Benefits Of Estrogen Therapy Research Articles

FRI451 Effect Of Estrogen Replacement On Various Metabolic Parameters In Turner’s Syndrome

Abstract Disclosure: I. Mishra: None. S. Jena: None. A.K. Baliarsinha: None. Turner’s Syndrome is a rare genetic disorder caused by complete or partial X chromosome monosomy in a phenotypic female, and is associated with increased morbidity and mortality for cardiovascular diseases, impaired glucose tolerance, liver dysfunction and dyslipidemia. Estrogen therapy was initially focused on pubertal induction and preservation of bone health. Recent longitudinal studies have shown the beneficial effect of estrogen therapy on various metabolic parameters, liver dysfunction and insulin resistance in these patients.To study the effect of estrogen therapy on various metabolic parameters, a cohort of 24 adolescent girls with Turner’s Syndrome planned for hormonal replacement therapy were recruited. Baseline data of detailed history, clinical examination, biochemical evaluation including glycemic status, lipid profile, liver function test and fibroscan were collected. At 6 month follow-up of estrogen replacement, repeat biochemical evaluation and fibroscan were done.The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp.). The normal distribution of data was confirmed with Shapiro-Wilk's test and appropriate parametric tests were employed. Mean and standard deviation were computed for all continuous variables. At baseline visit and 6 month follow up, statistically significant improvement, was found in fasting plasma glucose, post-prandial plasma glucose, fasting insulin, HOMA-IR, VLDL and total bilirubin with estrogen therapy. Maximum reduction (p <0.001) was seen in LDL, AST, ALT and fibroscan values .No improvement was seen in triglyceride, HDL, direct bilirubin and ALP levels. Estrogen has been shown to improve insulin sensitivity and suppress gluconeogenesis by transcription factor Foxo1(1). Hepatoprotective role of estrogen has been explained by anti-inflammatory effects and protection from oxidative stress, mainly mediated via β estrogen receptor(2). Beneficial effects of estrogen on lipid profile have been verified in several studies. We conclude that the benefits of estrogen therapy in Turner’s Syndrome are much beyond the limit of puberty induction and bone health and pleiotropic actions of estrogen still need to be elucidated with further studies. Reference: (1) Yan et al; Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1. Diabetes 1 February 2019; 68 (2): 291–304. (2) Koulouri O et al. Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen. ClinEndocrinol (Oxf). 2008 Aug;69(2):306-10. Presentation: Friday, June 16, 2023

Annals for Educators - 4 February 2020.

Annals for Educators - 4 February 2020.

Impact of new systemic oral and local, hormonal and non-hormonal treatments on genitourinary syndrome and Vulvo-Vaginal-Atrophy (VVA) through the menopausal transition: the right therapy in patients at risk

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment, cardiovascular and oncologic risk factor, or other factors. Therefore, local estrogen treatment is still controversial due to the systemic absorption of estradiol and its potential effects on the breast and endometrium.The fact that up to 26% of women using systemic hormonal therapy continue to experience symptoms of urogenital atrophy is sufficient reason to justify not recommending systemic hormonal therapy in women with vaginal symptoms only; many women initially require a combination of systemic and local estrogen therapy, especially when it is used at low doses.Intravaginal application of DHEA as an alternative treatment compared to local estrogen therapy. Intravaginal DHEA does not increase serum E2 levels and may be a better option for long term treatment of VVA as there is no increase in serum E2 levels with DHEA. Previous data have shown that intravaginal dehydroepiandrosterone (DHEA, prasterone) improved all the domains of sexual function, an effect most likely related to the local formation of androgens from DHEA.As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), which seems to be effective in genitourinary symptoms.There is now a new alternative to systemic hormone therapy with estrogen/gestagens. The tissue-selective estrogen complex (TSEC) which combines a SERM (bazedoxifene, BZA) with conjugated equine estrogens (CEE) is designed not only to improve menopausal symptoms but to prevent osteoporosis, while maintaining the benefits of estrogen therapy on vasomotor symptoms and vulvovaginal atrophy, but antagonizing stimulatory effects on the endometrium and mammary gland. The two studied doses of BZA/CEE (20 mg BZA + 0.425 mg CEE and 20 mg BZA + 0.625 mg CEE) have been shown to improve the percentage of superficial cells, reducing the percentage of basal cells. Thus, 20 mg BZA + 0.625 mg CEE reduces the severity of symptoms caused by atrophic vulvovaginitis by 56% and normalizes vaginal histology and pH. This efficacy persists for 2 years.Here we aim to evaluate current experimental and actual clinical strategies to achieve the main therapeutic goal for genitourinary syndrome and VVA in menopause which is the relief of symptoms, a better quality of life and women’ s health in menopausal women not eligible for Hormonal Replacement Therapy (HRT).

