Philip M Sarrel

Yale University | YU · Department of Obstetrics, Gynecology and Reproductive Sciences

The relationship between menopausal hormone therapy (HT) and breast cancer is complex and further complicated by misinformation, perception, and overgeneralization of data. These issues are addressed in this mini-review through the lens of the Women’s Health Initiative (WHI) that has colored the view of HT and breast cancer. In the WHI, unopposed c...

The US Preventive Services Task Force (USPSTF) Draft Recommendation statement on Menopausal Hormone Therapy: Primary Prevention for Chronic Diseases, released in May 2017, perpetuates a major disconnect between the primary population affected, women within roughly 10 years of menopause, and the data cited. Furthermore, major elements of the evidenc...

Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psy...

Objective: While many women undergo menopausal transition while they are in paid employment, the effect of poor working conditions on women's experience of the menopause has received scant empirical attention. We examined associations between employment conditions, work-related stressors, and menopausal symptom reporting among perimenopausal and p...

Bilateral oophorectomy performed in women before they are menopausal induces surgical primary ovarian insufficiency, an acute and chronic deficiency of the hormones normally produced by the ovaries. Without hormone replacement therapy (HRT) most of these women develop severe symptoms of estrogen (E) deficiency and are at increased risk for osteopor...

Large numbers of women transition through menopause whilst in paid employment. Symptoms associated with menopause may cause difficulties for working women, especially if untreated, yet employers are practically silent on this potentially costly issue. This review summarises existing research on the underexplored topic of menopause in the workplace,...

Existing menopause research is dominated by medical and psychosocial paradigms, with key foci on symptom reporting, and the complex interplay of psychological, social and cultural factors that mediate the effects of climacteric symptoms on women’s health and well-being. Work is an underexplored concept and context for menopausal experience in these...

Most women with moderate to severe vasomotor symptoms (VMS) are untreated. This retrospective matched-cohort study aims to evaluate the healthcare resource utilization, work loss, and cost burden associated with untreated VMS. Health insurance claims (1999-2011) were used to match (1:1) women with untreated VMS with control women using propensity s...

We appreciate the careful attention to our article by Prentice et al., and the thoughtful details incorporated into their rejoinder. We must begin our response, however, by highlighting an apparent misunderstanding. Our article is not critical of the Women's Health initiative (WHI),(1) neither explicitly, nor implicitly. The WHI was, of course, an...

Allina and Ryan clearly intended a provocation, and we regret we cannot be entirely cordial in our response. The statistical rebuttal to their arguments is made in our reply to Prentice et al.,(1) and need not be reiterated here. (Am J Public Health. Published online ahead of print October 17, 2013: e1. doi:10.2105/AJPH.2013.301615).

Objectives: We examined the effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59 years. Methods: We derived a formula to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the Women's Health Initiative randomized controlled trial to the entire population of comp...

Menopause occurs in American women at an average age of 51. At this time in their lives a majority of today’s women work outside the home for pay at least part-time, if not full-time (McKinlay, 1988). There is considerable evidence that women who are working experience fewer symptoms at menopause and are better able to cope with the stresses of fam...

To compare the effects of raloxifene and soy phytoestrogens on endothelial function in healthy, postmenopausal women. Randomized, double-blind, placebo-controlled, cross-over trial. Subjects (n = 22; mean age 58.5 years) underwent endothelial function testing at baseline and following 6 weeks of daily raloxifene 60 mg, soy phytoestrogens 55 mg, and...

The effect of gender and female menstrual cycle on human striatal dopamine transporters (DATs) was investigated with single-photon emission computed tomography (SPECT) using the ligand 2beta-carbomethoxy-3beta-(4-[(123)I]iodophenyl)tropane. Ten female subjects aged 18-40 years (25.3+/-7.3 years) were scanned twice during the early follicular and th...

Sexual dysfunction is common in postmenopausal women, but because this problem may be caused by several factors, the primary need for these patients is an initial assessment and accurate diagnosis by the primary care provider. Listening to the patient and clarifying her concerns are important for defining the nature of the problem, its severity and...

Coronary hyperreactivity (CH), characterized by persistent severe vasoconstrictions in response to vasoconstrictor challenge, is oppositely influenced by progesterone (P) and medroxyprogesterone acetate (MPA) treatment in surgically menopausal primates. In this study we tested whether multiweek MPA or dihydrotestosterone (DHT) exposure induced CH i...

