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Hyperestrogenism

Hyperestrogenism, also referred to as estrogen excess or high estrogen levels, is a medical condition characterized by abnormally elevated concentrations of estrogen hormones in the body, which can disrupt normal physiological processes, particularly those involving reproduction, and increase the risk of certain health complications.^[1] This imbalance often manifests as estrogen dominance, where estrogen's effects are unopposed by sufficient progesterone, leading to issues such as overgrowth of the uterine lining.^[1] Common causes of hyperestrogenism include overproduction of estrogen by the ovaries or other tissues, such as in conditions like polycystic ovary syndrome (PCOS) or ovarian tumors; external factors like hormone replacement therapy, birth control pills, or exposure to xenoestrogens from environmental sources (e.g., plastics containing BPA); and lifestyle-related contributors including obesity, chronic stress, excessive alcohol consumption, and liver dysfunction that impairs estrogen metabolism.^[1] In rare genetic cases, such as aromatase excess syndrome, increased activity of the aromatase enzyme leads to excessive conversion of androgens to estrogens, resulting in hyperestrogenism from birth or early childhood.^[2] Additionally, certain tumors, like granulosa cell tumors of the ovary, can autonomously produce high levels of estrogen, contributing to the condition.^[3] Symptoms of hyperestrogenism vary by sex, age, and underlying cause but frequently include irregular menstrual cycles with unpredictable timing, heavy or light bleeding, and breast tenderness or fibrocystic changes in women; in men, it may present with gynecomastia (enlarged breast tissue), erectile dysfunction, or infertility.^[1] Both sexes can experience weight gain, fatigue, mood disturbances, and headaches due to hormonal disruption.^[1] In children or adolescents with genetic forms like aromatase excess syndrome, symptoms may include premature breast development (thelarche), accelerated bone age, short stature in adulthood, and irregular menstruation in females, while males might show gynecomastia and hypogonadism.^[2] Diagnosis typically involves blood tests to measure estrogen levels, such as estradiol (the primary form during reproductive years), alongside evaluations of related hormones like progesterone and androgens to identify imbalances or underlying disorders.^[1] Management focuses on addressing the root cause, often through lifestyle modifications like weight loss, a high-fiber diet, stress reduction, and avoiding estrogenic environmental exposures; medications such as aromatase inhibitors (e.g., anastrozole) or selective estrogen receptor modulators may be prescribed to lower estrogen activity.^[1] In severe or genetic cases, surgical intervention for tumors or specialized endocrine therapy is considered.^[2] Untreated hyperestrogenism heightens risks for estrogen-sensitive cancers, including endometrial and breast cancer, underscoring the importance of early detection and intervention.^[1]

Definition and Background

Definition

Hyperestrogenism is a medical condition characterized by an excessive amount of estrogenic activity in the body, resulting from overproduction or impaired metabolism of estrogens, which disrupts normal physiological processes. This state is typically identified through elevated serum estradiol concentrations beyond established reference ranges, such as exceeding 350 pg/mL during the follicular phase in non-pregnant females or surpassing 50 pg/mL in adult males.^[4]^[5] It is important to distinguish hyperestrogenism from estrogen dominance, where estrogen levels are normal but appear relatively elevated due to insufficient progesterone, whereas hyperestrogenism involves an absolute increase in total estrogen concentrations.^[1]^[6] The condition was first recognized in the context of estrogen-secreting tumors in the early 20th century, with the initial report of a feminizing adrenocortical carcinoma appearing in 1919.^[7] Its modern understanding within endocrine oncology emerged in the mid-20th century, including early therapeutic investigations published in 1951.^[8] Clinically, hyperestrogenism may arise from benign or malignant etiologies and necessitates urgent diagnostic assessment to exclude serious underlying pathology, such as neoplasms.^[9]

Normal Estrogen Physiology

Estrogens are a group of steroid hormones primarily including estradiol (E2), estrone (E1), and estriol (E3), with estradiol being the most potent form responsible for the majority of estrogenic effects in the body.^[10] Estrone serves as a weaker estrogen, often produced through peripheral conversion, while estriol is the least potent and predominates during pregnancy.^[10] Estrogen biosynthesis occurs mainly in the ovaries through the action of the enzyme aromatase, which converts androgens such as testosterone and androstenedione into estrogens.^[10] Additional production takes place in the adrenal glands and adipose tissue, where aromatase activity facilitates local estrogen synthesis from circulating precursors.^[10] This process is tightly regulated by the hypothalamic-pituitary-ovarian (HPO) axis: gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn promote ovarian estrogen production; estrogens exert negative feedback on the axis to maintain homeostasis, with positive feedback occurring at mid-cycle to trigger ovulation.^[10] In females, estrogens play key roles in regulating the menstrual cycle by stimulating follicular development, endometrial proliferation, and ovulation through interactions with FSH and LH.^[10] They also maintain bone density by inhibiting osteoclast activity and promoting osteoblast function, provide cardiovascular protection via vasodilation and lipid modulation, and drive the development of secondary sexual characteristics such as breast growth and fat distribution during puberty.^[10] In males, estrogens, present at lower levels, support spermatogenesis by influencing germ cell maturation and fluid reabsorption in the testes via estrogen receptors α and β, and contribute to bone health by regulating bone mineral density and epiphyseal closure.^[11] Normal serum estradiol levels vary by sex, age, and reproductive phase. In premenopausal women, levels range from 20-350 pg/mL during the follicular phase and 30-450 pg/mL during the luteal phase.^[12] In adult men, estradiol levels typically fall between 10-50 pg/mL.^[11] Postmenopausal women exhibit significantly lower levels, often below 20 pg/mL, reflecting diminished ovarian production, with further variations influenced by age and body mass.^[13]

Epidemiology

Prevalence and Incidence

The prevalence and incidence of hyperestrogenism vary widely depending on the underlying cause and population studied. Cases attributable to estrogen-secreting tumors, such as ovarian granulosa cell tumors, are rare, with an estimated annual incidence of less than 1 per 100,000 individuals.^[14] These tumors represent approximately 2-5% of all ovarian malignancies and are a primary driver of clinically significant tumor-related cases.^[15] The condition predominantly affects females, accounting for over 90% of diagnosed tumor-related cases, with a peak incidence in those aged 40-70 years, particularly peri- and postmenopausal women where the mean age at diagnosis for adult granulosa cell tumors is around 50 years.^[14] In males, hyperestrogenism is less common but frequently associated with advanced liver cirrhosis, where prevalence reaches 40-70% depending on disease severity, as elevated estradiol levels occur in up to 47% of cirrhotic men due to impaired hepatic estrogen metabolism.^[16]^[17] In obese populations, prevalence is notably higher. Data from 2025 indicate that hyperestrogenism affects 19% of men with normal BMI but increases to 42% in those with grade III obesity.^[18] Similarly, in postmenopausal women with obesity, elevated estrogen levels are common due to increased peripheral aromatization of androgens in adipose tissue.^[19] Globally, incidence of estrogen-secreting ovarian tumors varies, with higher reported rates in developing regions due to delayed endocrine screening and limited access to diagnostic tools; age-standardized rates for such tumors range from 0.58 to 1.6 per 100,000 women worldwide.^[14] Many cases of mild hyperestrogenism remain undiagnosed, as routine estrogen level screening is not standard in asymptomatic populations, leading to potential underreporting of subclinical elevations.^[1]