Differential Effects of E2 on MAPK Activity in the Brain and Heart of Aged Female Rats

Aging and the coincident loss of circulating estrogens at menopause lead to increased risks for neurological and cardiovascular pathologies. Clinical studies show that estrogen therapy (ET) can be beneficial in mitigating these negative effects, in both the brain and heart, when it is initiated shortly after the perimenopausal transition. However, this same therapy is detrimental when initiated >10 years postmenopause. Importantly, the molecular mechanisms underlying this age-related switch in ET efficacy are unknown. Estrogen receptors (ERs) mediate the neuroprotective and cardioprotective functions of estrogens by modulating gene transcription or, non-genomically, by activating second messenger signaling pathways, such as mitogen activated protein kinases (MAPK). These kinases are critical regulators of cell signaling pathways and have widespread downstream effects. Our hypothesis is that age and estrogen deprivation following menopause alters the expression and activation of the MAPK family members p38 and ERK in the brain and heart. To test this hypothesis, we used a surgically induced model of menopause in 18 month old rats through bilateral ovariectomy (OVX) followed by an acute dose of 17β-estradiol (E2) administered at varying time points post-OVX (1 week, 4 weeks, 8 weeks, or 12 weeks). Age and E2 treatment differentially regulated kinase activity in both the brain and heart, and the effects were also brain region specific. MAPK signaling plays an integral role in aging, and the aberrant regulation of those signaling pathways might be involved in age-related disorders. Clinical studies show benefits of ET during early menopause but detrimental effects later, which might be reflective of changes in kinase expression and activation status.

Short-term Use of Unopposed Estrogen

WHEN RECRUITMENT FOR THE WOMEN’S HEALTH Initiative (WHI) began in 1993, hormone therapy (HT) was prescribed for a variety of reasons that ranged from the management of menopausal symptoms to the prevention of chronic disease, and the WHI focused on documenting the risks and benefits of HT use for chronic disease prevention. In 2004, one of the first publications from the WHI reported the balance of risks and benefits during active intervention with unopposed estrogen among women with previous hysterectomy. Based on data collected through the end of the trial’s intervention phase, women randomly assigned to estrogen had a significantly increased risk of stroke and reduced risk of hip fracture and possibly breast cancer compared with women receiving placebo. There was no overall effect of estrogen on a global index of risks and benefits including coronary heart disease. These findings were revolutionary and changed practice. Today, indications for HT are narrow, and many physicians take pause before performing elective bilateral salpingooophorectomy during hysterectomy. Short-term unopposed estrogen therapy is still a mainstay in managing menopausal symptoms among women with previous hysterectomy, although questions remain regarding the safety of this treatment, including whether there is a safe duration of estrogen use and whether there are long-term risks and benefits of estrogen therapy that persist after cessation. Once again, data from the WHI study in this issue of JAMA help to provide guidance. To assess the long-term effects of unopposed estrogen therapy and the balance of risks and benefits over time, LaCroix and colleagues report follow-up of women who completed the intervention phase of the WHI estrogen-alone study. Seventy-eight percent of eligible women gave consent for continued observational follow-up through a mean of 10.7 years from baseline. During follow-up, the increased risk of stroke observed previously did not persist after cessation of estrogen therapy, whereas the previously observed significant reduction in hip fractures was eliminated. Other risks and benefits associated with estrogen therapy during the intervention phase were not maintained; however, the reduced incidence of breast cancer persisted. This finding is inconsistent with a longstanding, corroborated body of evidence and raises the possibility that other important factors modify documented risks and benefits of estrogen therapy among these long-term WHI participants. Building on previous evidence that highlights the importance of age at HT initiation, LaCroix and colleagues postulate that an age effect may also underlie some of their findings. For example, the authors expected fewer adverse effects among women who initiated estrogen at the time of menopause, and they found that for every 10 000 women aged 50 to 59 years taking estrogen, there were 12 fewer myocardial infarctions, 13 fewer deaths, and 18 fewer adverse events compared with those taking placebo, and they conclude the overall benefits of estrogen therapy may be greater among younger women. In contrast, a recent report by Beral et al from the Million Women Study demonstrates an adverse effect of postmenopausal estrogen use on breast cancer risk, with a significantly increased risk among women beginning therapy within 5 years of menopause and little or no increased risk among those beginning therapy 5 or more years after menopause. These findings derive from an analysis of 15 759 incident breast cancer cases diagnosed during 4 million patient-years of follow-up. Sixty-eight percent of women enrolled in the WHI were older than age 60 years at randomization. Given this fact and the findings from the Million Women Study, an important question that emerges is whether the WHI population is appropriate for reaching definitive conclusions regarding younger women and the risk of breast cancer associated with HT. In addition to a potential age effect on the risk-to-benefit profile of HT, overall duration of HT use remains a major concern. The median adherent time (defined as women taking 80% of study pills) among women in the WHI estrogenalone group was 3.5 years. Thus, the WHI results do not address the balance of risks and benefits associated with longerterm estrogen use. Longer unopposed estrogen use may