Physical performance for walking, reaching, turning, and other common tasks is a major determinant of functional independence after stroke. Current strategies to preserve physical performance focus on prevention of recurrent stroke. Loss of physical performance, however, may occur in the absence of recurrence. To examine this possibility, we measur...

This study was undertaken to assess whether estrogen therapy (ET) reduces the risk of cognitive decline in women with cerebrovascular disease. We conducted a randomized, double-blind trial of estradiol 17beta versus placebo for secondary stroke prevention in 664 postmenopausal women with a recent stroke or transient ischemic attack. The Mini-Mental...

Estrogen deficiency plays a key role in causing the development of cardiovascular disease (CVD) in women. Ovarian hormones have protective effects on cardiovascular risk factors and functions. This chapter summarizes the clinical studies and the studies of ovarian actions affecting cardiovascular functions to determine the significance of these act...

To determine effects of oat and antioxidant vitamin (C 500 mg, E 400 IU) ingestion on endothelial function in overweight, dyslipidemic adults. Randomized, blinded, placebo-controlled, crossover trial Intervention(s): Subjects (16 males > or = age 35; 14 postmenopausal females) were assigned, in random order, to oats (60 g oatmeal), vitamin E (400 I...

The objective of this study was to demonstrate the applicability of laser doppler flowmetry to pre- and posthysterectomy vaginal blood flow assessment. We used laser Doppler flowmetry to measure pre-and postoperational vaginal blood flow in 8 premenopausal women undergoing benign hysterectomies; we also measured serum E2, FSH, FT and administered a...

We assessed whether sociodemographic and clinical characteristics were determinants of clinical trial participation in the Women's Estrogen for Stroke Trial (WEST) by examining data collected on women with a WEST consent visit completed after June 1996. We found no differences in consent rates by education or ethnic group (32% of white women compar...

The purpose of this study was to determine the effects of raloxifene on endothelial function in healthy, postmenopausal women. This was a randomized, double-blind, placebo-controlled crossover trial. Subjects (n = 19; mean age, 61 years) underwent endothelial function testing at baseline and after treatment with placebo or raloxifene (60 mg per day...

Self-reported functional status is a commonly used health measure in clinical settings, yet the optimal approach for assessing function is often debated. To examine the agreement between a self-reported and a performance-based measure of function and the relative ability of each measure to predict long-term health outcomes. Prospective cohort study...

To describe the changes in ovarian hormones caused by natural menopause and hormone replacement therapy that have effects on androgen bioavailability and to describe indications for androgen replacement in postmenopausal women. Review of English language-published research over the last 35 years from January 1, 1966 to June 30, 2001 using MEDLINE....

To evaluate the evidence for and against androgen insufficiency as a cause of sexual and other health-related problems in women and to make recommendations regarding definition, diagnosis, and assessment of androgen deficiency states in women. Evaluation of peer-review literature and consensus conference of international experts. Multinational conf...

Objective: To describe the changes in ovarian hormones caused by natural menopause and hormone replacement therapy that have effects on androgen bioavailability and to describe indications for androgen replacement in postmenopausal women. Design: Review of English language-published research over the last 35 years from January 1, 1966 to June 30, 2...

Based on observational studies indicating a lower risk of stroke and death in women given estrogen replacement therapy (ERT), the Women's Estrogen for Stroke Trial was designed in 1993 as a randomized, double-blind, placebo-controlled investigation. Treatment with 1 mg of estradiol-17β daily was evaluated in 664 postmenopausal women whose mean age...

This study was undertaken to determine the effects of month-long whole grain oat and wheat cereal supplementation on endothelial function following a fatty meal as measured by brachial artery reactivity studies. Fifty healthy adult subjects underwent brachial artery reactivity studies before and after a high-fat meal along with alpha-tocopherol (vi...

Observational studies have suggested that estrogen-replacement therapy may reduce a woman's risk of stroke and death. We conducted a randomized, double-blind, placebo-controlled trial of estrogen therapy (1 mg of estradiol-17beta per day) in 664 postmenopausal women (mean age, 71 years) who had recently had an ischemic stroke or transient ischemic...

To assess the effects of oats and vitamin E on endothelial function following a high-fat meal in healthy adults as measured by brachial artery reactivity studies (BARS). A total of 25 men and 25 women (N=50) were recruited from a community population to participate in this randomized, crossover study. All subjects were free of known vascular diseas...

We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both. Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopaus...

71 Introduction: Observational research has produced conflicting findings concerning the effect of estrogen replacement therapy (ERT) on reducing risk for vascular events or death in women. To test the effect of ERT in women with established cerebrovascular disease, we designed a randomized trial of estradiol-17β(1 mg/day) vs. placebo. Methods: Par...

