To investigate changes in plasma lipid and lipoprotein levels induced by peroral oestrogen replacement and transdermal oestradiol gel therapy.
Design
The effects of peroral oestradiol valerate tablets (2 mg) and placebo gel were compared with 1g transdermal oestradiol gel (1mg oestradiol) and placebo tablets in a randomised, double-blind, double-dummy study for 6 months.
Setting
Department of Internal Medicine, University of Oulu and Oulu Deaconess Institute, Oulu, Finland.
Population
Seventy-nine hysterectomised, postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group.
Main Outcome Measures
Cholesterol and triglycerides in total plasma and in various lipoprotein fractions, and sex hormones.
Results
In the peroral oestrogen group total and LDL cholesterol were decreased and HDL cholesterol and triglycerides were increased. In the oestradiol gel group plasma total, LDL and VLDL cholesterol and the ratio of LDL/HDL cholesterol were significantly decreased, but no change in HDL cholesterol and triglycerides was observed. Overall the decrease in LDL levels was correlated with the increase in oestrogen levels.
Conclusions
Both peroral and transdermal replacement therapy had beneficial effects on plasma lipids by lowering total and LDL cholesterol and LDL/HDL cholesterol ratio. These changes seem to be associated with changes in oestrogen levels.
oral estrogen versus transdermal estradiol gel lipid effects, peroral estradiol valerate LDL cholesterol postmenopausal women, transdermal estradiol gel triglycerides HDL cholesterol, hormone replacement therapy lipid lipoprotein changes menopause, estrogen route of administration metabolic effects randomized trial, postmenopausal estrogen therapy cardiovascular lipid profile, double-blind estrogen replacement LDL HDL cholesterol ratio, hysterectomised women estrogen replacement VLDL cholesterol, transdermal versus oral estrogen metabolic outcomes, estradiol gel placebo controlled lipid lowering postmenopausal
PMID 9389782 9389782 DOI 10.1111/j.1471-0528.1997.tb11566.x 10.1111/j.1471-0528.1997.tb11566.x Karjalainen et al. 1997, Karjalainen 1997
Cite this article
Karjalainen, A., Heikkinen, J., Savolainen, M. J., Bäckström, A. C., Salinto, M., & Kesäniemi, Y. A. (1997). Metabolic changes induced by peroral oestrogen and transdermal oestradiol gel therapy. British journal of obstetrics and gynaecology, 104 Suppl 16(s16), 38-43. https://doi.org/10.1111/j.1471-0528.1997.tb11566.x
Karjalainen A, Heikkinen J, Savolainen MJ, Bäckström AC, Salinto M, Kesäniemi YA. Metabolic changes induced by peroral oestrogen and transdermal oestradiol gel therapy. Br J Obstet Gynaecol. 1997;104 Suppl 16(s16):38-43. doi:10.1111/j.1471-0528.1997.tb11566.x
Karjalainen, Anna, et al. "Metabolic changes induced by peroral oestrogen and transdermal oestradiol gel therapy." British journal of obstetrics and gynaecology, vol. 104 Suppl 16, no. s16, 1997, pp. 38-43.
The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.
Tan-Kim J et al., 2023·American journal of obstetrics and gynecology
Vaginal estrogen is considered to be the standard of care for recurrent urinary tract infection prevention in women with hypoestrogenism. However, literature supporting its use is limited to small clinical trials with narrow generalizability. This study aimed to assess the association between vaginal estrogen prescription and the frequency of urinary tract infections over the following year in a diverse population of women with hypoestrogenism. Secondary objectives included evaluation of medication adherence and predictors of postprescription urinary tract infection. This multicenter retrospective review included women who were prescribed vaginal estrogen for the indication of recurrent urinary tract infection from January 2009 through December 2019. Recurrent urinary tract infection was defined as having ≥3 positive urine cultures (separated by at least 14 days) in the 12 months preceding the index vaginal estrogen prescription. Patients were asked to fill their prescriptions and continue care within Kaiser Permanente Southern California system for at least 1 year. Exclusion criteria included anatomic abnormalities, malignancy, or mesh erosion of the genitourinary tract. Data on demographics, medical comorbidities, and surgical history were collected. Adherence was captured through refill data after the index prescription. Low adherence was defined as no refills; moderate adherence was defined as 1 refill; high adherence was defined as ≥2 refills. Data were abstracted from the electronic medical record system using the pharmacy database and diagnosis codes. A paired t test was used to compare pre- and postprescription urinary tract infections over the year preceding and following the vaginal estrogen prescription. A multivariate negative binomial regression was used to evaluate predictors of postprescription urinary tract infection. The cohort included 5638 women with a mean (±standard deviation) age of 70.4 (±11.9) years, body mass index of 28.5 (±6.3) kg/m2, and baseline urinary tract infection frequency of 3.9 (±1.3). Most of the participants were White (59.9%) or Hispanic (29.7%) and postmenopausal (93.4%). The mean urinary tract infection frequency in the year following the index prescription decreased to 1.8 (P<.001) from 3.9 in the year preceding the prescription, which is a 51.9% reduction. During the 12 months after the index prescription, 55.3% of patients experienced ≤1 urinary tract infections, and 31.4% experienced no urinary tract infections. Significant predictors of postprescription urinary tract infection included age of 75 to 84 years (incident rate ratio, 1.24; 95% confidence interval, 1.05-1.46) and >85 years (1.41; 1.17-1.68), increased baseline urinary tract infection frequency (1.22; 1.19-1.24), urinary incontinence (1.14; 1.07-1.21), urinary retention (1.21; 1.10-1.33), diabetes mellitus (1.14; 1.07-1.21), and moderate (1.32; 1.23-1.42) or high medication adherence (1.33; 1.24-1.42). Patients with high medication adherence demonstrated more frequent postprescription urinary tract infections than patients with low adherence (2.2 vs 1.6; P<.0001). In this retrospective review of 5600 women with hypoestrogenism who were prescribed vaginal estrogen for the prevention of recurrent urinary tract infections, the frequency of urinary tract infection decreased by more than 50% in the following year. Baseline urinary tract infection frequency, increasing age, urinary incontinence or retention, and diabetes were associated with an increased risk of postprescription urinary tract infection. The paradoxical finding that women with moderate and high medication adherence experienced the lowest-magnitude reduction in urinary tract infection frequency may represent unobserved selection or unmeasured confounding.
We agree with Lega and colleagues[1][1] that menopausal hormone therapy (MHT) has been shown in randomized controlled trials (RCTs) to be effective and safe for treating problematic vasomotor symptoms related to menopause. We also agree that treating menopausal vasomotor symptoms is important to
Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.