Does Short-Term Estrogen Therapy Produce Lasting Benefits in Brain?

The question of whether estrogen therapy should be used in postmenopausal women is a topic filled with controversy and debate. In vitro and animal studies clearly show that estrogens (most often 17 -estradiol) are neuroprotective (1), can enhance hippocampal and cortical function (2), improve cognitive performance (3), and prevent or reduce age-related cognitive decline (4, 5). Estrogen therapy, however, is not without risks. These include increased production of liver proteins such as sex hormone-binding globulin and C-reactive protein as well as increased risk of thromboembolism and stroke and breast and uterine cancers (6–9). Although positive effects on cognitive performance have been observed (10), negative results also have been reported. For example, the recent Women’s Health Initiative Memory Study showed an increased ( 2-fold) risk of dementia among women receiving the combination of oral conjugated equine estrogens and medroxyprogesterone acetate (11) and a trend toward increased risk of dementia among women receiving conjugated equine estrogens alone (12). This was a very large study of over 7000 women with a mean age of 69 yr. Another recent study likewise showed increased risk of cognitive decline among long-term users of estrogen therapy, particularly among women who initiated therapy at older ages (13). These findings have raised serious concerns about the long-term use of estrogen therapy in older postmenopausal women. As a result, women who are prescribed therapy for the treatment of menopausal symptoms are encouraged to limit therapy to the lowest possible dose and duration. But might short-term therapy initiated around the time of menopause confer some lasting benefit to the brain? Quite possibly so, according to a recent report by Rodgers et al. (14). The authors tested whether treating rats with estradiol for 40 d after being ovariectomized at middle age would have lasting benefits on working memory performance months after discontinuing the hormone treatment. Results show that 40 d treatment initiated at the time of ovariectomy was as effective as sustained treatment at enhancing working memory performance when rats were tested 1, 3, 5, and 7 months after discontinuing hormone. This finding demonstrates that, in rats, a relatively brief course of hormone therapy initiated in middle age can have long-lasting benefits on cognitive performance. The implications of this observation are profound. Estrogen therapy is proven to be very effective at mitigating perimenopausal symptoms that, for many women, result in significant improvements in quality of life during the perimenopausal transition (7, 15). Some of the risks of estrogen therapy can be mitigated by using transdermal as opposed to oral therapy (16). Adding a progestin will mitigate the increased risk of uterine cancers but may increase the risk of breast cancer (17). Given the concerns, women and physicians are faced with the difficult task of assessing on an individual basis not only the immediate benefits of hormone therapy but also the risks and benefits of an extended course of treatment. Rodgers’ findings, if true in humans, would provide another important benefit of short-term estrogen therapy during the perimenopause, namely a lasting benefit on cognitive performance. What is the likelihood that a lasting benefit of estrogen therapy on brain function occurs in humans? Several observational studies have reported that past postmenopausal use of estrogen therapy is associated with significant reductions in the risk of developing Alzheimer’s disease (AD) among older postmenopausal women (18). One study evaluated 1866 women living in Cache County, Utah, with a mean age of approximately 74.4 yr (19).

