frederick naftolin

ObjectivesTo examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group.MethodsRecently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 μg/day transdermal 17β (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17β-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the …

A medical device is disclosed for monitoring and modulating uterine contractions. The medical device may include a uterine pacemaker and an intravaginal electrode carrier, which may both be located within the body. The intravaginal electrode carrier includes sensing and modulating electrodes that measure uterine electroactivity and apply electrical modulation, respectively. The uterine pacemaker receives the measured uterine electroactivity from the intravaginal electrode carrier and generates the electrical modulation applied by the modulating electrodes. The electrical modulation may be used to inhibit or induce uterine contractions. The intravaginal electrode carrier may be used in addition or as an alternative to an external uterine muscle activity monitor (eg, a tocodynamometer) for a more accurate measure of uterine contractions that is noninvasive.

Evidence suggests that early postmenopausal hormone treatment (MHT) may attenuate metabolic effects on dementia pathogenesis. Using Kronos Early Estrogen Prevention Study (KEEPS) and KEEPS-Continuation data, we investigated heterogeneity in the associations between longitudinal central adiposity (CA), MHT, and cognition, hypothesizing that CA would be related to cognition and that MHT would favorably alter this relationship. KEEPS participants (previously randomized to 48 months treatment with placebo or HT with oral conjugated equine estrogens + progesterone or transdermal 17-β-estradiol+ progesterone) were recruited for KEEPS-Continuation ~10 years post-randomization. Cognitive tests from both studies were analyzed as four-factor scores. Using the original KEEPS data (n=662), growth mixture modeling identified distinct CA trajectories (classes) across 48 months of MHT, which …

In an aspect of the present disclosure, a system and method for controlling uterine contractions is disclosed including receiving data from at least one sensor by a wireless apparatus inserted into the patient's vagina adjacent the cervix. The data includes an indication that a contraction of the uterus is imminent. The method further includes in response to receiving the data, causing a generator circuit of the wireless apparatus to supply electrical energy to an energy applicator of the wireless apparatus that is configured to apply the supplied electrical energy to the uterus of the patient via the cervix of the patient to control contractions of the patient's uterus.

Background Women have higher rates of hypertension at the time of menopausal transition than men. Although elevated systolic and diastolic blood pressures (SBP and DBP) are risk factors for white matter (WM) injury both in women and men, WM hyperintensities (WMH), a marker of WM injury, are more common in women than in men after the age of 60. Thus, women may be vulnerable to the effects of elevated BP on WM integrity during menopausal transition. We investigated the association of BP in recently postmenopausal women with good cardiovascular health with WMH volume assessed 13 years later. Method Women (n = 212; median age = 67; range 58‐72), who were previously enrolled in a multi‐site randomized menopausal hormone therapy trial, Kronos Early Estrogen Prevention Study (KEEPS), participated in the present observational KEEPS Continuation Study. SBP and DBP were measured at …

The narrative for this overview focuses on updating the factors that influence skin aging and the important role estrogens and selective estrogen receptor modulators (SERMs) play in this process (mainly utilizing journal reports and reviews from the last four years). Estrogens have been known and studied for over a century. For many years, it has been recognized that estrogens are important in the maintenance of human skin. Women seek cosmetic and medical treatments to improve dermal health and physical characteristics to enhance their self-perception and inhibit skin aging, particularly in highly visible body areas. The goal: to retain estrogen’s positive benefits while aging and especially at/after menopause where estrogen-deficient skin contributes to the dramatic decline in skin health. In this overview, both background information and recent novel findings are included that cover aging (general mechanisms …

ObjectiveTo test whether volume-based follicular output rate (FORT-V) is superior to diameter based follicular output rate (FORT-D) in predicting the number of mature oocytes. The follicular output rate (FORT) is the ratio between preovulatory follicle count (PFC) and antral follicle count (AFC) and has been proposed as a better predictor of the ovarian response compared with AFC alone.DesignA prospective observational study of 215 consecutive women (80 oocyte donors and 135 in vitro fertilization [IVF] patients) undergoing ovarian stimulation for IVF.SettingUniversity affiliated private IVF center.Patient(s)Women undergoing ovarian stimulation between May 2018 and September 2021.Intervention(s)Manual two-dimensional ultrasound and computer-generated (three-dimensional ultrasound, [3D]) AFCs were performed at baseline. During ovulation induction, follicular growth was monitored in each patient using …