Investigators continue to define the exact relationship between sexual function and changes in hormonal status during menopause. The availability of different preparations that could replace estrogens and androgens has led to many studies of the use of hormone replacement therapy (HRT) for sexual dysfunction. Dyspareunia due to vaginal dryness appe...

Investigators continue to define the exact relationship between sexual function and changes in hormonal status during menopause. The availability of different preparations that could replace estrogens and androgens has led to many studies of the use of hormone replacement therapy (HRT) for sexual dysfunction. Dyspareunia due to vaginal dryness appe...

After a transient ischemic attack or stroke, the risk for recurrence may be reduced by treatment of hypertension. The purpose of this study was to determine how commonly blood pressure exceeds national guidelines among patients who have had one of these events. Subjects were 644 women participating in a randomized trial of estrogen for secondary st...

In 1991 we developed the Stroke Prognosis Instrument (SPI-I) to stratify patients with transient ischemic attack or ischemic stroke by prognosis for stroke or death in 2 years. In this article we validate and improve SPI-I (creating SPI-II). To validate SPI-I, we applied it to 4 test cohorts and calculated pooled outcome rates. To create SPI-II, we...

Study of the circulatory effects of ovarian hormones has become a subject of increasing interest with the promise of new treatment approaches for the prevention of cardiovascular disease. Work with estrogens is the most extensive and does indicate the benefits outweigh the risks albeit we continue to await the findings of several large, prospective...

Over the past 30 years, numerous studies in invertebrates and vertebrates have established a role of calcium in oocyte maturation as well as in the resumption and progression of follicular development. Polycystic ovarian syndrome (PCO) is characterized by hyperandrogenic chronic anovulation, theca cell hyperplasia, and arrested follicular developme...

The purpose of this paper is to present reported findings of the effects of ovarian steroids on vascular tone. The medical literature was reviewed for relevant contributions. Oestrogen replacement therapy in postmenopausal women is associated with a reduction in mortality from coronary artery disease. Many different cellular actions have been descr...

Ovarian hormones-estrogens, androgens, and progesterone-produce a myriad of effects in the nervous system. The effects of androgens in the brain are mediated through androgen-specific receptors and by the aromatization of testosterone to estradiol. Alterations in the circulating levels of androgens play an important role in psychologic and sexual c...

Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontin...

To report a case of fatal pulmonary embolism associated with the use of i.v. estrogen therapy for menometrorrhagia. Case report. University hospital. A 52-year-old woman with fibroid uterus treated with GnRH analogues with add-back therapy who presented with excessive vaginal bleeding. Intravenous conjugated estrogens were administered for a total...

To investigate the efficacy of esterified estrogens alone and combined with oral androgen on sexual function and menopausal symptoms in postmenopausal women. Twenty postmenopausal women dissatisfied with their estrogen or estrogen-progestin therapy volunteered to enter a double-blind, randomized trial in which they received either oral esterified e...

To describe the use of laser Doppler velocimetry for measurement of vaginal blood flow and report the effects of estrogen compared with estrogen-androgen treatment in post-menopausal women. Literature review of pelvic blood flow studies and sexual function. Findings from a prospective, randomized, parallel study. Normal human volunteers in an acade...

Objective: Estrogen replacement therapy (ERT, defined as estrogen alone) or hormone replacement therapy (HRT, defined as estrogen plus some form of progestogen) may be beneficial for many women as they approach menopause and beyond. If hormones are indicated for some women, optimal continuance is a clinical goal. The North American Menopause Societ...

Observational studies have found that women who take estrogen after menopause are less likely to have a stroke than women who do not take estrogen. Although these findings indicate that estrogen may prevent stroke, an alternative explanation for the improved outcome of estrogen users is that they are healthier before starting therapy than nonusers....

A review of the literature of androgen actions affecting the circulatory system indicates early enthusiasm for use of testosterone in cardiac patients, subsequent disenchantment with androgens due to negative effects on lipid metabolism, and recent renewed interest as new technologies and understandings of the cardio-protective effects of estrogens...

To compare the effects of estrogen with estrogen-androgen treatment on vaginal blood flow velocity and fingertip postocclusive hyperemic blood flow response. Prospective, randomized, parallel, double-blind study. Healthy human volunteers in an academic research environment. Postmenopausal women receiving estrogen replacement therapy for at least 12...

