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Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.
Singhal, V, Bose, A, Slattery, M, Haines, MS, Goldstein, MA, Gupta, N, Brigham, KS, Ebrahimi, S, Javaras, KN, Bouxsein, ML, et al
The Journal of clinical endocrinology and metabolism. 2021;(7):2021-2035
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CONTEXT Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
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Lessons from KEEPS: the Kronos Early Estrogen Prevention Study.
Miller, VM, Taylor, HS, Naftolin, F, Manson, JE, Gleason, CE, Brinton, EA, Kling, JM, Cedars, MI, Dowling, NM, Kantarci, K, et al
Climacteric : the journal of the International Menopause Society. 2021;(2):139-145
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The Kronos Early Estrogen Prevention Study (KEEPS) was a randomized, double-blind, placebo-controlled trial designed to determine the effects of hormone treatments (menopausal hormone treatments [MHTs]) on the progression of carotid intima-medial thickness (CIMT) in recently menopausal women. Participants less than 3 years from menopause and without a history of overt cardiovascular disease (CVD), defined as no clinical CVD events and coronary artery calcium < 50 Agatston units, received either oral conjugated equine estrogens (0.45 mg/day) or transdermal 17β-estradiol (50 µg/day), both with progesterone (200 mg/day for 12 days/month), or placebo pills and patches for 4 years. Although MHT did not decrease the age-related increase in CIMT, KEEPS provided other important insights about MHT effects. Both MHTs versus placebo reduced the severity of menopausal symptoms and maintained bone density, but differed in efficacy regarding mood/anxiety, sleep, sexual function, and deposition of β-amyloid in the brain. Additionally, genetic variants in enzymes for metabolism and uptake of estrogen affected the efficacy of MHT for some aspects of symptom relief. KEEPS provides important information for use of MHT in clinical practice, including type, dose, and mode of delivery of MHT recently after menopause, and how genetic variants in hormone metabolism may affect MHT efficacy on specific outcomes.
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[Topical hormonal treatment in anti-aging of the skin].
Bayerl, C
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2020;(10):786-790
Abstract
Topical hormonal treatment allows anti-aging of the skin when used during and after the menopause without an increase in the blood level of hormones. Natural hormones are only prescribed by medical doctors. In controlled clinical studies versus placebo and application for months, an increase in skin quality parameters, reduction of dryness, increase of glycosaminoglycanes, increase in elastic fibers und increase of collagen precursers and collagen fibers on the mRNA and protein level could be shown, the latter proven by biopsies. Skin with dramatic sun-damage does not respond to this treatment option. Patients with melasma or seborrhoe should not be treated with hormonal topical preparations. Compared to the natural hormones, phytotherapeutics do not bind to hormone receptors in relevant levels. Growth hormones should not be used in anti-aging treatment due to a potential carcinogenic effect.
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Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress.
Liu, T, Li, N, Yan, YQ, Liu, Y, Xiong, K, Liu, Y, Xia, QM, Zhang, H, Liu, ZD
Phytotherapy research : PTR. 2020;(3):435-447
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Skin undergoes degenerative changes as it ages, which include the loss of elasticity, reductions in the epidermal thickness and collagen content, elastic fiber degeneration, and increased wrinkling and dryness. Skin aging can be significantly delayed by the administration of estrogen. Estrogen deficiency following menopause results in atrophic skin changes and the acceleration of skin aging. Estrogen administration has positive effects on human skin by delaying or preventing skin aging manifestations, but the use of estrogen replacement is a risk factor for breast and uterine cancer. Phytoestrogens are a large family of plant-derived molecules possessing various degrees of estrogen-like activity; they exhibit agonist or antagonist estrogenic properties depending on the tissue. These molecules could be ideal candidates to combat skin aging and other detrimental effects of hypoestrogenism. In this paper, we review the effects of phytoestrogens on human skin and the mechanisms by which phytoestrogens can alleviate the changes due to aging.
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Acupuncture or phy(F)itoestrogens vs. (E)strogen plus progestin on menopausal symptoms. A randomized study.
Palma, F, Fontanesi, F, Facchinetti, F, Cagnacci, A
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(11):995-998
Abstract
The effect of acupuncture and phytoestrogens on climacteric symptoms was compared to the effect of hormone therapy (HT) with estrogen plus progestin. A total of 75 postmenopausal women with hot flushes were randomized to receive for 3 months conjugated estrogens/medroxyprogesterone acetate (0.30 mg/1.5 mg/d), acupuncture weekly or soy isoflavones (75 mg/2/d). Evaluations were performed prior to, at the end, and 3 months after treatments. Main outcomes were modification of the Greene's climacteric scale and menopause quality of life (MenQoL). The Greene's score significantly declined (p < .05) during HT (-5.6 ± 3.1), acupuncture (-6.9 ± 4.5) and phytostrogens (-3.4 ± 4.3) (p < .05 vs. HT). Mean Greene's vasomotor sub-score declined less during phytoestrogens than HT (-0.8 ± 2.0 vs. -2.0 ± 1.9; p < .05) and a ≥ 80% reduction was observed in 17.4% of women on phytoestrogens (p < .05 vs. HT), 44% of women on HT, and 41.7% of women on acupuncture. MenQoL score improved similarly (p < .05) during HT (-1.4 ± 1.3), acupuncture (-1.7 ± 1.0) and phytoestrogens (-1.0 ± 1.3). Three months after treatment end, benefits on MenQoL were conserved more following acupuncture than HT (p < .006). The present data indicate that acupuncture, and in lesser extent phytoestrogens, can be effective therapies for climacteric symptoms. Trial registration: EudraCT Number 2008-006053-4.
