111-592: Leuprorelin , also known as leuprolide , is a manufactured version of a hormone used to treat prostate cancer , breast cancer , endometriosis , uterine fibroids , for early puberty , or as part of transgender hormone therapy . It is given by injection into a muscle or under the skin . Leuprorelin is in the gonadotropin-releasing hormone (GnRH) analogue family of medications. It works by decreasing gonadotropins and therefore decreasing testosterone and estradiol . Common side effects include hot flashes , unstable mood, trouble sleeping , headaches , and pain at
222-593: A depot injection formulation was introduced in 1989. On 24 March 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Camcevi, intended for the treatment of the cancer of the prostate in adult men when the cancer is "hormone-dependent", which means that it responds to treatments that reduce
333-586: A prolactinoma ), or lung cancer , can produce hormones that alter the male–female hormone balance and cause gynecomastia. Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia. The causes of common gynecomastia remain uncertain, but are thought to result from an imbalance between the actions of estrogen, which stimulates breast tissue growth, and androgens, which inhibit breast tissue growth. Breast prominence can result from enlargement of glandular breast tissue, chest adipose tissue (fat) and skin, and
444-428: A 24–65% prevalence of senile gynecomastia in older males. About 10–25% of gynecomastia cases are estimated to result from the use of medications or exogenous chemicals. Drugs can increase estrogen activity or increase the estrogen to androgen ratio through various mechanisms, such as binding to estrogen receptors, promoting estrogen synthesis, providing precursors that can be aromatized into estrogen, causing damage to
555-431: A cascade of secondary effects within the cytoplasm of the cell, described as signal transduction , often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g., cyclic AMP ). Some protein hormones also interact with intracellular receptors located in
666-450: A clinician for potential causes. Dimpling of the skin, nipple discharge, and nipple retraction are not typical features of gynecomastia and may be associated with other disorders . Milky discharge from the nipple is not a typical finding, but may be seen in a gynecomastic individual with a prolactin secreting tumor . An increase in the diameter of the areola and asymmetry of the chest are other possible signs of gynecomastia. Much of
777-576: A competing ligand is bound to the receptor site, the hormone is unable to bind to that site and is unable to elicit a response from the target cell. These competing ligands are called antagonists of the hormone. Many hormones and their structural and functional analogs are used as medication . The most commonly prescribed hormones are estrogens and progestogens (as methods of hormonal contraception and as HRT ), thyroxine (as levothyroxine , for hypothyroidism ) and steroids (for autoimmune diseases and several respiratory disorders ). Insulin
888-476: A diverse range of systemic physiological effects. Different tissue types may also respond differently to the same hormonal signal. Arnold Adolph Berthold was a German physiologist and zoologist , who, in 1849, had a question about the function of the testes . He noticed in castrated roosters that they did not have the same sexual behaviors as roosters with their testes intact. He decided to run an experiment on male roosters to examine this phenomenon. He kept
999-404: A dramatic reduction in estradiol and testosterone levels regardless of sex. Leuprorelin is available in the following forms, among others: The peptide sequence is Pyr-His-Trp-Ser-Tyr- D -Leu-Leu-Arg-Pro-NHEt (Pyr = L - pyroglutamyl ). Leuprorelin was discovered and first patented in 1973 and was introduced for medical use in 1985. It was initially marketed only for daily injection, but
1110-433: A group of roosters with their testes intact, and saw that they had normal sized wattles and combs (secondary sexual organs ), a normal crow, and normal sexual and aggressive behaviors. He also had a group with their testes surgically removed, and noticed that their secondary sexual organs were decreased in size, had a weak crow, did not have sexual attraction towards females, and were not aggressive. He realized that this organ
1221-498: A gynecomastic appearance. Klinefelter syndrome is a notable example of a disorder that causes hypogonadism and gynecomastia, and has a higher risk of breast cancer in males (20–50 times higher than males without the disorder). Secondary hypogonadism (indicating a problem with the brain) leads to decreased production and release of luteinizing hormone (LH, a stimulatory signal for endogenous steroid hormone synthesis) which leads to decreased production of testosterone and estradiol in
