Determinants of attained estradiol levels in response to oral estradiol plus progesterone therapy.

OBJECTIVES: Among postmenopausal women taking hormone therapy (HT), the estradiol (E2) dose and E2 levels were differentially associated with change in metabolic measures. We evaluated determinants of attained E2 levels in response to HT. METHODS: Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models assessed characteristics associated with E2 levels among women with ≥80% HT compliance, adjusted for E2 dose and baseline E2 level. RESULTS: Among 1173 postmenopausal women with mean (standard deviation) age 55 (4.3) years and 5.2 (4.8) years since menopause, higher treated E2 levels were significantly related to younger age, more recent menopause, and current alcohol use, while lower E2 levels were related to current smoking. Both age and time since menopause were significantly inversely associated with E2 levels; time since menopause had a stronger association with E2 levels. In the final multivariable model, E2 levels were positively associated with current alcohol use, and inversely associated with time since menopause and current smoking. CONCLUSION: Adjusting for E2 dose and baseline E2 level, on-trial E2 levels were significantly associated with time since menopause, current smoking, and current alcohol use. Practitioners should consider these factors in individual women to achieve a desirable E2 level during HT.

Association of oral estradiol dose/levels with coagulation measures in early/late postmenopausal women.

Objective: This study evaluated associations of estradiol (E2) dose and serum E2 levels with coagulation/anti-coagulation measures in early (<6 years) compared with late (≥10 years) postmenopausal women.Methods: Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models tested the association of E2 dose and serum E2 levels with the prothrombin time (PT), the activated partial thromboplastin time (APTT), antithrombin (ATHRM), fibrinogen (FIBRINO), protein C (PROTC), and protein S (PROTS), assessed five times over 12 months.Results: Among 1215 early and 297 late postmenopausal women, the E2 dose was statistically significantly inversely associated with the APTT in early postmenopause, PROTC in late postmenopause, and with the PT, ATHRM, and PROTS in both groups. Serum E2 levels were statistically significantly inversely associated with the APTT, PROTS, and FIBRINO in early postmenopause, the PT in late postmenopause, and ATHRM and PROTC in both groups. With longer time since menopause, the inverse E2 dose effect and serum E2 effects became stronger.Conclusion: Increasing E2 dose and serum E2 levels were associated with changes in coagulation/anti-coagulation measures. The associations were stronger among women ≥10 years since menopause when initiating E2. The timing of E2 therapy, E2 dose, and serum E2 levels relative to time since menopause may modify the venous thromboembolism risk.

A pilot study: estradiol/progesterone effect on cervico-vaginal cytokines in premenopause and postmenopause.

Objective: We compared cervico-vaginal cytokines in hormone therapy (HT)-treated postmenopausal women with premenopausal women and explored the association of serum estradiol (E2) and progesterone (P4) with cervico-vaginal cytokines.Methods: Postmenopausal women were treated with oral E2 1 mg/day for 28 days, with oral P4 100 mg/day added for the last 14 days. Premenopausal women were evaluated over one menstrual cycle. Serum E2 and P4 levels and cervico-vaginal cytokines interleukin (IL)-8 and IL-1ß were measured at baseline, 14 days, and 28 days and were estimated by specific enzyme-linked immunosorbent assays.Results: Among nine postmenopausal and seven premenopausal women, cervico-vaginal IL-8 levels were highest at baseline, decreased on day 14, and remained stable thereafter. Cervico-vaginal IL-1ß levels were highest at baseline, decreased on day 14, and remained stable with HT in postmenopausal women while they increased in premenopausal women. Postmenopausal women treated with HT and premenopausal women had similar changes in IL-8 and IL-1ß. Serum E2 levels negatively correlated with IL-8 and IL-1ß levels. Increased serum E2 from HT was correlated with the decreased IL-8 level from baseline to day 14 (p = 0.03).Conclusion: Exogenous E2 and P4 decreased the cervico-vaginal IL-1ß and IL-8 to those levels found in premenopausal women. These findings require confirmation in a larger prospective study.

Circulating androgen levels before and after oophorectomy in premenopausal and postmenopausal women.