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SLCO1B1 genetic variation and hormone therapy in menopausal women.
Moyer, AM, de Andrade, M, Faubion, SS, Kapoor, E, Dudenkov, T, Weinshilboum, RM, Miller, VM
Menopause (New York, N.Y.). 2018;(8):877-882
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OBJECTIVE Response to menopausal hormone therapy (MHT) shows individual variation. SLCO1B1 encodes the OATP1B1 transporter expressed in the liver that transports many endogenous substances, including estrone sulfate, from the blood into hepatocytes. This study evaluated the relationship between genetic variation in SLCO1B1 and response to MHT in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester, MN. METHODS KEEPS participants were randomized to oral conjugated equine estrogen (n = 33, oCEE), transdermal 17β-estradiol (n = 33, tE2), or placebo (n = 34) for 48 months. Menopausal symptoms (hot flashes, night sweats, insomnia, palpitations) were self-reported before treatment and at 48 months. Estrone (E1), E2, and sulfated conjugates (E1S, E2S) were measured using high-performance liquid chromatography-tandem mass spectrometry. SLCO1B1 rs4149056 (c.521T>C, p.Val174Ala) was genotyped using a TaqMan assay. RESULTS After adjusting for treatment, there was a significant association between the SLCO1B1 rs4149056 TT genotype (encoding normal function transporter) and lower E1S, E1S/E1, and E2S (P = 0.032, 0.010, and 0.008, respectively) compared with women who were heterozygous (TC) or homozygous (CC) for the reduced function allele. The interactions between genotype, treatment, and E2S concentration were stronger in women assigned to tE2 (P = 0.013) than the women taking oCEE (P = 0.056). Among women assigned to active treatment, women with the CT genotype showed a significantly greater decrease in night sweats (P = 0.041) than those with the TT genotype. CONCLUSIONS Individual variation in sulfated estrogens is explained, in part, by genetic variation in SLCO1B1. Bioavailability of sulfated estrogens may contribute to relief of night sweats.
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[Shereshevsky-Turner syndrome: Estrogen replacement therapy and cardiovascular risk factors].
Yevstigneeva, OA, Andreeva, EN, Grigoryan, OR, Volevodz, NN, Melnichenko, GA, Dedov, II
Terapevticheskii arkhiv. 2017;(10):48-53
Abstract
AIM: To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. SUBJECTS AND METHODS From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. RESULTS 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. CONCLUSION By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.
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Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS).
Taylor, HS, Tal, A, Pal, L, Li, F, Black, DM, Brinton, EA, Budoff, MJ, Cedars, MI, Du, W, Hodis, HN, et al
JAMA internal medicine. 2017;(10):1471-1479
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IMPORTANCE Sexual dysfunction, an important determinant of women's health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. OBJECTIVE To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS), a 4-year prospective, randomized, double-blinded, placebo-controlled trial of menopausal hormone therapy in healthy, recently menopausal women. Of 727 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. INTERVENTIONS Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 µg/d transdermal 17β-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. MAIN OUTCOMES AND MEASURES Aspects of sexual function and experience (desire, arousal, lubrication, orgasm, satisfaction, and pain) were assessed using the Female Sexual Function Inventory (FSFI; range, 0-36 points; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. RESULTS The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, -0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E2 treatment was associated with a significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95% CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E2 treatment compared with placebo (67%; 95% CI, 55%-77% vs 76%; 95% CI, 67%-83%; P = .04). For o-CEE there was no significant reduction in the odds of LSF. CONCLUSIONS AND RELEVANCE Treatment with t-E2 modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00154180.
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Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.
Pizot, C, Boniol, M, Mullie, P, Koechlin, A, Boniol, M, Boyle, P, Autier, P
European journal of cancer (Oxford, England : 1990). 2016;:138-54
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BACKGROUND Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. METHODS After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). RESULTS The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. CONCLUSION Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out.
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ENDOCRINE DILEMMA: Managing menopausal symptoms after breast cancer.
Eden, J
European journal of endocrinology. 2016;(3):R71-7
Abstract
Managing the symptoms of menopause after a diagnosis of breast cancer offers some unique clinical challenges. For some women, vasomotor symptoms can be severe and debilitating, and hormone therapy is at least relatively contraindicated. Non-oestrogen therapies for hot flushes include SSRIs, clonidine, gabapentin and perhaps black cohosh extracts. Vulvovaginal atrophy can usually be alleviated by simple moisturizers, although some may need specialized physiotherapy such as vaginal dilators. In a small number, topical oestrogens may be the only treatment that works. The CO2 laser may be a novel, non-oestrogen therapy to alleviate this unpleasant symptom. Bone loss can be accelerated in some patients on AIs or those who had early menopause induced by chemotherapy.