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#17327877460131332-580: A hormonal imbalance due to the suppression of testosterone production and testicular damage from high levels of urea also known as uremia-associated hypogonadism. Additionally, gynecomastia has been observed in 50% of patients with chronic kidney disease undergoing dialysis. Similar to the mechanism behind refeeding gynecomastia, dialysis allows patients with renal failure who were previously malnourished to expand their diets and regain weight. Dialysis-associated gynecomastia resolves spontaneously within 1–2 years. In individuals with liver failure or cirrhosis,
1443-587: A hormone-secreting testicular tumor. Markers of testicular, adrenal, or other tumors such as urinary 17-ketosteroid or serum dehydroepiandrosterone may also be checked if there is evidence of hormonal imbalance on physical examination. If this evaluation does not reveal the cause of gynecomastia, then it is considered to be idiopathic gynecomastia (of unclear cause). While there can be many potential causes of male patients that present with increased breast tissue, differential diagnoses are most concerning for gynecomastia, pseudogynecomastia, and breast cancer (which
1554-400: A major site of aromatase activity, leads to increased conversion of androgenic hormones such as testosterone to estrogens. Additionally, levels of sex hormone binding globulin (SHBG) increase with age and bind with less affinity to estrogen than androgens. Put together, the elevated ratio of estrogen to androgen leads to gynecomastia, also known as senile gynecomastia in this group. There is
1665-472: A natural decline in testosterone production. This may occur even if the levels of estrogens and androgens are both appropriate, but the ratio is altered. Gynecomastia is the most common benign disorder of the male breast tissue and affects 35% of men, being most prevalent between the ages of 50 and 69. It is normal for up to 70% of adolescent boys to develop gynecomastia to some degree. Of these, 75% resolve within two years of onset without treatment. If
1776-403: A rapid degradation cycle, making sure they do not reach distant sites within the body. Hormones are also regulated by receptor agonists. Hormones are ligands, which are any kinds of molecules that produce a signal by binding to a receptor site on a protein. Hormone effects can be inhibited, thus regulated, by competing ligands that bind to the same target receptor as the hormone in question. When
1887-431: A rooster with one testis removed, and saw that they had normal behavior and physical anatomy as well. Berthold determined that the location or genetic factors of the testes do not matter in relation to sexual organs and behaviors, but that some chemical in the testes being secreted is causing this phenomenon. It was later identified that this factor was the hormone testosterone . Although known primarily for his work on
1998-410: A testicular tumor should be checked including total and free levels of testosterone , luteinizing hormone , follicle stimulating hormone , estradiol , serum beta human chorionic gonadotropin (β-hCG), and prolactin . High levels of prolactin are uncommon in people with gynecomastia. If β-hCG levels are abnormally high, then ultrasound of the testicles should be performed to check for signs of
2109-429: A type of hormone that share a commonality with neurotransmitters. They are produced by endocrine cells that receive input from neurons, or neuroendocrine cells. Both classic hormones and neurohormones are secreted by endocrine tissue; however, neurohormones are the result of a combination between endocrine reflexes and neural reflexes, creating a neuroendocrine pathway. While endocrine pathways produce chemical signals in
2220-605: A variety of presentations. Minimal androgen insensitivity syndrome may present as gynecomastia in adolescence and may additionally be associated with infertility . Medications are known to cause gynecomastia through several different mechanisms. These mechanisms include increasing estrogen levels, mimicking estrogen, decreasing levels of testosterone or other androgens, blocking androgen receptors, increasing prolactin levels, or through unidentified means. Potential causative agents include oral contraceptive pills , spironolactone , and anabolic steroids . High levels of prolactin in
2331-482: A wide range of processes including both physiological processes and behavioral activities such as digestion , metabolism , respiration , sensory perception , sleep , excretion , lactation , stress induction, growth and development , movement , reproduction , and mood manipulation. In plants, hormones modulate almost all aspects of development, from germination to senescence . Hormones affect distant cells by binding to specific receptor proteins in
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#17327877460132442-456: Is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior . Hormones are required for the correct development of animals , plants and fungi . Due to the broad definition of a hormone (as a signaling molecule that exerts its effects far from its site of production), numerous kinds of molecules can be classified as hormones. Among