Emerging scientific advances in microbial research linking estrogens and the gut-skin microbiome in reference to dermal health are featured in this narrative review of journal reports and reviews from January 2018 through February 2022. Background information on advances in microbial research along with defining the microbiota and microbiome is presented in brief. The development of and factors that influence the gut microbiome in health and disease as well as the intrinsic and extrinsic factors influencing the skin microbiome and skin aging are summarized. New information on the development and changes of organ microbiomes have exposed similarities between skin and gut structure/function, microbial components/diversity/taxonomy and how they impact the immune response for combating disease and enhancing wellness. Estrogens promote health and support homeostasis in general and directly impact …

Background Research on menopausal hormone therapy (MHT) for the reduction/prevention of cognitive decline or Alzheimer’s disease has been inconsistent. The Women’s Health Initiative Memory Study (WHIMS) revealed elevated incident cognitive impairment for women starting MHT after age >65 with oral conjugated equine estrogens (o‐CEE) treatment, especially among women with diabetes. Subsequently, the Cognitive and Affective substudy of the Kronos Early Estrogen Prevention Study (KEEPS‐Cog) found that MHT initiated soon after menopause caused neither cognitive benefit nor harm. Waist‐to‐hip ratio (WHR) is a measure of central adiposity and a surrogate marker for insulin resistance/prediabetes. To explore effects of MHT in insulin‐resistant states, in younger women, we analyzed WHR as a predictor of cognitive response to MHT in KEEPS‐Cog. Methods KEEPS‐Cog randomized women …

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 …

Estrogen is a pivotal signaling molecule; its production is regulated by the expression of the aromatase (CYP19A1) gene from ovarian and peripheral tissue sites, and it is transmitted via estrogen receptors to influence many important biological functions. However, the narrative for this overview focuses on the decline of 17β-estradiol levels from ovarian sites after menopause. This estrogen-deficient condition is associated with a dramatic reduction in skin health and wellness by negatively impacting dermal cellular and homeostatic mechanisms, as well as other important biological functions. The changes include loss of collagen, elastin, fibroblast function, vascularity, and increased matrix metalloproteinase(s) enzymatic activities, resulting in cellular and extracellular degradation that leads to dryness, wrinkles, atrophy, impaired wound healing/barrier function, decreased antioxidant capacity [i.e., defense …

Background Elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) are risk factors for white matter (WM) injury associated with cognitive decline and dementia. White matter hyperintensities (WMH) on MRI, markers of WM injury, increase with aging and are more common in women than in men after the age of 60. We examined SBP and DBP in relation to WMH volume and diffusion MRI measures of WM integrity in postmenopausal women. Method Women (n=144) with median age of 67 (range 58‐72) and of good cardiovascular health who were previously enrolled in the multi‐site randomized clinical trial, Kronos Early Estrogen Prevention Study (KEEPS), participated in the present observational KEEPS Continuation Study. SBP, DBP, and MRI data were collected approximately 9 years after the end of KEEPS menopausal hormones versus placebo 4‐year interventions. WM integrity was …

In this chapter, the author briefly reviews current theories of the mechanism of steroid hormone action. The distribution of estrogen (E) and progesterone (P) receptors in the pregnant uterus, cervix, and placenta is described, followed by a discussion of the changes in E and P receptor concentrations during pregnancy and the initiation of labor. Evidence for the presence of glucocorticoid receptor systems in the uterus and feto-placental unit is described in the context of the possible role of glucocorticoids in the onset of parturition. The hormone-receptor complexes undergo a process termed “activation” that results in an enhanced affinity for chromatin. The binding of the activated receptor to the chromatin leads, through a process that is as yet poorly understood, to the initiation of new nucleic acid and protein synthesis. The methods for measurement and analysis of steroid receptors depend on the reversible binding of …

Preterm birth (PTB) is one of the leading causes of neonatal morbidities and mortalities. Limited methods are available to physicians for mitigating PTB, thus posing an urgent need to develop effective methods for its prevention. In prior research, a benchtop electronic uterine control device (EUCD) was developed for tocolysis through injection of current pulses. However, the benchtop version is wall tethered and constrains patients to hospitals, i.e., it is unsuitable for deployment in outpatient or home settings. This paper focuses on the development of a mechatronics-based, low-cost, battery-powered, portable, and reproducible EUCD, which is suitable for use in home and clinical environments. The developed mechatronic version is validated for electrical performance with resistive load-tests, which indicate that the mechatronic device can generate current pulses similar to the existing benchtop EUCD …