Estradiol retards the development of atherosclerosis. Animal models have suggested that NO may be a critical effector molecule in this cardiovascular protection. In this study, female human umbilical vein endothelial cells (HUVECs) were propagated in phenol red-free gonadal hormone-free medium and pretreated with 17 beta-estradiol (E2). Reduced NO2...

Increased sympathetic drive in symptomatic menopausal women was reduced after estrogen replacement therapy for 4 months, which has a potentially beneficial effect on cardiovascular functions.

We sought to investigate the hypothesis that estrogen replacement therapy ameliorates symptoms in postmenopausal women with syndrome X. Syndrome X (angina pectoris, positive findings on exercise electrocardiography and normal results on coronary angiography) frequently occurs in menopausal women. This observation, in conjunction with the known vaso...

The failure of follicular development that characterizes the menopause leads to a marked reduction in serum levels of estradiol and progesterone. As a result, the majority of women develop symptoms, including hot flushes, sleep disturbance, and vaginal dryness. Long-term consequences of ovarian insufficiency include genital atrophy, osteoporosis, a...

Arterial dysfunction and disease affect a majority of women during their life time. Ovarian hormones inhibit the development of atherosclerosis and play an integral role in the maintenance of normal arterial function. Estrogens act in the liver to improve and maintain lipid profiles and also act in the walls of arteries and in cardiac myocytes to m...

Paroxysmal supraventricular tachycardia (SVT) in premenopausal women is often judged to be related to anxiety, and may be associated with the menstrual cycle. The aim of this study was to determine whether a cyclical variation of episodes of SVT exists and to correlate such variation with cyclical variation in plasma ovarian hormones. 26 women (mea...

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Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17 beta-estradiol improves exercise-i...

This study was undertaken to ascertain whether gynaecological history or a reduction in ovarian hormones are triggers of angina in menopausal women with a positive exercise test and normal coronary arteries. The majority of patients with angina pectoris, a positive exercise test and normal coronary arteries are female, suggesting that the female ge...

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The occurrence of anginal type chest pain in women is greater than that in men. This observation was first made by Sir William Osier at the turn of the century1, and confirmed more recently by a study of over 12,000 men and women in the United States2. However, the prognosis for women and men is different, especially prior to the menopause, with ma...

Actions of estrogens in the walls of arteries have atherosclerotic-inhibiting and hemodynamic effects. Because others participating in this Symposium will be directly addressing the role of estrogens in preventing atherosclerotic cardiovascular disease, this presentation will focus on the hemodynamic effects of ovarian hormones.

Estrogen and progestogen effects on arterial function in postmenopausal women are a focus of current investigative research and a natural out-growth of numerous animal studies carried out during the last thirty to forty years. Arterial systems which have been studied include the aorta and coronary vessels, carotid and cerebral arteries, the uterine...

Few topics in women's medicine today are as fraught with confusion and controversy as the question of appropriate treatment for menopausal symptoms and the prevention of negative long term health outcomes common to post-menopausal women. Cardiovascular disease (CVD), osteoporosis, and cancer -- the most common causes of death, disability and impair...

Oestradiol-17 beta causes relaxation of isolated coronary arteries and increases blood flow in several vascular beds in human beings and animals. Oestrogen replacement therapy is associated with a lower incidence of cardiovascular disease, but the acute effects of oestradiol-17 beta on myocardial ischaemia are unknown. We have studied the acute eff...

During their premenopausal years, women have a lower risk than men of getting cardiovascular disease. This protection continues after the menopause if women receive oestrogen replacement. Based on new experimental evidence we propose that some of the cardiovascular benefits of oestrogen replacement therapy may be due to a long-term calcium antagoni...

Our aim was to evaluate the hypotheses that women with severe angina and normal coronary arteries (syndrome X) have an increased incidence of hysterectomy and show a positive cardiac response to 17 beta-estradiol replacement therapy. The gynecologic histories of 30 women with syndrome X were determined. Anginal and 17 beta-estradiol insufficiency s...

1. The effect of 17β-oestradiol on cardiac cell contraction, inward Ca2+ current and intracellular free Ca2+ ([free Ca2+](i)) was investigated in guinea-pig single, isolated ventricular myocytes. The changes of cell length were meausred by use of a photodiode array, the voltage-clamp experiments were performed with a switch clamp system and [free C...

We assessed the acute effect of 17 beta-estradiol on coronary artery constrictor responses to endothelin-1. 17 beta-Estradiol significantly shifted endothelin-1, calcium, or BAY K 8644 concentration-dependent contraction curves to the right in endothelium-denuded coronary arteries isolated from nonpregnant female rabbits. The -log 50% effective dos...