Risk Factors

Risk factors for hyperestrogenism can be broadly categorized into non-modifiable and modifiable factors, with lifestyle choices also playing a significant role in susceptibility. Non-modifiable factors include genetic predispositions, such as aromatase excess syndrome, a rare genetic disorder caused by gain-of-function mutations leading to overexpression of the aromatase enzyme and resultant excessive estrogen production.^[20] Age is also non-modifiable, particularly in postmenopausal women, where ovarian estrogen production ceases, but endogenous levels can rise due to increased peripheral aromatization of androgens in adipose tissue, especially in those with higher body fat.^[21] Modifiable risk factors encompass conditions like obesity, where excess adipose tissue enhances aromatase activity, converting androgens to estrogens and elevating circulating levels.^[1] Chronic liver disease, such as cirrhosis, impairs estrogen metabolism and clearance, leading to accumulation and hyperestrogenemia, particularly in males.^[22] Environmental exposures to xenoestrogens, synthetic compounds mimicking estrogen found in plastics (e.g., bisphenol A), further contribute by binding to estrogen receptors and disrupting hormonal balance.^[23] Lifestyle factors that heighten risk include high-fat diets, which correlate with elevated serum estrone levels through enhanced estrogen synthesis.^[24] Excessive alcohol consumption interferes with liver metabolism, reducing estrogen breakdown and increasing levels.^[25] In males, the use of anabolic-androgenic steroids promotes aromatization of excess androgens to estrogens, often resulting in gynecomastia and other hyperestrogenic effects.^[26] Recent research highlights an emerging link between endocrine-disrupting chemicals (EDCs) in consumer products, such as plastics and personal care items, and heightened susceptibility to hormonal imbalances, including estrogen excess.^[27] Addressing modifiable factors like weight management, dietary adjustments, and limiting environmental exposures offers key opportunities for prevention.

Causes

Endogenous Causes

Endogenous causes of hyperestrogenism arise from internal physiological or pathological processes that lead to excessive estrogen production or reduced clearance within the body. These can be broadly categorized into tumor-related, non-tumorous, pregnancy-related, and genetic origins. Tumor-related causes are prominent, with estrogen-secreting ovarian granulosa cell tumors being the most common, accounting for approximately 70% of sex cord-stromal tumors (a subset of ovarian neoplasms). These tumors, derived from sex cord-stromal cells, directly produce estradiol, often leading to symptoms like endometrial hyperplasia. In males, Leydig cell tumors of the testis can secrete estrogen either directly or via peripheral conversion of androgens, resulting in feminization syndromes such as gynecomastia. Adrenal adenomas, though rarer, may also autonomously produce estrogens, particularly in postmenopausal women or prepubertal individuals, contributing to isosexual precocious puberty or other estrogen excess manifestations. Non-tumorous causes include polycystic ovary syndrome (PCOS), where peripheral conversion of androgens to estrogens in adipose tissue elevates circulating levels, making it a hyperestrogenic and hyperandrogenic condition. Liver cirrhosis impairs hepatic conjugation and clearance of estrogens, leading to their accumulation and an increased estrogen-to-androgen ratio, which is commonly observed in affected males. Pregnancy-related endogenous hyperestrogenism is rare and typically transient, as seen in gestational trophoblastic disease, where abnormal trophoblastic proliferation can elevate estrogen production rates, mimicking exaggerated pregnancy hormone dynamics. Genetic causes encompass rare disorders like aromatase excess syndrome, an autosomal dominant condition characterized by gain-of-function mutations promoting excessive extraglandular aromatization of androgens to estrogens, resulting in lifelong elevated levels and associated feminization.

Exogenous Causes

Exogenous causes of hyperestrogenism involve the introduction of estrogenic compounds or stimuli from external sources, leading to elevated estrogen activity or levels in the body. These factors can mimic or supplement endogenous estrogen, potentially disrupting hormonal balance and contributing to clinical manifestations of excess estrogen signaling. Pharmacological interventions are a primary source of exogenous hyperestrogenism. Overuse of hormone replacement therapy (HRT), particularly estrogen-containing formulations, can result in supraphysiological estrogen levels, especially during initial treatment phases or with excessive dosing.^[1] Oral contraceptives with high doses of ethinylestradiol, a synthetic estrogen, introduce potent exogenous estrogenic activity that may elevate overall hormone exposure and mimic hyperestrogenic states, although they typically suppress endogenous production.^[28] Tamoxifen, used in breast cancer treatment, acts as a partial estrogen receptor agonist in certain tissues, potentially inducing ovarian hyperstimulation and subsequent hyperestrogenism, particularly in premenopausal women, with studies showing increased serum estrogen levels during therapy.^[29] Environmental exposures contribute to exogenous estrogenic effects through compounds that bind to estrogen receptors. Phytoestrogens, such as isoflavones found in soy-heavy diets, exert weak estrogenic activity by mimicking estrogen and may lead to hyperestrogenism-like effects in susceptible individuals with high intake, though moderate consumption generally does not significantly alter serum estrogen levels.^[30] Xenoestrogens from pesticides like DDT residues and plastics containing bisphenol A (BPA) act as endocrine disruptors, binding to estrogen receptors and promoting estrogenic signaling that can contribute to excess estrogen activity, with BPA shown to enhance or mimic endogenous estrogen effects in cellular models.^[31] Iatrogenic causes arise from medical procedures, notably ovarian stimulation in fertility treatments. Protocols using gonadotropins to induce multiple follicle development often result in transient spikes in estrogen levels, with serum estradiol exceeding 3,500–5,000 pg/mL commonly associated with ovarian hyperstimulation syndrome (OHSS), a condition characterized by hyperestrogenism and vascular permeability changes.^[32]

Pathophysiology

Mechanisms of Excess Estrogen

Hyperestrogenism arises primarily through overproduction pathways that elevate circulating estrogen levels. A key mechanism involves heightened aromatase activity, the enzyme encoded by the CYP19A1 gene, which catalyzes the conversion of androgens such as testosterone and androstenedione into estrogens like estradiol and estrone. This process occurs predominantly in peripheral tissues, and excessive aromatase expression, as seen in conditions like aromatase excess syndrome, results in supraphysiological estrogen production.^[20] Additionally, elevated estrogens exert negative feedback on the hypothalamic-pituitary-gonadal axis, suppressing the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and subsequently reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion from the anterior pituitary. This feedback inhibition further disrupts normal gonadal function, perpetuating the estrogen excess by limiting androgen production.^[33] At the cellular level, excess estrogens lead to overstimulation of estrogen receptors (ERα and ERβ), nuclear receptors that function as ligand-activated transcription factors. Upon binding estradiol, these receptors dimerize, translocate to the nucleus, and bind estrogen response elements (EREs) in target gene promoters, thereby altering gene transcription in tissues such as the endometrium, breast, and bone. In the endometrium, for instance, ERα overstimulation promotes uncontrolled proliferation of glandular and stromal cells by upregulating genes involved in cell cycle progression, such as cyclin D1 and c-Myc, which can contribute to tissue hyperplasia.^[34] ERβ, while often counter-regulatory to ERα, can also be affected, leading to imbalanced signaling that amplifies proliferative responses in estrogen-sensitive tissues.^[35] Metabolic disruptions further exacerbate estrogen excess by impairing its inactivation and enhancing peripheral synthesis. In the liver, cytochrome P450 enzymes, particularly CYP3A4 and CYP1A2, hydroxylate estradiol to form less active metabolites like 2-hydroxyestradiol, facilitating its excretion via conjugation and biliary/fecal elimination. Impaired hepatic CYP450 function, due to genetic variants or liver disease, reduces this inactivation capacity, allowing unmetabolized estrogen to accumulate in circulation.^[36] Concurrently, adipose tissue serves as a major site for peripheral estrogen conversion through aromatase-mediated transformation of adrenal and gonadal androgens, with obesity amplifying this process due to increased fat mass and inflammatory signals that upregulate CYP19A1 expression.^[19] In males, hyperestrogenism manifests through an aromatization imbalance that skews the testosterone-to-estrogen ratio toward estrogen dominance. Excessive conversion of testosterone to estradiol in adipose and other extragonadal tissues depletes available androgens, mimicking hypogonadism by reducing spermatogenesis and Leydig cell function via suppressed LH-driven testosterone synthesis. This shift not only lowers total and free testosterone levels but also promotes estrogen-mediated effects like gynecomastia and fat redistribution, further fueling peripheral aromatization in a vicious cycle.^[37]