2553-456: Is a rare cause of testicular tumors that affect aromatase expression, which results in elevated serum estrogen levels. Aromatase excess syndrome is a rare genetic disorder that leads to increased conversion of androgens to estrogens in the body. Primary hypogonadism (indicating an intrinsic problem with the testes in males) leads to decreased testosterone synthesis and increased conversion of testosterone to estradiol potentially leading to
2664-886: Is associated with gynecomastia in about 80% of cases. Secondary hypogonadism results when there is damage to the hypothalamus or pituitary (due to radiation, chemotherapy, infection, trauma, etc), and similarly lead to impaired androgen production. The net effect is reduced androgen production while serum estrogen levels (from peripheral aromatization of androgens) remain unaffected. The lack of androgen-mediated inhibition of breast tissue proliferation combined with relative estrogen excess result in gynecomastia. Testicular tumors such as Leydig cell tumors , Sertoli cell tumors (such as in Peutz–Jeghers syndrome ) and hCG -secreting choriocarcinoma may result in rapid-onset gynecomastia by causing excess production of estrogen. Other tumors such as adrenal tumors , pituitary gland tumors (such as
2775-400: Is completed (penile and testicular development should reach Tanner scale Stage V). Surgical approaches to the treatment of gynecomastia include subcutaneous mastectomy , liposuction -assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma , surgical wound infection, breast asymmetry, changes in sensation in
2886-405: Is defined as an excess of skin and/or adipose tissue in the male breasts without the growth of true glandular breast tissue ; this is commonly associated with obesity and can be ruled out by physical exam. In gynecomastia there is always enlargement of one or both breasts, symmetrically or asymmetrically, in a man. A soft, compressible, and mobile mass of breast tissue is felt under
2997-541: Is estimated to be present in 24–65 percent of men between the ages of 50 and 80. Estimates on asymptomatic gynecomastia is about up to 70% in men aged 50 to 69 years. The prevalence of gynecomastia in men may have increased in recent years, but the epidemiology of the disorder is not fully understood. The use of anabolic steroids and exposure to chemicals that mimic estrogen in cosmetic products, organochlorine pesticides , and industrial chemicals have been suggested as possible factors driving this increase. According to
3108-484: Is in phase II clinical trials for endometriosis. Leuprorelin is frequently used in ferrets for the treatment of adrenal disease . Its use has been reported in a ferret with concurrent primary hyperaldosteronism , and one with concurrent diabetes mellitus. It is also used to treat pet parrots with chronic egg laying behavior. Hormone A hormone (from the Greek participle ὁρμῶν , "setting in motion")
3219-562: Is in the thyroxine-binding protein which carries up to 80% of all thyroxine in the body, a crucial element in regulating the metabolic rate. Gynecomastia Gynecomastia (also spelled gynaecomastia ) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens . Gynecomastia can cause significant psychological distress or dysphoria . Gynecomastia can be normal in newborn male babies due to exposure to estrogen from
3330-430: Is its USAN Tooltip United States Adopted Name and USP Tooltip United States Pharmacopeia , leuprorelina is its DCIT Tooltip Denominazione Comune Italiana , and leuproréline is its DCF Tooltip Dénomination Commune Française . It is also known by its developmental code names A-43818, Abbott-43818, DC-2-269, and TAP-144. Leuprorelin is marketed by Bayer AG under the brand name Viadur, by Tolmar under
3441-415: Is necessary. The options are medication or surgical intervention. Gynecomastia can respond well to medical treatment although it is usually only effective when done within the first two years after the start of male breast enlargement. Selective estrogen receptor modulators (SERMs) such as tamoxifen , raloxifene , and clomifene may be beneficial in the treatment of gynecomastia but are not approved by
Leuprorelin - Misplaced Pages Continue
3552-531: Is no agreement that these molecules can be called hormones. Peptides Derivatives Compared with vertebrates, insects and crustaceans possess a number of structurally unusual hormones such as the juvenile hormone , a sesquiterpenoid . Examples include abscisic acid , auxin , cytokinin , ethylene , and gibberellin . Most hormones initiate a cellular response by initially binding to either cell surface receptors or intracellular receptors . A cell may have several different receptors that recognize
3663-483: Is not typically necessary. If a tumor of the adrenal glands or the testes is thought to be responsible for the gynecomastia, ultrasound examination of these structures may be performed. Early histological features expected to be seen on examination of gynecomastic tissue attained by fine-needle aspiration biopsy include the following: proliferation and lengthening of the ducts, an increase in connective tissue, an increase in inflammation, and swelling surrounding