The Pairing of a Selective Estrogen Receptor Modulator, Bazedoxifene, with Conjugated Estrogens as a New Paradigm for the Treatment of Menopausal Symptoms and Osteoporosis Prevention

The menopausal transition is associated with decreased ovarian function and concomitant decline in estrogen production, which may result in physiological effects such as hot flashes, reduced bone mass, and altered lipid profile. It is well established that these unfavorable changes are effectively offset with estrogen therapy (ET) or, in women with a uterus, estrogens in combination with a progestin (hormone therapy). Selective estrogen receptor (ER) modulators (SERMs), which exhibit both ER agonist and antagonist activities depending on the target tissue, have been regarded as offering the potential to provide the benefits of ET and hormone therapy with an improved safety and tolerability profile. To date, no SERM alone has demonstrated an ideal benefit-risk profile for menopausal therapy. The tissue-selective estrogen complex, or the pairing of a SERM with estrogens, may provide an optimal blend of ER agonist and antagonist activities. We evaluated the physiological profile of this novel therapeutic paradigm by using various in vivo models to assess uterine, vasomotor, lipid, and skeletal responses to a tissue-selective estrogen complex partnering bazedoxifene with conjugated estrogens (CE). Bazedoxifene at 3.0 mg/kg effectively antagonized CE-induced uterine stimulation without reversing the positive effects of CE on vasomotor instability. When paired with CE, bazedoxifene at 3.0 mg/kg reduced total cholesterol levels by up to 20% compared with CE alone and significantly increased total bone density relative to control. These preclinical findings showed that the appropriate dose combination of bazedoxifene/CE exhibits positive vasomotor, lipid, and skeletal responses with minimal uterine stimulation.

DNA microarray–based analysis of single nucleotide polymorphisms may be useful for assessing the risks and benefits of hormone therapy

Objective To determine what percentage of women can be given individualized counseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen therapy and hormone therapy such as thrombosis, myocardial infarction, breast cancer, and bone protection. Design Cross-sectional study. Setting Academic research institution. Patient(s) A consecutive series of 2,507 perimenopausal and postmenopausal women. Intervention(s) Peripheral venous puncture and multiplex polymerase chain reaction on a microarray system. Main outcome measure(s) Analysis of 22 SNPs of 17 genes: AGTMet235Thr, APOECys112Arg, APOEArg158Cys, COMTVal158Met, CYP17–34T>C, CYP191558C>T, CYP19Arg264Cys, CYP1A16235T>C, CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1Asn453Ser, HSD17B1–27A>C, ER-αIVS-401T>C, prothrombin20210G>A, factor V Leiden, eNOS–786T>C, eNOSGlu298Asp, MRSer810Leu, MTHFR677C>T, PAI 15G>4G, SRD5A2Val89Leu, and VDRb>B. Result(s) Among the women in the study, 66% had at least two homozygous mutant SNPs of interest. A thrombophilic disposition was found in 9.9% of women, and 23% of women had at least two SNPs associated with an increased risk of breast cancer (COMT, CYP17, CYP19, CYP1A1, and CYP1B1). The SNPs predisposing women to cardiovascular pathologies (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3% of women. Carriage of SNPs predisposing to early postmenopausal bone loss and osteoporosis (ER-α and VDR) were found in 26.7% of women. Conclusion(s) These data suggest that the assessment of SNPs associated with risks and benefits of estrogen/hormone therapy may be a new means to individualize counseling about and prescription of estrogen/hormone therapy in up to 66% of women.

Transdermal oestrogen therapy protects postmenopausal liver transplant women from osteoporosis. A 2-year follow-up study

Background/Aims : Hormone replacement therapy (HRT) prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the benefits of oestrogen therapy in liver transplant patients have not been studied. Methods : The effect of transdermal HRT was studied in 33 postmenopausal liver transplant women. The main outcome measure was the change in bone mineral density (BMD) which was measured annually for 2 years. The effect on bone turnover was studied by assessment of the serum aminoterminal propeptide of type I procollagen (PINP). Results : The mean lumbar BMD increased from 0.816 at baseline to 0.858 and to 0.878 g/cm 2 ( P <0.001) after 1 and 2 years of therapy, respectively. The BMD of the femoral neck increased from 0.665 to 0.690 g/cm 2 ( P <0.006). During the first and second years, the mean BMD of the lumbar spine increased by 5.3 and 1.2%, while that of the femoral neck increased by 3.3 and 1.2%. After 2 years of HRT, only one-fifth of the patients had osteoporosis, whereas over half of the women had osteoporosis at baseline. The median serum PINP decreased by 47% at 1 year and remained decreased at 2 years compared with baseline levels. Conclusion : Transdermal HRT decreased the turnover rate of mineralized bone matrix. Transplant women responded with increased BMD, just like healthy postmenopausal women.

Estrogen replacement therapy: implications for postmenopausal women with end-stage renal disease.