Associated Conditions

Hyperestrogenism is frequently associated with reproductive conditions that rely on estrogen for proliferation and maintenance. Endometriosis involves the ectopic growth of endometrial-like tissue, which is stimulated by elevated estrogen levels that promote lesion expansion and inflammation.^[38] Uterine fibroids, also known as leiomyomas, exhibit estrogen-dependent growth, with excess estrogen enhancing tumor development through receptor-mediated signaling in uterine smooth muscle cells.^[39] These factors contribute to infertility, particularly via anovulation, as chronic high estrogen disrupts follicular maturation and ovulation in conditions like polycystic ovary syndrome.^[40] In oncologic contexts, hyperestrogenism heightens the risk of endometrial disorders, including hyperplasia that can progress to cancer, with prolonged unopposed estrogen exposure linked to an odds ratio of 3.0 for endometrial cancer development.^[41] This risk stems from estrogen's mitogenic effects on endometrial cells, leading to atypical hyperplasia in susceptible women.^[42] Furthermore, excess estrogen promotes breast cancer progression in individuals with estrogen receptor-positive tumors by augmenting cell proliferation and inhibiting apoptosis.^[43] Metabolically, estrogen dominance—characterized by relative or absolute excess estrogen—contributes to insulin resistance, a key precursor to type 2 diabetes, through altered glucose uptake and lipid metabolism in adipose and hepatic tissues.^[44] This association is evident in hyperestrogenic states linked to obesity, where elevated estrogen exacerbates insulin signaling impairments.^[45] Hyperestrogenism also correlates with thyroid dysfunction, as excess estrogen elevates thyroxine-binding globulin levels, reducing free thyroid hormone availability and potentially inducing hypothyroid-like states.^[46] As of 2025, emerging research highlights associations between hyperestrogenism and autoimmune diseases, such as systemic lupus erythematosus (SLE), where estrogen modulates immune responses by enhancing B-cell activity and autoantibody production.^[47] In SLE, estrogen signaling via receptors on immune cells promotes proinflammatory cytokine release, increasing disease flares in affected individuals.^[48] These comorbidities share pathways of estrogen-mediated cellular proliferation and immune dysregulation outlined in the mechanisms of excess estrogen.

Signs and Symptoms

Symptoms in Females

Hyperestrogenism in females manifests primarily through disruptions in reproductive function and systemic effects attributable to estrogen's overstimulation of target tissues. Common presentations include menstrual irregularities stemming from unopposed endometrial proliferation, such as irregular or heavy menstrual bleeding, breakthrough bleeding, and, in some cases, secondary amenorrhea following prolonged estrogen exposure without adequate progesterone opposition. These changes occur because excess estrogen promotes endometrial hyperplasia, leading to unpredictable shedding and increased bleeding volume.^[49]^[1]^[50] Breast-related symptoms are frequent, with tenderness and swelling resulting from estrogen-induced ductal and lobular proliferation, often exacerbating pre-existing fibrocystic changes. In more pronounced cases, such as those involving significant estrogen excess from ovarian or adrenal sources, breast enlargement may occur due to glandular tissue hypertrophy. These effects differ from male presentations, where gynecomastia predominates without the cyclical tenderness seen in females.^[51]^[52]^[1] Systemic symptoms extend beyond reproductive organs, including weight gain particularly in the hips and thighs from estrogen's role in fat distribution and fluid retention. Fatigue, headaches, and mood disturbances such as anxiety or depressive episodes are also reported, linked to estrogen's influence on neurotransmitter modulation and central nervous system sensitivity.^[50]^[51]^[53]^[54] Over the long term, hyperestrogenism can accelerate the growth of uterine fibroids, as estrogen acts as a mitogen for leiomyoma cells, potentially leading to increased pelvic pressure or pain. Additionally, altered vaginal ecology from hormonal imbalance may result in increased discharge, often watery or mucoid, due to enhanced cervical mucus production.^[50]^[55]^[56]^[57]

Symptoms in Males

In males, hyperestrogenism manifests primarily through feminizing effects on the body due to the imbalance between elevated estrogen levels and relatively suppressed androgens, leading to disruptions in secondary sexual characteristics and reproductive function. This condition often arises from endogenous overproduction, such as in aromatase excess syndrome, or exogenous sources, resulting in a range of symptoms that can significantly impact quality of life.^[58]^[59] A hallmark symptom is gynecomastia, characterized by the benign proliferation of glandular breast tissue, which develops due to increased estrogen activity stimulating mammary gland growth. This enlargement is often bilateral and may be tender or painful, particularly during the active phase of tissue development in adolescence or adulthood. In severe instances, such as those associated with estrogen-secreting tumors, the gynecomastia can be pronounced and accompanied by additional feminizing features like sparse facial hair or a higher-pitched voice.^[60]^[61]^[20] Reproductive symptoms are prominent and include erectile dysfunction, diminished libido, and infertility, stemming from estrogen's suppressive effects on the hypothalamic-pituitary-gonadal axis, which reduces gonadotropin release and subsequently impairs testosterone production and spermatogenesis. Elevated estradiol levels have been independently linked to increased severity of erectile dysfunction and orgasmic impairment, while excess estrogen can lead to testicular atrophy and oligospermia, contributing to subfertility in affected men. These effects are exacerbated in conditions like obesity-related hyperestrogenism, where infertility rates are notably higher due to the altered hormonal milieu.^[62]^[11]^[63] Systemically, males with hyperestrogenism may experience fatigue, emotional lability such as mood swings or irritability, and an elevated risk of osteoporosis due to the resultant androgen deficiency promoting bone resorption despite estrogen's general protective role on bone density. These symptoms overlap with some non-reproductive effects seen in females, such as fatigue, but are contextualized differently in male physiology.^[64]^[65]^[61] Unique to male physiology, increased aromatase activity in adipose tissue—particularly in obesity—drives secondary hypogonadism by converting androgens to estrogens, perpetuating a cycle of low testosterone and further estrogen elevation. Recent reports from 2023-2025 have highlighted estrogen-prostate interactions, suggesting that excess estrogen may reprogram prostate cell metabolism, potentially increasing the risk of prostate hyperplasia or cancer progression through estrogen receptor signaling.^[66]^[67]

Diagnosis

Clinical Assessment

The clinical assessment of suspected hyperestrogenism begins with a detailed patient history to identify potential etiologies and associated risks. Clinicians inquire about menstrual irregularities, including heavy, prolonged, or irregular bleeding, which may signal estrogen excess influencing endometrial proliferation. Medication history is reviewed, encompassing hormone replacement therapies, selective estrogen receptor modulators, or other pharmaceuticals that could elevate estrogen levels. Family history of estrogen-sensitive cancers, such as breast or endometrial carcinoma, is elicited, as genetic predispositions may contribute to hyperestrogenic states. Potential environmental exposures to endocrine-disrupting chemicals, like xenoestrogens from plastics or pesticides, are explored for their estrogen-mimicking effects. The onset, duration, and progression of symptoms, such as fatigue or breast tenderness, are documented to gauge acuity and chronicity. Physical examination focuses on identifying manifestations of estrogen excess and underlying pathology. Palpation of the breasts and abdomen is performed to detect masses, such as fibroadenomas or ovarian tumors, that may produce excess estrogen. Secondary sexual characteristics are evaluated, including deviations in Tanner staging for breast development, which can indicate accelerated pubertal progression due to estrogen influence. Body mass index (BMI) is calculated to assess obesity, as adipose tissue aromatizes androgens to estrogens, exacerbating hyperestrogenism. Key red flags during assessment include sudden weight gain or loss, potentially reflecting metabolic disruptions from hormonal imbalance. Unexplained infertility, particularly in the absence of virilizing features like hirsutism, raises suspicion for estrogen-mediated ovulatory dysfunction. These findings prompt urgent evaluation to rule out serious causes. In line with 2025 clinician and patient perspectives on endocrinology care, telehealth is emphasized for initial screening of endocrine symptoms, including those linked to post-COVID hormonal alterations, facilitating broader access to history collection before in-person exams. If clinical suspicion persists, laboratory testing is pursued for confirmation.

