Correlation of plasma microRNA-21 expression and bone turnover markers in postmenopausal women.

OBJECTIVES: This study assessed the correlation of plasma microRNA-21 expression and bone turnover markers (BTMs: CTx, P1NP) in healthy Thai postmenopausal women. We secondarily compared microRNA-21 expression between participants with normal and low bone mineral density (BMD: osteopenia and osteoporosis). METHODS: Postmenopausal women who had never been diagnosed with fracture or never used anti-osteoporosis drugs were included in this study. Baseline characteristics were collected from all 195 participants. BTMs and plasma miR-21-5p were analyzed from blood collection at 8:00 and 9:00 am after overnight fasting for at least 8 h. RESULTS: There was no significant correlation between miR-21-5p and any of the BTMs (CTx, r = 0.094, p = 0.19; P1NP, r = 0.05, p = 0.485). Significant correlation between miR-21-5p and P1NP was found when participants were further categorized into those aged ≥70 years (r = 0.46, p = 0.05) and those having osteoporosis (r = 0.51, p = 0.06). Slight negative correlations were found between miR-21-5p and BMD. There was statistically significant higher expression of miR-21-5p in those with low BMD when compared to the normal BMD group (p < 0.01). CONCLUSION: In this study, we did not find significant correlation between plasma microRNA-21-5p expression and the BTMs. Nevertheless, there seemed to be higher expression of miR-21-5p in the low BMD participants.

Effects of estrogen therapy on postmenopausal sleep quality regardless of vasomotor symptoms: a randomized trial.

OBJECTIVE: To determine the effects of estrogen therapy on objective sleep quality in insomniac postmenopausal women without severe vasomotor symptoms and/or recognized hot flushes during sleep. Study design Randomized, double-blinded, placebo-controlled trial, parallel design (ClinicalTrials.gov Identifier: NCT01501422). METHODS: Forty insomniac postmenopausal women with no severe vasomotor symptoms and/or recognized hot flushes during sleep were randomized into 2 months' treatment with a 50-µg transdermal estradiol patch or placebo. Sleep quality was determined objectively with wrist actigraphy. Sleep efficiency, total sleep time, wake up after sleep onset and number of awakenings were compared before and after treatment. The Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) questionnaires were used for subjective sleep quality assessment before and after treatment. RESULTS: The study showed no significant difference in sleep efficiency improvement between women having estrogen alone or placebo (median 85.7% vs. 85.2%, respectively, p = 0.71). Similarly, sleep quality scores assessed by ISI and ESS were not significantly different. CONCLUSION: Estrogen therapy in insomniac postmenopausal women without severe vasomotor symptoms and/or recognized hot flushes during sleep was not found to improve sleep efficiency during the study period.

Systemic effects of conjugated equine estrogen vaginal cream on bone turnover markers in postmenopausal women.

OBJECTIVE: To evaluate the systemic effect of therapy with conjugated equine estrogen (CEE) vaginal cream on bone turnover markers in postmenopausal women. METHODS: This study was conducted in 40 spontaneously menopausal women aged 40-60 years who complained of vulvovaginal symptoms. Subjects were instructed to self-administer 1 g CEE vaginal cream (CEE 0.625 mg) once daily for 12 weeks (continuous phase), then twice weekly for the next 12 consecutive weeks (intermittent phase). Serum levels of bone turnover markers and estradiol and the vaginal maturation index were evaluated at baseline, 12 and 24 weeks after treatment initiation. RESULTS: Levels of C-terminal cross-linked telopeptide of type I collagen (CTx) were significantly decreased at 12 weeks and 24 weeks when compared to baseline values (median (range) 0.435 (0.171-0.859) and 0.391 (0.122-0.714) vs. 0.562 (0.250-1.290) ng/ml (p < 0.001 and < 0.001), respectively), but there was no significant difference between the levels at 12 and 24 weeks. Levels of procollagen type I N-terminal propeptide (P1NP) and osteocalcin levels were significantly decreased after 24 weeks when compared to pretreatment levels (mean (standard deviation) 41.74 (11.76) vs. 50.02 (17.71) ng/ml (p = 0.002) for P1NP and 23.91 (7.11) vs. 27.54 (8.67) ng/ml (p < 0.001) for osteocalcin, respectively). Estradiol levels were significantly increased and the vaginal maturation index was significantly improved after 12 and 24 weeks when compared to baseline. CONCLUSIONS: CEE vaginal cream significantly decreased the bone resorption marker (CTx) in postmenopausal women after completion of the continuous-treatment phase. There was no significant further decrease after the intermittent phase. The effects on the markers of bone formation and bone turnover (P1NP and osteocalcin) were apparent only at 24 weeks. The two treatment phases moderately increased serum estradiol levels and significantly improved the vaginal maturation index.

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.

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.

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.

The effectiveness of hormone in relieving menopausal symptoms.

To assess the effectiveness of hormone replacement in relieving menopausal symptoms, 75 natural menopausal women suffering from these symptoms were recruited for this double-blind, placebo controlled study. These women were randomized into 2 groups. In the first eight weeks, the first group received a sequential regimen of Estradiol valerate 2 mg/day for 21 days and Norgestrel 0.5 mg/day from day 12 to 21, with seven days of drug-free interval, for two cycles. In the last eight weeks, placebo was given in the same fashion. In the second group, placebo was given in the first eight weeks, then hormone in the last eight weeks. The menopausal scores were recorded by the patients at weeks 0, 4, 8, 12 and 16. Sixty women completed the 16 week study, of which there were 30 women in each group. The mean menopausal score by eight weeks decreased significantly in the first group compared to the pretreatment value (The scores at week 0 and 8 = 20.03 and 12.63 respectively, p < 0.05). However, there was no significant change of the score in the second group. (The scores at week 0 and 8 = 21.20 and 19.43 respectively, p > 0.05). After switching from hormone to placebo in the first group, there was no significant change in mean menopausal score (The scores at week 8 and 16 = 12.63 and 13.73 respectively, p > 0.05). Nevertheless, when switching from placebo to hormone in the second group, the score decreased significantly. (The scores at week 8 and 16 = 19.43 and 13.20 respectively, p < 0.05). In conclusion, this study demonstrated the beneficial effects of hormone replacement in relieving menopausal symptoms.