Little information is available about either the potential beneficial or harmful effects of estrogen replacement therapy in postmenopausal women with end-stage renal disease. Although evidence supports a role for estrogen replacement therapy in postmenopausal women in the prevention of cardiovascular disease and bone loss, possible improvement in cognitive function, and the relief of menopausal symptoms, these conclusions may not be applicable to patients with end-stage renal disease, since these studies have generally excluded such women. This issue is of considerable importance since cardiovascular causes account for more than 50% of the all-cause mortality in patients with end-stage renal disease. However, estrogen replacement therapy may also have untoward effects in patients with the disease, including an increased risk of dialysis access thrombosis and potentially worsening coronary artery disease in postmenopausal patients. Furthermore, dosing of estrogens needs to be done carefully since renal excretion is important for the elimination of estrogen metabolites. Low dose or alternate day dosing in addition to monitoring estrogen levels may be warranted when prescribing estrogen replacement therapy to women with end-stage renal disease. In this review, it is our objective to analyze the evidence published in the literature so far and to weigh the risks and benefits of estrogen therapy in postmenopausal women with end-stage renal disease.

Postmenopausal hormone use for cardioprotection: what we know and what we must learn.

Coronary heart disease is a highly prevalent and lethal illness for women, particularly in their menopausal years, a fact that fostered interest in hormone use for cardioprotection. Despite the compelling evidence of cardiovascular benefit of estrogen therapy and estrogen and progestin therapy in observational studies of postmenopausal women, and multiple biologically plausible mechanisms for estrogen benefit, precise clinical outcome information from prospective randomized controlled trials is lacking. The only such trial reported, the Heart and Estrogen/Progestin Replacement Study, not only failed to demonstrate cardioprotection, but showed an early adverse outcome in women with documented coronary heart disease who received daily conjugated equine estrogen and medroxy-progesterone acetate. Several large randomized clinical trials of hormone and selective estrogen receptor moderator therapy for primary and secondary prevention are currently underway.

Estrogen Therapy For Menopause

The medical management of menopause continues to be a topic of controversy. Although many of the benefits of estrogen therapy have been well established (treatment of estrogendeficiency symptoms, prevention of osteoporosis, and prevention of coronary heart disease), the potential risks of breast cancer are of great concern. Although many postmenopausal women are candidates for hormone replacement therapy (HRT), many choose not to take it because of fear of breast cancer or concerns about potential side effects and continued menstrual bleeding. Therefore, making choices about potential therapies after menopause can be a difficult one for both women and their health care providers. An important principle of HRT is the notion of short-term versus long-term use, as the goals of both therapy and riskbenefit profiles are different. Although most perimenopausal and postmenopausal women are candidates for short-term HRT (with the exception of those with a history of breast cancer), no general consensus is found r...

Benefits of Estrogen Therapy Extend to the Eye

Benefits of Estrogen Therapy Extend to the Eye

Hormone Replacement Therapy and Gynecologic Cancer

In view of the growing number of postmenopausal women using estrogen replacement therapy for the prevention of acute and chronic consequences of hypoestrogenism, any possible associations between hormone therapy and manifestations of gynecologic cancer are an issue of increasing importance. We reviewed the published literature to evaluate the impact of estrogen replacement therapy on the occurrence of gynecologic malignancies including breast cancer. The tumor growth of ovarian, cervical, vaginal, and vulvar neoplasias is not fundamentally influenced by hormone therapy. However, long-term replacement therapy may be associated with an increased incidence of endometrial hyperplasia and even of neoplasia. This increased risk is related to the duration and cumulative dose of estrogen therapy. Addition of progestin probably reduces the risk of endometrial cancer to that observed in the general population. With regard to the relationship between hormone replacement therapy and the incidence of breast cancer, available epidemiologic data are contradictory. While therapy of less than 5 years appears not to be associated with an increased risk, long-term use may be related to a small but significant increase in the risk of developing breast cancer. It is important to note that the cyclic addition of a progestin to estrogen replacement does not affect this risk. After discontinuation of hormone replacement the increased relative risk returns to that of non-users. In conclusion, when considering estrogen replacement therapy for a postmenopausal woman, a slightly increased risk of developing breast cancer and the need to add progestin for protection of the endome-trium need to be mentioned. Bearing this in mind, the benefits of estrogen therapy in terms of a better quality of life and perhaps of a disease-free prolongation of life justify a wide use of hormonal preparations.