Laboratory and Imaging Tests

Diagnosis of hyperestrogenism relies on laboratory tests to confirm elevated estrogen levels and evaluate associated hormonal disruptions, typically initiated based on clinical suspicion. The primary blood test is measurement of serum estradiol (E2), the most potent estrogen, which is elevated in hyperestrogenic states; levels are assessed via immunoassay or liquid chromatography-mass spectrometry for accuracy, with normal ranges varying by age, sex, and menstrual phase (e.g., >200 pg/mL in postmenopausal women may indicate excess).^[68]^[69] Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels are often suppressed due to negative feedback from high estrogen, while testosterone and progesterone are measured to assess relative imbalances, such as low testosterone in males with gynecomastia or irregular progesterone in females with endometrial effects.^[1]^[70] For suspected ovarian granulosa cell tumors, a common cause of endogenous hyperestrogenism, tumor markers like inhibin B are highly specific and sensitive, with elevated levels (>100 pg/mL) supporting diagnosis and monitoring recurrence.^[71]^[72] Additional laboratory evaluations include sex hormone-binding globulin (SHBG) to determine free estrogen bioavailability, as estrogen excess upregulates SHBG, potentially altering active hormone fractions.^[73] Liver function tests, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are recommended to rule out hepatic impairment, which can reduce estrogen metabolism and contribute to elevated circulating levels.^[74] Imaging studies target potential sources of excess estrogen. Pelvic ultrasound is the initial modality for detecting ovarian masses, such as granulosa cell tumors, appearing as solid or multilocular-solid lesions with vascularity on Doppler.^[72]^[75] For adrenal etiologies, computed tomography (CT) or magnetic resonance imaging (MRI) evaluates tumors, with MRI preferred for its soft-tissue contrast in identifying estrogen-secreting adenomas.^[76] In chronic cases, dual-energy X-ray absorptiometry (DEXA) scan assesses bone mineral density, as prolonged hyperestrogenism may indirectly influence skeletal health through associated conditions.^[77] As of 2025, advances include liquid biopsy for circulating tumor DNA (ctDNA) in suspected malignancies like granulosa cell tumors, enabling non-invasive detection of mutations (e.g., FOXL2) and monitoring without tissue sampling.^[78] AI-assisted ultrasound enhances early adnexal mass detection by analyzing echogenic patterns, achieving high sensitivity (up to 95%) for distinguishing benign from malignant lesions in multicenter validations.^[79]^[80]

Management and Treatment

Medical Treatments

Medical treatments for hyperestrogenism primarily involve pharmacological interventions aimed at reducing estrogen production, blocking its receptor activity, or counteracting its effects, with choices tailored to the underlying cause such as ovarian hyperstimulation, obesity-related aromatase activity, or tumor secretion. These approaches are often preferred initially over invasive options due to their non-surgical nature and potential for reversibility.^[1] Anti-estrogens, including selective estrogen receptor modulators (SERMs) like tamoxifen and raloxifene, work by binding to estrogen receptors in target tissues such as the breast and uterus, thereby blocking estrogen's proliferative effects without altering circulating levels. Tamoxifen, typically dosed at 20 mg daily, is commonly used in cases of gynecomastia associated with hyperestrogenism. Raloxifene, at 60 mg daily, offers similar receptor blockade with a more favorable bone-protective profile but is less versatile for uterine indications.^[81]^[82] Aromatase inhibitors, such as anastrozole, directly suppress estrogen synthesis by inhibiting the aromatase enzyme that converts androgens to estrogens, particularly in adipose tissue or gonadal sources. Anastrozole is administered at 1 mg daily and has demonstrated efficacy in reducing serum estradiol levels by up to 50-70% in men with hyperestrogenemia secondary to testosterone replacement therapy, while also alleviating symptoms like fatigue and sexual dysfunction. This class is especially useful in obesity-related hyperestrogenism, where excess fat amplifies peripheral estrogen production. In genetic conditions like aromatase excess syndrome, lifelong aromatase inhibitors such as anastrozole are used to suppress estrogen production from early childhood.^[83]^[84]^[85]^[2] Progestins provide opposition to estrogen's unopposed actions, particularly in cases of estrogen dominance leading to endometrial overgrowth or irregular bleeding. Micronized progesterone, bioidentical to endogenous forms, is given orally at 200-300 mg daily and effectively induces endometrial secretory changes while minimizing androgenic side effects compared to synthetic progestins. It is preferred for its tolerability in perimenopausal or dominance scenarios, with studies showing reduced hyperplasia risk when balancing elevated estrogen. GnRH agonists, such as leuprolide, suppress pituitary gonadotropin release, thereby decreasing ovarian estrogen production in premenopausal women with hyperestrogenism from functional cysts or hyperthecosis; typical dosing involves monthly depot injections of 3.75 mg, achieving up to 95% reduction in sex hormones.^[86]^[87]^[88]^[89]^[90] Supportive lifestyle interventions complement pharmacotherapy by addressing modifiable contributors to elevated estrogen. Weight loss through diet and exercise can lower aromatase activity in adipose tissue, reducing endogenous estrogen synthesis; for instance, a 5-10% body weight reduction has been associated with normalized estradiol levels in obese individuals. Diets low in xenoestrogens—avoiding plastics, pesticides, and processed foods—minimize environmental estrogen mimics that exacerbate hyperestrogenism, with adherence linked to improved hormonal balance in observational studies.^[1]^[91]^[6]

Surgical Options

Surgical interventions for hyperestrogenism target the underlying sources of excess estrogen production, such as tumors, to achieve definitive resolution of the condition. These procedures are typically considered after medical evaluation confirms a surgically amenable etiology, like hormone-secreting neoplasms, and when conservative management is insufficient or inappropriate. Tumor resection is the cornerstone for estrogen-producing ovarian tumors, such as granulosa cell tumors, where unilateral oophorectomy is preferred to preserve fertility in premenopausal women with unilateral involvement and benign pathology.^[92] Bilateral oophorectomy may be required for bilateral disease, malignancy, or when fertility preservation is not a concern, with laparoscopic techniques minimizing recovery time and complications.^[93] For the rare estrogen-secreting adrenal tumors, such as adrenocortical carcinomas, adrenalectomy provides curative removal, often via minimally invasive approaches to preserve contralateral adrenal function.^[94] Hysterectomy is indicated for endometrial hyperplasia or associated endometrial cancer resulting from chronic unopposed estrogen exposure, particularly in atypical cases where malignancy risk exceeds 20-30%. Laparoscopic or robotic-assisted hysterectomy is favored for its reduced blood loss, shorter hospital stays, and lower infection rates compared to open surgery.^[95] In males with hyperestrogenism-induced gynecomastia, orchiectomy is uncommon but may be performed for rare estrogen-producing testicular tumors like Leydig cell neoplasms.^[96] Mastectomy, often via subcutaneous or endoscopic methods, addresses severe, persistent glandular enlargement unresponsive to other interventions, improving cosmetic and psychological outcomes.^[58]^[97] Advancements in 2025 include widespread adoption of robotic-assisted surgery for these procedures, enhancing precision in pelvic and adrenal access, with reported success rates over 95% for complete benign tumor resection and 3-year overall survival nearing 98% in early-stage cases.^[98]^[99] Postoperative protocols emphasize serial hormone monitoring, including estradiol levels, to confirm normalization and detect any residual or recurrent hyperestrogenism.^[100]