3774-405: Is rare in men). Other potential causes of male breast enlargement such as mastitis , lipoma , sebaceous cyst , dermoid cyst , hematoma , metastasis , ductal ectasia , fat necrosis , or a hamartoma are typically excluded before making the diagnosis. Mammography is the method of choice for radiologic examination of male breast tissue in the diagnosis of gynecomastia when breast cancer
3885-548: Is reversible when adequate nutrition resumes, where the return of gonadotropin secretion and gonadal function cause a transient imbalance of estrogen and androgen that mimics puberty, resulting in transient gynecomastia. This phenomenon, also known as refeeding gynecomastia, was first observed when men returning home from prison camps during World War II developed gynecomastia after resuming a normal diet. Similar to pubertal gynecomastia, refeeding gynecomastia resolves on its own in 1–2 years. Many kidney failure patients experience
3996-459: Is self-limited in 75–90% of adolescents and usually resolves spontaneously within 1 to 3 years as pubertal progression increases testosterone levels and cause regression of breast tissue. By age 17, only 10% of adolescent males have persistent gynecomastia. Declining testosterone levels and an increase in the level of subcutaneous fatty tissue seen as part of the normal aging process can lead to gynecomastia in older males. Increased fatty tissue,
4107-412: Is suspected on physical examination. If a mass/lump is felt during a physical exam some features of the lump that would point to malignancy would be painless, non moveable (fixed), irregularly shaped, and skin changes. Mammography is rarely indicated for men since breast cancer is an unlikely diagnosis. If mammography is performed and does not reveal findings suggestive of breast cancer, further imaging
4218-479: Is the ability of pharmacologic doses of glucocorticoids to suppress inflammation . At the neurological level, behavior can be inferred based on hormone concentration, which in turn are influenced by hormone-release patterns; the numbers and locations of hormone receptors; and the efficiency of hormone receptors for those involved in gene transcription. Hormone concentration does not incite behavior, as that would undermine other external stimuli; however, it influences
4329-530: Is the most common benign disorder of the male breast tissue and affects 35 percent of men, being most prevalent between the ages of 50 and 69. New cases of gynecomastia are common in three age populations: newborns, adolescents, and men older than 50 years. Newborn gynecomastia occurs in about 60–90 percent of male babies and most cases resolve on their own in about 2–3 weeks after delivery. During adolescence, on average 33 percent of males are estimated to exhibit signs of gynecomastia. Gynecomastia in older men
4440-434: Is the overproduction of estrogens. A possible cause may be a neoplasm that originates from estrogen-secreting cells. Tumors that produce hCG stimulate production of estradiol while reducing other testicular hormone production. Obesity is another common cause of excess serum estrogens due to the presence of aromatase in peripheral tissue, which is a protein that converts androgens into estrogens. Peutz-Jeghers syndrome
4551-401: Is typically a combination. As in females, estrogen stimulates the growth of breast tissue in males. In addition to directly stimulating breast tissue growth, estrogens indirectly decrease secretion of testosterone by suppressing luteinizing hormone secretion, resulting in decreased testicular secretion of testosterone. One of the main mechanisms for imbalance between estrogens and androgens
Leuprorelin - Misplaced Pages Continue
4662-484: Is unknown in around 25% of cases. Known causes can be physiologic (occurring normally) or non-physiologic due to underlying pathologies such as drug use, chronic disease, tumors, or malnutrition. Physiologic or normal gynecomastia can occur at three timepoints in life: shortly after birth in both female and male infants, during puberty in adolescent males, and in older adults over the age of 60. 60-90% of male and female newborns may show breast development at birth or in
4773-609: Is used by many diabetics . Local preparations for use in otolaryngology often contain pharmacologic equivalents of adrenaline , while steroid and vitamin D creams are used extensively in dermatological practice. A "pharmacologic dose" or "supraphysiological dose" of a hormone is a medical usage referring to an amount of a hormone far greater than naturally occurs in a healthy body. The effects of pharmacologic doses of hormones may be different from responses to naturally occurring amounts and may be therapeutically useful, though not without potentially adverse side effects. An example
4884-725: Is used for suppressing estrogen production in transgender men . It is considered a possible treatment for paraphilias . Leuprorelin has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia. Common side effects of leuprorelin injection include redness/burning/stinging/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, nausea, diarrhea, impotence, testicular shrinkage, constipation, stomach pain, breast swelling or tenderness, acne, joint/muscle aches or pain, trouble sleeping (insomnia), reduced sexual interest, vaginal discomfort/dryness/itching/discharge, vaginal bleeding, swelling of