Objective:Heart fat deposition has been linked to atherosclerosis, and both accelerate after menopause. Hormone therapy (HT) may differentially slow heart fat deposition and progression of atherosclerosis, depending on the specific HT agent or its route of administration. Our objective was to evaluate the effects of different HT agents, oral and transdermal, on associations between heart fat accumulation and atherosclerosis progression, measured by carotid intima-media thickness (CIMT), in recently menopausal women from the Kronos Early Estrogen Prevention Study (KEEPS) trial.Methods:KEEPS was a randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens (o-CEE) or 50 mcg/d transdermal 17β-estradiol (tE 2), compared with placebo, on 48 months progression of CIMT. Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT) volumes were quantified by …

Purpose: Hypertrophic and keloid scar formation occur as a result of aberrant wound healing. Ezrin, a member of the ezrin, radixin, and moesin (ERM) family of proteins, acts as a regulator of cell-to-cell interactions and extracellular matrix (ECM) density and stiffness in tissue remodeling during wound healing. In this study, we examined the expression and activation of ezrin in normal skin and hypertrophic and keloid scars. Methods: Our study consisted of two parts. First, we evaluated the expression and activation of immunoreactive ezrin during the wound healing process in mouse skin. Immunohistochemistry and H-testing were employed. After proving the presence and activation of ezrin in healing skin we compared ezrin expression and activation in normal skin, hypertrophic scar and keloid scars from women undergoing unrelated surgery. Localization and relative amounts of ezrin and phosphorylated ezrin (activated, p-ezrin) protein were examined by immunohistochemistry, H-testing and western blotting. Results: Expression and activation of ezrin was confirmed and shown to increase during wound healing in mouse skin. In women, expression of ezrin and p-ezrin were increased in both hypertrophic and keloid scars relative to normal skin. While both ezrin and p-ezrin were expressed primarily in the epidermal layer, keloids had both increased numbers of lymphocytes and overexpression of activated ezrin in their overgrown dermis. Conclusions: The is the first report of ezrin in scar tissues. Ezrin is an important structural protein in normal and abnormal wound healing. Activated ezrin plays a major role in the formation and integrity of …

The central nervous system of vertebrates, including mammals and humans, plays a pivotal role in the success ofreproduction by assuring complex forms of social and mating behaviors and an integrated neuroendocrine regulation. Evolutionary mechanisms have assured an appropriate intercommunication between brain and neuroendocrine organs, including the gonads. Sex steroids, one of the major players in the communication between the gonads and brain, are involved in the regulation ofcentral nervous system development and adult neural function.The mechanism of action of hormonal steroids in the nervous system, as in other tissues, involves the activation of specific intranuclear receptors that act as transcription factors for specific genes1• 2• In addition, steroid hormones may modulate neuronal excitability by having rapid non-genomic actions~. Neural activity is also modulated by sex-steroid …

The menstrual cycle refers to an orderly progression of events that produces a mature ovum ready for fertilization and an endometrium primed for implantation. Colloquially, the common use of the term menstrual cycle also refers to the periodic shedding of the endometrium that occurs when fertilization and implantation do not occur after ovulation is often termed “menses” by the medical profession and “a period” by the lay public. The tightly orchestrated sequence of events that comprises the menstrual cycle requires appropriate input or drive from the hypothalamic gonadotropin-releasing hormone (GnRH) neuronal network. The decapeptide GnRH is released into the portal circulation in a pulsatile manner, and the pulses must be of sufficient frequency and magnitude to drive pituitary release of the gonadotropins, LH, and FSH. Understanding what is a “normal” menstrual cycle is critical to promoting …

This chapter gives an overview of the relationship between the myometrial contractility and cervical maturation. Cervical maturation, which converts the cervix from a unyielding to a distensible structure, is a key factor in the initiation of normal labor. Dehydroepiandrosterone sulfate is converted to estradiol by the placenta, thus, this treatment raises the levels of local estrogen which is known to promote cervical maturation and myometrial contractility. The relationship between myometrial contractility and cervical maturation in pregnancy and labor is further demonstrated if one considers patients with prolonged pregnancies. In most instances these women have unfavorable, unripe cervices. The authors found that among the cervical parameters dilatation and effacement have been the best predictors of the commencement of labor. Whether the assessment and grading of the cervix could be important in the prevention …