Prognosis and Complications

Long-term Outcomes

In benign cases of hyperestrogenism, such as those arising from non-malignant ovarian tumors like thecomas or functional endocrine disorders, treatment typically leads to favorable outcomes following surgical removal or medical management, with symptom relief often achieved within 3-6 months post-intervention.^[101] Fertility can be restored in many reproductive-age females after addressing the underlying cause, particularly when fertility-preserving surgeries are performed, though outcomes vary based on the duration of exposure and individual ovarian reserve.^[102]^[103] For malignant causes, such as granulosa cell tumors, the 5-year survival rate exceeds 90% when the disease is localized at diagnosis, with overall prognosis remaining favorable due to the indolent nature of these neoplasms.^[104] Recurrence risk stands at approximately 15-20% for early-stage cases, necessitating long-term surveillance for up to 20 years given the potential for late relapse.^[105] In males with hyperestrogenism-induced gynecomastia, aromatase inhibitors achieve reversal or significant reduction in breast tissue in 36-72% of cases, depending on treatment duration and etiology, though chronic conditions like liver cirrhosis may lead to persistent infertility despite intervention.^[106]^[107] Recent advancements as of 2025, including targeted therapies like PARP inhibitors for recurrent granulosa cell tumors, have contributed to improved prognoses, with studies indicating enhanced progression-free survival in relapsed cases compared to pre-2020 standards.^[108] These outcomes are influenced by early intervention and may be compounded by associated complications such as cardiovascular risks.^[109]

Potential Complications

Untreated hyperestrogenism significantly elevates the risk of endometrial cancer progression, with unopposed estrogen exposure associated with a relative risk increase of approximately fourfold compared to non-users.^[110] This heightened risk stems from estrogen's proliferative effects on endometrial tissue, particularly in conditions such as obesity or estrogen-secreting tumors. Additionally, excess estrogen promotes a prothrombotic state, increasing the incidence of cardiovascular events like venous thromboembolism and arterial thrombosis.^[109] In males, untreated hyperestrogenism, often seen in syndromes like Klinefelter's where estrogen levels are relatively elevated alongside testosterone deficiency, contributes to bone loss and osteoporosis, with prevalence rates of osteopenia reaching 25-48% and osteoporosis 6-15%.^[111] Treatment-related complications of hyperestrogenism management include side effects from aromatase inhibitors, such as joint pain (arthralgias) affecting up to 50% of users and accelerated bone loss leading to osteoporosis and fractures.^[112] Surgical interventions, like oophorectomy for estrogen-producing ovarian pathology, carry risks of postoperative infection and immediate induction of surgical menopause, which can exacerbate cardiovascular and skeletal vulnerabilities if not managed with hormone therapy.^[113] Chronic hyperestrogenism may lead to persistent mood disorders, with elevated estrogen levels linked to depressive symptoms in both sexes, potentially through altered neurotransmitter modulation in the brain.^[114] Recent studies indicate that prolonged hyperestrogenism may interfere with thyroid function due to estrogen's effects on thyroid-binding globulin.^[115] To mitigate recurrence and these sequelae, annual follow-up with hormonal assays and imaging is recommended for early detection and intervention. These complications can impact long-term outcomes, as detailed in related sections.

