 38.84 +/- 22.33, 30.90 +/- 24.32 IU/L, respectively, P < 0.05) In conclusion, a daily dose of 2 g vaginal CEE cream raised the serum estradiol level close to the normal level in the follicular phase of the normal menstrual cycle. However, even though FSH significantly decreased it did not reach the premenopausal level.

Bone loss in oophorectomized Thai women.

This prospective analysis was done in 95 postmenopausal women to observe bone loss rate between 59 natural and 36 surgical menopausal women with or without hormonal replacement therapy (HRT). Bone mass measurement was performed at lumbar spines (L1-L4) and hip by dual energy X-ray absorptiometer at 0, 6 and 12 months. The results revealed that in the non-HRT group there was significant faster bone loss rate of lumbar spines (LS) and hip (H) of the surgical group at 12 months (Natural group: LS = -1.11%, H = +2.38%; Surgical group: LS = -4.51%, H = -0.66%, P < 0.05). However, there was no significant difference in bone changes of lumbar spines and hip between natural and surgical group with HRT at 12 months (Natural: LS = +2.0%, H = +4.06%; Surgical: LS = +0.62%, H = +2.28%, P > 0.05). This observation showed that without HRT oophorectomized women had greater magnitude of bone loss than women who entered menopause naturally.

Correlation of bone mineral density among various measurement sites.

Bone mineral density (BMD) of the lumbar spine and hip was studied in 1,047 women visiting the menopause clinic, to assess the correlation of BMD among various measurement sites. Bone mass measurement was performed utilizing dual energy X-ray absorptiometer (DEXA), Hologic QDR 2000. The results revealed a significantly high correlation of BMD of total hip and spine. (r = 0.7021, P < 0.001) Nevertheless, BMD of the spine was mostly correlated with BMD of trochanteric site (r = 0.7235, P < 0.001) and least correlated with BMD of intertrochanteric region. (r = 0.2426, P < 0.001) In conclusion, BMD of spine and hip is highly correlated. However, there was some heterogeneity of correlation in different specific measurement sites.