4995-407: Is usually required. The American Board of Cosmetic Surgery reports surgery is the "most effective known treatment for gynecomastia." Surgical treatment should be considered if the gynecomastia persists for more than 12 months, causes distress (ie physical discomfort or psychological distress), and is in the fibrotic stage. In adolescent males, it is recommended that surgery is postponed until puberty
5106-528: The American Society of Plastic Surgeons , breast reduction surgeries to correct gynecomastia are fairly common but has been a recent decline. In 2020, there were over 18,000 procedures of this type performed in the United States which is down 11% compared to in 2019. The term gynaecomastia was coined by Galen . He also recognised glandular enlargement of the male breast; however, this wasn't
5217-497: The False Claims Act with claims filed by Douglas Durand, a former TAP vice president of sales, and Joseph Gerstein, a doctor at Tufts University 's HMO practice. Durand, Gerstein, and Tufts shared $ 95 million of the settlement. There have since been various suits concerning leuprorelin use, none successful. They either concern the oversubscription of the drug or undue warning about the side effects. Between 2010 and 2013,
5328-683: The Food and Drug Administration for use in gynecomastia. Clomifene seems to be less effective than tamoxifen or raloxifene. Tamoxifen may be used to treat gynecomastia in adults and of the medical treatments used, tamoxifen is the most effective. Recent studies have shown that treatment with tamoxifen may represent a safe and effective mode of treatment in cases of cosmetically disturbing or painful gynecomastia. Aromatase inhibitors (AIs) such as anastrozole have been used off-label for cases of gynecomastia occurring during puberty but are less effective than SERMs. A few cases of gynecomastia caused by
5439-453: The Theory of Evolution , Charles Darwin was also keenly interested in plants. Through the 1870s, he and his son Francis studied the movement of plants towards light. They were able to show that light is perceived at the tip of a young stem (the coleoptile ), whereas the bending occurs lower down the stem. They proposed that a 'transmissible substance' communicated the direction of light from
5550-418: The bloodstream , typically via fenestrated capillaries , whereas the exocrine system secretes its hormones indirectly using ducts . Hormones with paracrine function diffuse through the interstitial spaces to nearby target tissue. Plants lack specialized organs for the secretion of hormones, although there is spatial distribution of hormone production. For example, the hormone auxin is produced mainly at
5661-472: The cytoplasm or nucleus by an intracrine mechanism. For steroid or thyroid hormones, their receptors are located inside the cell within the cytoplasm of the target cell. These receptors belong to the nuclear receptor family of ligand-activated transcription factors . To bind their receptors, these hormones must first cross the cell membrane. They can do so because they are lipid-soluble. The combined hormone-receptor complex then moves across
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#17327877460135772-450: The hypothalamic–pituitary–gonadal axis (HPG axis). However, normal functioning of this axis requires pulsatile release of GnRH from the hypothalamus. Continuous exposure to an agonist such as leuprorelin for several weeks causes pituitary GnRH receptors to become desensitised and no longer responsive. This desensitisation is the objective of leuprorelin therapy because it ultimately reduces LH and FSH secretion, leading to hypogonadism and
5883-438: The nipple and its surrounding skin in contrast to softer fatty tissue which is not associated with a mass. It may also be accompanied by breast tenderness or nipple sensitivity, which is commonly associated with gynecomastia observed in adolescents, typically early in development. Gynecomastia that is painful, bothersome, rapidly-growing, associated with masses in other areas of the body, or persistent should be evaluated by
5994-542: The thyroid , which increases output of thyroid hormones . To release active hormones quickly into the circulation , hormone biosynthetic cells may produce and store biologically inactive hormones in the form of pre- or prohormones . These can then be quickly converted into their active hormone form in response to a particular stimulus. Eicosanoids are considered to act as local hormones. They are considered to be "local" because they possess specific effects on target cells close to their site of formation. They also have
6105-459: The FDA has not established that these conditions were caused by leuprorelin. During the initial phase of luteinizing hormone-releasing hormone (LHRH) agonist therapy in individuals assigned male at birth , there is a notable phenomenon known as the "flare." This occurs when testosterone levels temporarily surge by approximately 50% within the first 1 to 2 weeks of therapy. This increase is a response to