References

[1]
High Estrogen: Causes, Symptoms, Dominance & Treatment
Feb 9, 2022 · Too much estrogen, though, can cause irregular periods and may worsen conditions that affect your reproductive health.
[2]
Aromatase excess syndrome: MedlinePlus Genetics
Apr 1, 2014 · Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females.Missing: hyperestrogenism treatment
[3]
[PDF] Hormones and receptors in endometrial cancer
It is this function that may occur autonomously in women with granulosa cell tumors and lead to a hyperestrogenic state. The classic symptoms associated with a.
[4]
Estradiol - Medscape Reference
Oct 9, 2025 · Reference ranges for serum estradiol · Follicular phase: 20-350 pg/mL · Midcycle peak: 150-750 pg/mL · Luteal phase: 30-450 pg/mL · Postmenopause: ≤ ...
[5]
Medical Definition of HYPERESTROGENISM - Merriam-Webster
The meaning of HYPERESTROGENISM is a condition marked by the presence of excess estrogens in the body.Missing: sources | Show results with:sources<|control11|><|separator|>
[6]
Estrogen Dominance - Whole Health Library - VA.gov
Estrogen dominance is the condition of increased estrogen levels relative to progesterone levels in the body.Missing: hyperestrogenism | Show results with:hyperestrogenism
[7]
Feminizing Adrenocortical Carcinoma: The Source of Estrogen ...
Feminizing ACC was first reported in 1919 in a 26-year-old man who presented with gynecomastia (5). Since then, ~80 cases have been reported, mainly as case ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[8]
Hyperestrogenism and its therapy; preliminary report - PubMed
Hyperestrogenism and its therapy; preliminary report. Am J Obstet Gynecol. 1951 Jan;61(1):183-7. doi: 10.1016/0002-9378(51)90023-3.
[9]
Hyperestrogenism - an overview | ScienceDirect Topics
Hyperestrogenism is defined as a condition characterized by symptoms that lead to prompt investigation and early diagnosis. It often presents with an adnexal ...
[10]
Estrogen Hormone Biology - PMC - NIH
The hormone estrogen is involved in both female and male reproduction, as well as numerous other biological systems including the neuroendocrine, vascular, ...
[11]
Estrogens, Male Reproduction and Beyond - Endotext - NCBI - NIH
Mar 21, 2023 · In adult men, elevated serum estradiol levels induce mild ... In adult men, the normal range of serum estradiol is around 14-43 pg/mL ...
[12]
Estradiol blood test Information | Mount Sinai - New York
Female (premenopausal): 30 to 400 pg/mL (110 to 1468.4 pmol/L); Female (postmenopausal): 0 to 30 pg/mL (0 to 110 pmol/L). Normal value ranges may vary slightly ...Missing: authoritative source<|separator|>
[13]
Menopause - StatPearls - NCBI Bookshelf - NIH
Dec 21, 2023 · An elevated serum FSH (>30 mIU/mL) is an objective indicator of menopause. It is important to remember that pelvic surgeries may elevate FSH ...Missing: luteal | Show results with:luteal
[14]
Granulosa Theca Cell Tumors of the Ovary - StatPearls - NCBI - NIH
Nov 12, 2023 · Granulosa cell tumors are rare ovarian neoplasms derived from sex cords and ovarian mesenchyme with an indolent course and long natural history.Continuing Education Activity · Introduction · Epidemiology · Histopathology
[15]
Prognostic factors of adult granulosa cell tumors of the ovary
Dec 20, 2023 · Adult granulosa cell tumors of the ovary (AGCT) are rare and account for approximately 2%–5% of all ovarian malignancies [1, 2]. AGCT is the ...
[16]
Study of Gonadal Hormones in Males With Liver Cirrhosis and ... - NIH
Jan 21, 2023 · This study aimed to study sex hormones in males with cirrhosis and determine their correlation with prognostic scores.
[17]
[PDF] Exploring Gonadal Functions in Patients With Alcoholic Liver Disease
Nov 6, 2024 · Hormonal analysis indicated hyperestrogenemia in 57.8% (n=26) of fatty liver patients and 70% (n=21) of those with alcoholic hepatitis and ...<|control11|><|separator|>
[18]
Clinical variables in hyperestrogenism and hypogonadism in obese ...
As BMI increased, the incidence of hyperestrogenism rose from 19% in men with normal BMI to 42% in those with grade III obesity. Testosterone deficiency was ...
[19]
Understanding the pathological manifestations of aromatase excess ...
The associated symptoms (small testis, high-pitched voice, sparse facial hair, variably advanced bone age and short adult height) are exclusively related to ...
[20]
BRCA Gene Changes: Cancer Risk and Genetic Testing Fact Sheet
Jul 19, 2024 · The risks of developing breast and ovarian cancer are markedly increased in people who inherit a harmful change in BRCA1 or BRCA2.Missing: hyperestrogenism | Show results with:hyperestrogenism
[21]
Source of Estrogen Production in Postmenopausal Women1
The results suggests that the principal estrogen formed in postmenopausal women is estrone and that it is derived by aromatization of plasma A.
[22]
From liver to hormones: The endocrine consequences of cirrhosis
In males, this condition is due to hyperestrogenism caused by reduced hepatic clearance of estrogen due to portal hypertension, decreased testosterone ...
[23]
Most Plastic Products Release Estrogenic Chemicals: A Potential ...
Background: Chemicals having estrogenic activity (EA) reportedly cause many adverse health effects, especially at low (picomolar to nanomolar) doses in ...
[24]
Fat Intake Is Associated with Serum Estrogen and Androgen ...
These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.
[25]
Alcohol consumption, endogenous estrogen and mammographic ...
Aug 7, 2015 · Alcohol consumption was positively associated with daily endogenous estrogen levels and mammographic density in premenopausal women.Missing: hyperestrogenism | Show results with:hyperestrogenism
[26]
Anabolic Steroid Use and Abuse - Medscape Reference
Dec 5, 2024 · The aromatization of testosterone/AASs to estradiol and related compounds can render many adverse estrogenic effects. The most apparent and ...
[27]
Oral contraceptives cause evolutionarily novel increases in hormone ...
Jun 5, 2017 · Several oral contraceptive pills cause evolutionarily novel increases in hormone exposure and may thereby promote breast cancer risk.Missing: hyperestrogenism | Show results with:hyperestrogenism
[28]
Tamoxifen-induced ovarian hyperstimulation during premenopausal ...
These findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment.
[29]
Soy and phytoestrogens: possible side effects - PMC - NIH
Dec 15, 2014 · Phytoestrogens are present in different edible plants being most abundant in soy; among others, they are used to compensate for estrogen deficiency in ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[30]
Exploring the Biological Activity and Mechanism of Xenoestrogens ...
Although numerous studies indicating the toxic effects of both BPA and DDT, these two xenoestrogens are still being used today. BPA has continued to be used in ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[31]
Value of the serum estradiol level for preventing ovarian ...
In OHSS, there is a marked elevation in estrogen levels, mainly E2, which could be associated with a risk of developing the syndrome.
[32]
https://www.sciencedirect.com/science/article/pii/S0015028203027146
[33]
Estrogen inhibition of LH and FSH secretion: effects of a GnRH ...
The acute inhibitory effects of various doses of estrogen on FSH and LH secretion were examined in cannulated, 2-wk ovariectomized rats. No dose of 17 beta- ...
[34]
Estrogen Receptor Function: Impact on the Human Endometrium
Feb 28, 2022 · Elevated estrogen promotes the expression of ERα and ERβ, which reach their highest levels in the late proliferation phase (97); however, ...Missing: overstimulation | Show results with:overstimulation
[35]
Knockdown of estrogen receptor β increases proliferation and ...
Jul 29, 2019 · In this study, we knocked down expression of ERβ in two endometrial cancer cell lines and observed enhanced proliferation both of ERα-positive ...Missing: overstimulation | Show results with:overstimulation
[36]
Cytochrome P450-mediated metabolism of estrogens and ... - PubMed
Estrogens are eliminated from the body by metabolic conversion to estrogenically inactive metabolites that are excreted in the urine and/or feces.Missing: impaired inactivation
[37]
Obesity, estrogens and adipose tissue dysfunction - PubMed Central
This is known as central obesity, and the excess visceral adiposity leads to an array of cardiovascular disease risk factors known as metabolic syndrome.
[38]
High aromatase activity in hypogonadal men is associated ... - NIH
Men with high aromatase activity are able to maintain a higher BMD despite low circulating testosterone, but they have lower lean and higher truncal fat mass.
[39]
Endometriosis in the era of precision medicine and impact on sexual ...
Aug 29, 2023 · Endometriosis is a common, estrogen-dependent disease wherein tissue similar to the lining of the uterus (endometrium) exists outside its normal ...
[40]
Estrogen Receptors and Signaling in Fibroids: Role in Pathobiology ...
Fibroids are considered estrogen dependent since no prepubertal cases have been described, and tumors tend to regress after menopause and on gonadotropin- ...
[41]
Female infertility: which role for obesity? - PubMed
... hyperestrogenism that contribute to produce anovulation and to reduce endometrial receptivity and, therefore participate to cause infertility. Weight loss ...<|control11|><|separator|>
[42]
Estrogen replacement therapy and endometrial cancer risk - PubMed
Estrogen use significantly increased endometrial cancer risk (adjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.7-5.1).