OBJECTIVE: This study aimed to determine the effect of oophorectomy on baseline serum levels of androgens and estrogens in premenopausal and postmenopausal women. METHODS: Fourteen premenopausal and 10 postmenopausal women underwent total hysterectomy and bilateral oophorectomy for benign disease of the uterus. Serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17ß-diol-17ß-glucuronide (3α-diol G), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by highly specific immunoassays prior to surgery and 2 weeks afterward. Free T and free E2 were calculated. Differences were determined between preoperative (preop) and postoperative (postop) samples, and between premenopausal and postmenopausal women. RESULTS: In premenopausal women, postop levels of total and free T, DHT, and total and free E2 decreased significantly from preop. Postop levels of DHEAS, A, 3α-diol G, and SHBG were decreased, but not significantly different from preop. In postmenopausal women, postop levels of total and free T and total and free E2 decreased significantly from preop, but there was little change in the other compounds. Significant differences in the mean change from baseline between premenopausal and postmenopausal women were observed only for E1 and total and free E2. CONCLUSION: The significant decrease in serum T in postmenopausal women following oophorectomy adds to the evidence that the postmenopausal ovary continues to produce T.

An International Menopause Society study of vasomotor symptoms in Bangkok and Chiang Mai, Thailand.

OBJECTIVES: To examine relationships between location, demographics, lifestyle, beliefs, and experience of hot flushes and night sweats (HFNS) amongst women living in two cities in Thailand. METHODS: Cross-sectional study of peri- and postmenopausal women, aged 45-55 years, from Bangkok and Chiang Mai. Participants completed questionnaires (demographics, health, HFNS (prevalence, frequency and problem-rating) and beliefs about menopause). A sub-sample of women from each location was interviewed. RESULTS: A total of 632 women (320 Bangkok and 312 Chiang Mai) aged 50.88 (standard deviation 3.06) years, took part. The prevalence of HFNS was 65%, average HFNS frequency 8.7 (10.8) per week and problem rating 4.3/10. Women from Chiang Mai had significantly more problematic HFNS, but prevalence and frequency were similar in both sites. Poor general health predicted HFNS prevalence and frequency, while Chiang Mai location, HFNS frequency, age, diet and beliefs about menopause were associated with problematic HFNS. Location remained significant after controlling for education, occupation and age; location was partially explained by beliefs. Qualitative interview responses illustrated the differences in beliefs about menopause between locations. CONCLUSION: HFNS reports are prevalent with moderate frequency and problem-ratings in these urban centers in Thailand. The results will be included in the broader International Menopause Society study of Climate, Altitude and Temperature (IMS-CAT) of the impact of climate on HFNS.

Raising patient voices in medical education: an assessment of patient perceived effect of social determinants of health conversations and the patient-physician relationship on quality of obstetric care, to inform the development of patient driven medical education curricula.

Background: Conventional medical education lacks the lived experiences of patients which may authentically convey the social determinants of health (SDOH) and resulting health disparities. Videos of first-person patient narratives may prove a valuable education tool in this regard. The objective of this study is to investigate how patient demographics, satisfaction with care, and patient-physician relationships influence obstetric patient interest and willingness to contribute to a SDOH video curriculum by sharing their lived experiences through first-person narratives. Methods: Study design included an anonymous, cross-sectional survey and an optional semi-structured telephone interview. Participants were 18 years old with a live-birth delivery <8 weeks prior to recruitment and received care during their pregnancy at Los Angeles General Medical Center (LAGMC). Variables surveyed included demographics, satisfaction with care, aspects of the patient-physician relationship, perceived utility, and personal interest in contributing to an educational SDOH video. A bivariate analysis was conducted to compare participants' characteristics and responses on interest in contributing and perceived helpfulness of first-person patient SDOH videos. Results: 72.43% of participants (N = 70) believed a patient's first-person video on SDOH would be "Helpful" in preparing physicians to provide competent medical care; however, 71.43% responded "No" to "Interest" in sharing with physicians their experiences with SDOH. English preference and being U.S. born were factors significantly associated with viewing first-person SDOH video as "Helpful" (P > 0.001). Major themes from telephone interviews reflected enthusiasm for first-person patient narratives and perceived benefits of using patient experiences to educate physicians on SDOH. However, participants cited barriers to disclosing SDOH including brief and strictly clinical interactions with physicians, lack of continuity of care, and fear of being judged by physicians. Conclusion: While most participants recognized the utility of addressing social needs in medical education and reported satisfaction with their obstetricians and care, these factors did not uniformly translate into willingness to contribute first-person patient narratives. To improve the representation of patients from racial, ethnic, gender, linguistic, and sexual minorities into medical curricula, further research and strategies are needed to overcome the barriers discouraging patient disclosure of social needs to physicians.