6216-470: The FDA updated the Lupron drug label to include new safety information on the risk of thromboembolism, loss of bone density and convulsions. The FDA then asserted that the benefits of leuprorelin outweigh its risks when used according to its approved labeling. Since 2017, the FDA has been evaluating leuprorelin's connection to pain and discomfort in musculoskeletal and connective tissue. As of 2006, leuprorelin
6327-471: The Lupron label advises against using the drug when one is considering pregnancy, due to a risk of birth defects. It may be used to reduce the risk of premature ovarian failure in women receiving cyclophosphamide for chemotherapy. Along with triptorelin and goserelin , it has been used to delay puberty in transgender youth until they are old enough to begin hormone replacement therapy . Researchers have recommended puberty blockers after age 12, when
6438-404: The amount and distribution of pubic and underarm hair . Gynecomastia usually presents with bilateral involvement of the breast tissue but may occur unilaterally as well. Diagnosis of men with breast enlargement can be evaluated using an algorithm . A review of the medications or substances an individual takes may reveal the cause of gynecomastia. Recommended laboratory investigations to find
6549-530: The ankles/feet, increased urination at night, dizziness, breakthrough bleeding in a female child during the first two months of leuprorelin treatment, weakness, chills, clammy skin, skin redness, itching, or scaling, testicle pain, impotence, depression, or memory problems. The rates of gynecomastia with leuprorelin have been found to range from 3 to 16%. A cohort of women that were prescribed leuprorelin to delay precocious puberty as children has developed osteoporosis and brittle teeth at an unexpected rate; However,
6660-491: The basis that it is a cosmetic procedure. Gynecomastia itself is a benign finding. It does not confer a poor prognosis, for some patients with underlying pathologies such as testicular cancer the prognosis may be worse. The glandular tissue typically grows under the influence of hormonal stimulation and is often tender or painful. Furthermore, gynecomastia frequently presents social and psychological difficulties such as low self-esteem, depression or shame. Gynecomastia
6771-402: The behaviors affected by episodically secreted hormones directly prevent the continuous release of sad hormones. Three broad stages of reasoning may be used to determine if a specific hormone-behavior interaction is present within a system: Though colloquially oftentimes used interchangeably, there are various clear distinctions between hormones and neurotransmitters : Neurohormones are
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#17327877460136882-520: The blood (which may occur as a result of certain tumors or as a side effect of certain medications) has been associated with gynecomastia. A high level of prolactin in the blood can inhibit the release of gonadotropin-releasing hormone and therefore cause secondary hypogonadism. Receptors for prolactin and other hormones including insulin-like growth factor 1 , insulin-like growth factor 2 , luteinizing hormone , progesterone , and human chorionic gonadotropin have been found in male breast tissue, but
6993-563: The brand names Eligard and Fensolvi, and by TAP Pharmaceuticals (1985–2008), by Varian Pharmed( Previously named Varian Darou Pajooh) under the brand name Leupromer and Abbott Laboratories (2008–present) under the brand name Lupron. In October 2001, the US Department of Justice, states attorneys general, and TAP Pharmaceutical Products, a subsidiary of Abbott Laboratories, settled criminal and civil charges against TAP related to federal and state medicare fraud and illegal marketing of
7104-447: The breast, necrosis of the areola or nipple, seroma , noticeable or painful scars, and contour deformities. In 2019, 24,123 male patients underwent surgical treatment for gynecomastia in the United States, accounting for a 19% increase since 2000. Thirty-five percent of those patients were between the ages of 20 and 29, and 60% were younger than age 29 at the time of the operation. At an average surgeon's fee of $ 4,123, gynecomastia surgery
7215-536: The cell surface. In vertebrates, endocrine glands are specialized organs that secrete hormones into the endocrine signaling system . Hormone secretion occurs in response to specific biochemical signals and is often subject to negative feedback regulation . For instance, high blood sugar (serum glucose concentration) promotes insulin synthesis. Insulin then acts to reduce glucose levels and maintain homeostasis , leading to reduced insulin levels. Upon secretion, water-soluble hormones are readily transported through
7326-474: The circulatory system. Lipid-soluble hormones must bond to carrier plasma glycoproteins (e.g., thyroxine-binding globulin (TBG)) to form ligand -protein complexes. Some hormones, such as insulin and growth hormones, can be released into the bloodstream already fully active. Other hormones, called prohormones , must be activated in certain cells through a series of steps that are usually tightly controlled. The endocrine system secretes hormones directly into