[43]
Endometrial Cancer Prevention (PDQ®) - NCI
Apr 10, 2025 · Based on solid evidence, unopposed estrogen is associated with an increased risk of endometrial cancer. This excess risk can be eliminated ...
[44]
Estrogens and breast cancer - Annals of Oncology
Nov 7, 2024 · Estrogen may increase breast cancer risk by inducing the progesterone receptor and augmenting progesterone signaling.
[45]
Aromatase up-regulation, insulin and raised intracellular oestrogens ...
Apr 4, 2012 · For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign ...Missing: dominance | Show results with:dominance
[46]
Interplay between insulin resistance and estrogen deficiency as co
Insulin resistance and estrogen deficiency are concomitant disorders with mutual interrelationship. Insulin resistance and the compensatory hyperinsulinemia ...Missing: dominance | Show results with:dominance
[47]
Role of Estrogen in Thyroid Function and Growth Regulation - PMC
Estrogen has a well-known indirect effect on thyroid economy, increasing the thyroxine binding globulin [4], and the need for thyroid hormone in hypothyroid ...Missing: association | Show results with:association
[48]
Exploring Effects of Estrogen Analog Supplementation - PubMed
Dec 10, 2024 · Combined estrogen and progesterone therapy is associated with an increased risk of several autoimmune conditions.
[49]
Estrogen Receptors and Platelet-Activating Acetylhydrolase Activity ...
Jan 27, 2025 · Estrogen promotes lupus in human and mouse models of SLE. In this study, we conducted an in vivo study to investigate the relationship between ...
[50]
Abnormal Uterine Bleeding | AAFP
Oct 1, 1999 · Estrogen breakthrough bleeding occurs when excess estrogen stimulates the endometrium to proliferate in an undifferentiated manner. With ...
[51]
Signs and symptoms of high estrogen - MedicalNewsToday
High estrogen can cause weight gain, heavy periods, and fatigue in females. In males, it can cause infertility and breast tissue growth. Learn more here.
[52]
Signs and Symptoms of High Estrogen - Healthline
Jun 9, 2023 · High levels of estrogen can develop naturally, but too much estrogen can also result from taking certain medications or other health conditions.Causes · Symptoms · Typical levels · Treatment
[53]
Cutaneous manifestations of estrogen excess and deficiency
Dec 13, 2021 · The most commonly encountered cause of estrogen excess is pharmacologic or exogenous use of estrogens for either contraception, treatment of ...
[54]
Estrogen: Hormone, Function, Levels & Imbalances - Cleveland Clinic
Feb 8, 2022 · Estrogen levels naturally fluctuate during your menstrual cycle and decline during menopause. Consistently high or low levels of estrogen may ...Overview · Function · Conditions And Disorders<|control11|><|separator|>
[55]
Estrogen Dominance - AMC - American Medical Center
Oct 30, 2024 · Estrogen dominance is a condition in which estrogen levels in the body are increased. Signs and symptoms can include but are not limited to, full and tender ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[56]
Uterine Fibroids in Menopause and Perimenopause - PMC
Uterine fibroids (UFs) are benign tumors that arise from a single genetically altered mesenchymal stem cell under the influence of gonadal hormones.
[57]
Fibroid Tissue Discharge: Passing and More - Healthline
Mar 9, 2021 · Fibroids can also increase the amount of vaginal discharge you have. This discharge is typically watery but may appear pink if there's also ...
[58]
High Estrogen vs Low Estrogen Symptoms: What They Mean ... - Evvy
Oct 5, 2025 · Symptoms of high estrogen · Irregular periods or heavy bleeding · Breast tenderness or swelling · Increased vaginal discharge · Mood swings, ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[59]
The PCOS Phenotypes in Unselected Populations (P-PUP) study
Jul 15, 2025 · Hyperandrogenism is an essential PCOS diagnostic feature and manifests clinically as hirsutism, acne and androgenic alopecia. Acne and ...Selection Of Studies · Data Harmonization And... · Author Information
[60]
Gynecomastia: Etiology, Diagnosis, and Treatment - Endotext - NCBI
Jan 6, 2023 · Gynecomastia occurs in one third of cases of Sertoli cell tumors, presumably due to increased estrogen production (26). Sertoli cell tumors ...
[61]
Aromatase excess syndrome: MedlinePlus Genetics
Apr 1, 2014 · Increased estrogen in females can cause symptoms such as irregular menstrual periods and short stature.Missing: hyperestrogenism | Show results with:hyperestrogenism
[62]
Enlarged breasts in men (gynecomastia) - Symptoms and causes
Oct 26, 2023 · Estrogen levels that are too high or are out of balance with testosterone levels can cause gynecomastia. Gynecomastia in infants. More than half ...
[63]
Gynecomastia: Pathophysiology, Evaluation, and Management - PMC
Gynecomastia, defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activityClinical Manifestations And... · Diagnostic Approach · Cme Questions About...
[64]
Hyperestrogenism is associated with sexual function impairment in ...
Jun 3, 2023 · Circulating hormones were measured in every patient. Hyperestrogenism was defined as estradiol levels >42.6 pg/mL (Tan et al., 2015). ...
[65]
The role of estradiol in male reproductive function - PMC
Feb 23, 2016 · Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts ...
[66]
Benign Feminizing Adrenal Tumor in an Adult Male - PMC
Estrogen production can be solitary but is more commonly accompanied by the production of other adrenocortical hormones.Missing: hyperestrogenism | Show results with:hyperestrogenism<|control11|><|separator|>
[67]
Estrogens and bone health in men - PubMed - NIH
We found that estrogen played the major role in regulating bone resorption in these men, and that both estrogen and testosterone were important in maintaining ...Missing: excess | Show results with:excess
[68]
Male Obesity-related Secondary Hypogonadism – Pathophysiology ...
In obese individuals, enhanced aromatase enzymes produced by adipose tissue reduce the testosterone and increase the oestrogen hormones. Testosterone deficiency ...
[69]
The Pros and Cons of Estrogens in Prostate Cancer - NIH
This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens.
[70]
Estrogen Levels Test: MedlinePlus Medical Test
Jul 30, 2025 · An estrogen test measures the level of estrogens in your blood or urine. Estrogen levels affect fertility, pregnancy, bone health, and more.<|control11|><|separator|>
[71]
Estradiol blood test - UCSF Health
Aug 23, 2023 · An estradiol test measures the amount of a hormone called estradiol in the blood. Estradiol is one of the main types of estrogens.
[72]
EEST - Overview: Estradiol, Serum - Mayo Clinic Laboratories
Irregular or absent menstrual periods with normal or high E2 levels (and often high estrone: E1 levels) are indicative of possible polycystic ovarian syndrome, ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[73]
Role of inhibin B in detecting recurrence of granulosa cell tumors of ...
Apr 23, 2021 · Inhibin B is a sensitive and specific marker for adult-type granulosa cell tumors of the ovary that may be used during follow-up for detection of recurrences.
[74]
Granulosa-Theca Cell Tumors Workup - Medscape Reference
Nov 14, 2024 · Although inhibin A and inhibin B levels can both be elevated in patients with granulosa cell tumors, inhibin B level is usually elevated in ...Laboratory Studies · Imaging Studies · Histologic Findings
[75]
SHBG1 - Overview: Sex Hormone-Binding Globulin, Serum
Diagnosis and follow-up of women with signs or symptoms of androgen excess (eg, polycystic ovarian syndrome and idiopathic hirsutism)Missing: hyperestrogenism | Show results with:hyperestrogenism
[76]
The Influence of Sex Hormones in Liver Function and Disease - PMC
... Impaired estrogen signaling is associated with liver pathology in males. Low estrogen promotes liver disease via impaired glucose metabolism. High levels of ...Missing: inactivation hyperestrogenism
[77]
Imaging of gynecological disease (3): clinical and ultrasound ...
Mar 13, 2008 · At ultrasound examination, most GCTs are large multilocular–solid masses with a large number of locules, or solid tumors with heterogeneous echogenicity of the ...
[78]
Functioning Ovarian Tumors: Direct and Indirect Findings at MR ...
Oct 1, 2004 · It is well known that metastatic ovarian tumors often have androgen-producing stroma and that mucinous cystadenoma sometimes produces estrogens.<|control11|><|separator|>
[79]
Dual-Energy X-Ray Absorptiometry - StatPearls - NCBI Bookshelf
A DEXA scan is typically performed using a C-arm with an x-ray source that allows for variable photon energy levels, a collimator, a detector, and associated ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[80]
Liquid biopsy in cancer: current status, challenges and future ...
Dec 2, 2024 · Liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on.
[81]
International multicenter validation of AI-driven ultrasound detection ...
Jan 2, 2025 · Deep learning has shown promising results in the detection of ovarian cancer in ultrasound images; however, external validation is lacking. In ...
[82]
Hybrid artificial intelligence echogenic components‐based ... - NIH
Jul 15, 2025 · A novel hybrid AI/CADx echogenic components‐based ultrasound imaging pipeline can distinguish between malignant and benign adnexal masses with strong ...
[83]
Tamoxifen: What to Expect, Side Effects, and More - Breastcancer.org