Benefits and risks of estrogen replacement therapy

Estrogen replacement therapy (ERT) has been shown to reduce the risk of cardiovascular disease (CVD) and osteoporosis in postmenopausal women. Studies also indicate a reduced risk of stroke and its consequent mortality among estrogen users, and ERT may also have a role in reducing the risk of Alzheimer's disease and increasing a woman's overall quality of life. On the negative side, some studies show a small duration—related risk of breast cancer with estrogen use and a significant increase in endometrial cancer; the latter is virtually eliminated with the addition of a progestin to the regimen. Although the definitive answer is not yet available recent epidemiologic data suggest no reduction in protection against CVD and bone fracture with the addition of progestin, which is referred to as hormone replacement therapy, as opposed to using estrogen alone. A woman's potential risk associated with ERT or hormone replacement therapy must be weighed against her lifetime risks of developing CVD, stroke, and bone fracture. The reduction in mortality and morbidity rates with hormone use is generally viewed to be substantial and cost-effective. Health care professionals have an important role in shaping their patients' attitudes. Patients need more information from their physicians about the risks and benefits of estrogen therapy.

Maximizing the Benefit of Estrogen Therapy for Prevention of Osteoporosis

AbstractPostmenopausal hormone therapy to prevent osteoporosis is commonly started during menopause and often discontinued within 5–10 years. This approach may preserve bone density during use, but there is evidence that it does not preserve bone density or protect against osteoporotic fractures tha

Management of the menopause.

The management of the peri- or postmenopausal patient, whether symptomatic or asymptomatic, involves a careful assessment of the problems and expectations of each patient and the matching of appropriate treatment to their needs. The effects of the menopause and its treatment on the patient's immediate and long-term health must be taken into account. This may involve consideration of aspects of medical topics as diverse as gynaecological endocrinology, bone metabolism, oncology and cardiology. Although the benefits of oestrogen therapy are well established the response to therapy must be carefully monitored. Vigilance in the monitoring and seeking out of adverse effects both in individuals and populations must continue to ensure that any problems with this form of therapy are detected at the earliest possible stage.

Conjugated estrogens in the treatment of postmenopausal women with hyperparathyroidism.

Fourteen postmenopausal women with mild hyperparathyroidism were given conjugated estrogens. Serum calcium levels became normal and urinary calcium excretion was reduced for up to 2 years in ten patients taking an average dose of 1.25 mg of estrogen daily. Hypercalcemia returned quickly when therapy was interrupted. Estrogen did not systematically alter serum immunoreactive parathyroid hormone or calcitriol levels or urinary excretion of cyclic adenosine monophosphate. Significant reductions in urinary hydroxyproline and serum alkaline phosphatase activity during estrogen therapy indicate that the major effect of therapy was to decrease bone turnover. Iliac crest biopsy specimens taken before estrogen therapy showed normal trabecular bone volume and excessive osteoid seams. Follow-up biopsy specimens were taken from six patients after 1 year on therapy. Bone volume remained stable, but hyperosteoidosis had improved in only one patient. Without understanding the long-term impact of untreated mild hyperparathyroidism on bone, the benefits of estrogen therapy on bone remain uncertain. However, therapy with conjugated estrogens provides sustained control of serum and urine calcium in most women with hyperparathyroidism and is a reasonable alternative in patients who are not surgical candidates.

Estrogens and menopause.

Recent reports suggest that the administration of estrogens to postmenopausal women is associated with an increased risk of developing endometrial cancer. Although the evidence is indirect, it is consistent with the recent introduction into the population of a carcinogen whose primary effect is on the endometrium. Estrogens have often been prescribed for trivial reasons and have been taken for long periods. The median reported length of estrogen use has been 10 years. There is a latency period in the carcinogenic effect so a more frequent incidence of endometrial carcinoma may yet follow. In the meantime, use of estrogens for specific menopausal symptoms is justified. There is less concern in prescribing estrogens for hysterectomized patients. Most emotional problems are better handled by counseling or short-term use of sedatives or tranquilizers. Senile osteoporosis may be benefited by estrogen therapy. Following oophorectomy early in life estrogen treatment may retard onset of osteoporosis but cannot reverse the aging process. Cyclic administration of estrogen use is advised with the lowest effective dose. Vasomotor symptoms require temporary treatment but atrophic vaginitis needs longer therapy. Reevaluation of patients at 6-month intervals at first and then yearly is recommended. A Papanicolaou smear should include material from the endometrial canal. Abnormal bleeding requires investigation. The patient should be informed regarding risks and benefits of estrogen therapy.