Feb 28, 2025 · Tamoxifen blocks the effects of estrogen on hormone receptor-positive breast cancer cells by attaching to the estrogen receptors on the cells.Missing: hyperestrogenism | Show results with:hyperestrogenism
[84]
Managing the side effects of tamoxifen and aromatase inhibitors
Aug 18, 2025 · Tamoxifen (as well as raloxifene) has antiestrogenic activity in breast tissue, reducing epithelial cell proliferation [1,2].
[85]
Treatment of estrogen levels in the management of hypogonadism
Feb 8, 2020 · Anastrozole was the most common medication prescribed for symptomatic hyperestrogenemia (62.3%), but starting doses varied significantly, from 1mg weekly to 1 ...
[86]
Aromatase inhibitors in men: effects and therapeutic options - PMC
Estrogen excess in turn has been associated with premature closure of the epiphyses, gynecomastia and low gonadotropin and testosterone levels. Lowering ...<|control11|><|separator|>
[87]
High estrogen in men after injectable testosterone therapy - PubMed
Testosterone replacement improves quality of life and is aromatized in men in adipose tissues to estrogen. Hyperestrogenism is believed to be harmful to male ...
[88]
Medroxyprogesterone Acetate Antagonizes the Effects of Estrogen ...
Like other progestogens, MPA counteracts the proliferative effects of estrogen treatment in the uterus and protects against endometrial hyperplasia (1, 2).
[89]
Progesterone, Obesity, and the Prevention of Endometrial Cancer
We propose that endometrial cancer can be prevented in the obese population by treatment with progesterone, which counters the effects of excess estrogen.Missing: dominance | Show results with:dominance
[90]
Micronized progesterone: clinical indications and comparison with ...
Oral micronized progesterone has widespread clinical potential, particularly for the treatment of secondary amenorrhea and dysfunctional premenopausal bleeding.
[91]
Postmenopausal Hyperandrogenism: Evaluation and Treatment ...
In a 2018 study by Elhassan and colleagues, hyperthecosis accounted for up to 9.3% of all cases of postmenopausal hyperandrogenism in 1205 consecutively ...
[92]
Gonadotropin Releasing Hormone (GnRH) Analogues - NCBI - NIH
Mar 20, 2018 · Leuprolide, goserelin, triptorelin and histrelin are considered GnRH agonists, whereas degarelix acts predominantly as an antagonist.Missing: hyperestrogenism | Show results with:hyperestrogenism
[93]
The Effects of Diet and Exercise on Endogenous Estrogens ... - NIH
Sep 20, 2021 · In addition, other risk factors have an association with estrogen exposure within the body, such as the early onset of menstruation (<12 years) ...Missing: hyperestrogenism | Show results with:hyperestrogenism
[94]
ELEGANT: Elacestrant versus standard endocrine therapy (ET) in ...
May 28, 2025 · Elacestrant is a next-generation oral SERD that provides a novel mechanism of action that has shown both SERD (degradative) and SERM (partial ...
[95]
Elacestrant in Women with Estrogen Receptor-Positive and HER2 ...
Apr 1, 2025 · Elacestrant has shown significantly prolonged progression-free survival compared with standard-of-care endocrine therapy in estrogen receptor-positive (ER- ...
[96]
Elacestrant Shows Greater Benefit in Endocrine-Sensitive Breast ...
Jan 30, 2025 · The study showed that the oral selective estrogen receptor degrader (SERD) provided a significant improvement in progression-free survival compared with ...
[97]
Ovarian high-grade serous carcinoma with estrogenic ... - NIH
In addition, although the precise mechanism is unknown, epithelial ovarian cancers can be associated with elevated serum estrogen levels on rare occasions.
[98]
Oophorectomy - StatPearls - NCBI Bookshelf - NIH
Feb 22, 2025 · Oophorectomy is the surgical removal of one or both ovaries. This procedure may be performed to treat ovarian pathology, such as neoplasms, for risk reduction.
[99]
Estrogen-secreting adrenocortical carcinoma - PMC - NIH
We report a case of estrogen-secreting adrenocortical carcinoma in a 53-year-old man who presented with abdominal discomfort and gynecomastia.
[100]
Endometrial Hyperplasia - StatPearls - NCBI Bookshelf - NIH
Apr 30, 2024 · If fertility preservation is not desired, total hysterectomy is generally recommended for women with atypical endometrial hyperplasia due to ...
[101]
Testicular Cancer - Uw Urology - University of Washington
In the rarer non-germ cell testicular cancers, Leydig cell tumors produce androgens (male sex hormones) or estrogens (female sex hormones). These hormones ...Treatment · Stage I Testicular Cancer · Stage Ii Testicular Cancer<|separator|>
[102]
Gynecomastia Treatment & Management - Medscape Reference
Aug 1, 2024 · A Chinese study indicated that endoscopic subcutaneous mastectomy, without skin excision, could be an effective treatment for gynecomastia. In a ...
[103]
Global research landscape of robotic surgery in gynecologic oncology
Sep 28, 2025 · The 2024 output doubled the 2018 volume, signaling that robot-assisted surgery for gynecological cancers has reached an advanced developmental ...
[104]
Robotic-Assisted Fertility-Sparing Surgery for Early Ovarian Cancer
The estimated survival was 98% at 5 years and 93% at 10 years. Twenty-four patients attempted to become pregnant, and 17 (71%) conceived. These 17 patients had ...
[105]
Perioperative hormone level changes and their clinical implications ...
Oct 29, 2023 · This study employs case data analysis to elucidate alterations in hormone levels pre and post-surgery among patients with pituitary adenoma.
[106]
Ovarian thecoma | Radiology Reference Article | Radiopaedia.org
Oct 8, 2025 · Secondary features of hyperestrogenism, such as endometrial thickening, also may be seen. CT. Typically appear as unilateral, solid ovarian ...
[107]
Ovarian Thecoma Fibroma Causing Menstrual Disorder & Infertility
Ovarian thecoma-fibroma, though uncommon in young premenopausal women, is an important cause of oligomenorrhea, secondary amenorrhea and or infertility. ...Missing: prognosis | Show results with:prognosis
[108]
A case of gigantic ovarian thecoma with normal estrogen during ...
Jul 3, 2025 · An accurate diagnosis is essential before surgery to limit the extent of the surgical procedure and preserve the patient's fertility.
[109]
Granulosa-Theca Cell Tumors - Medscape Reference
Nov 14, 2024 · Granulosa-theca cell tumors, also known as granulosa cell tumors (GCTs), represent about 2% of all ovarian tumors.Practice Essentials · Background · Pathophysiology · Epidemiology
[110]
Recurrent Granulosa Cell Tumor in a Postmenopausal Woman - NIH
Aug 12, 2023 · GCTs are infamous for their tendency to relapse decades after the initial presentation; 15-20% of Stage I tumors will eventually return, usually ...
[111]
Gynecomastia: A systematic review of pharmacological treatments
Nov 1, 2022 · Aromatase inhibitors. Size reduction in patients treated with anastrozole occurred in 36.1%–72.2% (27–29) of patients, with a good response ...
[112]
Gynecomastia | AAFP
Apr 1, 2012 · Attempts to prevent gynecomastia with the use of concomitant tamoxifen or other aromatase inhibitors may result in irreversible adverse effects.Abstract · Physiologic Gynecomastia · Nonphysiologic Gynecomastia · DiagnosisMissing: rate | Show results with:rate<|control11|><|separator|>
[113]
Olaparib maintenance therapy for recurrent adult granulosa cell ...
Sep 19, 2025 · Most AGCTs are limited to the ovary at the time of diagnosis, with a relatively favorable prognosis; however, AGCTs recur in 20%–25% of patients ...
[114]
Adult ovarian granulosa cell tumors: analysis of outcomes and risk ...
The estimated 5-year overall survival was 95.7% and the 5-year progression-free survival was 86.1%. Following univariate Cox regression modeling, only early ...
[115]
Hormone Replacement Therapy and Breast Cancer, Endometrial ...
The study found that women who had used unopposed oestrogen had a relative risk of endometrial cancer of 4.0 (95% confidence interval 3.1-5.1) compared with non ...
[116]
Estrogen and Thrombosis: a Bench to Bedside Review - PMC
Estrogen has also been associated with increased risk of “unusual site” thromboses, as well as arterial thrombosis. Women at high-risk of thrombosis need ...
[117]
Osteoporosis and bone metabolism in patients with Klinefelter ...
Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6–15% of osteoporosis and of 25–48% of osteopenia.Missing: hyperestrogenism | Show results with:hyperestrogenism
[118]
Aromatase inhibitor-associated bone and musculoskeletal effects
This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias.
[119]
Oophorectomy (ovary removal surgery) - Mayo Clinic
Apr 17, 2024 · Oophorectomy may be used in people who have a high risk of ovarian cancer or breast cancer. Oophorectomy lowers the risk of both kinds of cancer ...
[120]
Increased estrogen level can be associated with depression in males
Increased estrogen level was associated with depressive symptomatology regardless of BMI in younger men. Abstract. Background. Several studies have shown a ...Missing: syndrome | Show results with:syndrome<|control11|><|separator|>
[121]
Chapter 24: Estrogens and Body Weight Regulation in Men - PMC
Recent data from clinical intervention studies indicate that estradiol may be a stronger determinant of adiposity than testosterone in men.
[122]
[PDF] Hypothyroidism Web Brochure - American Thyroid Association
For example, if you start taking estrogen in a birth control pill or in hormone ... secondary hypothyroidism: hypothyroidism caused not by damage to the thyroid ...<|control11|><|separator|>