7437-545: The condition does not resolve within 2 years, or if it causes embarrassment, pain or tenderness, treatment is warranted. Medical treatment of gynecomastia that has persisted beyond two years is often ineffective. Gynecomastia is different from " pseudogynecomastia ", which is commonly present in men with obesity . Medications such as aromatase inhibitors have been found to be effective and even in rare cases of gynecomastia from disorders such as aromatase excess syndrome or Peutz–Jeghers syndrome , but surgical removal of
7548-509: The drug leuprorelin. TAP paid a total of $ 875 million, which was a record high at the time . The $ 875 million settlement broke down to $ 290 million for violating the Prescription Drug Marketing Act, $ 559.5 million to settle federal fraud charges for overcharging Medicare, and $ 25.5 million reimbursement to 50 states and Washington, D.C., for filing false claims with the states' Medicaid programs. The case arose under
7659-413: The ducts, and an increase in fibroblasts in the connective tissue. Chronic gynecomastia may show different histological features such as increased connective tissue fibrosis , an increase in the number of ducts, less inflammation than in the acute stage of gynecomastia, increased subareolar fat, and hyalinization of the stroma. When surgery is performed, the gland is routinely sent to the lab to confirm
7770-537: The effects of testosterone from acting on its target tissues. Androgen insensitivity syndromes result from the different degrees of resistance to the effects of androgens, and can cause external genitalia that may not be aligned with the genotype of the individual's sex chromosomes . Complete androgen insensitivity syndrome results in the failure to develop external genitalia such as the penis and scrotum along with development of breasts in an individual with testes. Partial androgen insensitivity syndrome may result in
7881-502: The excess tissue can be needed to correct the condition. In 2019, 24,123 male patients underwent the procedure in the United States , accounting for a 19% increase since 2000. Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogen and androgen . Gynecomastia is different from " pseudogynecomastia ", which
7992-450: The first weeks of life. During pregnancy, the placenta converts the androgenic hormones dehydroepiandrosterone (DHEA) and DHEA sulfate to the estrogenic hormones estrone and estradiol , respectively; after these estrogens are produced by the placenta, they are transferred into the baby's circulation, thereby leading to temporary gynecomastia in the baby. In some infants, neonatal milk (also known as " witch's milk ") can leak from
8103-412: The following steps: Exocytosis and other methods of membrane transport are used to secrete hormones when the endocrine glands are signaled. The hierarchical model is an oversimplification of the hormonal signaling process. Cellular recipients of a particular hormonal signal may be one of several cell types that reside within a number of different tissues, as is the case for insulin , which triggers
8214-432: The form of hormones, the neuroendocrine pathway involves the electrical signals of neurons. In this pathway, the result of the electrical signal produced by a neuron is the release of a chemical, which is the neurohormone . Finally, like a classic hormone, the neurohormone is released into the bloodstream to reach its target. Hormone transport and the involvement of binding proteins is an essential aspect when considering
8325-400: The function of hormones. The formation of a complex with a binding protein has several benefits: the effective half-life of the bound hormone is increased, and a reservoir of bound hormones is created, which evens the variations in concentration of unbound hormones (bound hormones will replace the unbound hormones when these are eliminated). An example of the usage of hormone-binding proteins
8436-764: The impact of these various hormones on gynecomastia development is not well understood. Individuals who have cirrhosis or chronic liver disease may develop gynecomastia for several reasons. Those diagnosed with cirrhosis tend to have increased secretion of the androgenic hormone androstenedione from the adrenal glands, increased conversion of this hormone into various types of estrogen, and increased levels of SHBG, which leads to decreased blood levels of free testosterone. Around 10–40% of males with Graves' disease (a common form of hyperthyroidism ) experience gynecomastia. Increased conversion of testosterone to estrogen by increased aromatase activity, increased levels of SHBG and increased production of testosterone and estradiol by
8547-521: The initial stimulation of luteinizing hormone (LH) by the LHRH agonist, leading to a rise in testosterone levels before they begin to decrease as intended. For individuals receiving LHRH agonists as part of gender-affirming care, this temporary increase in testosterone can be particularly distressing, exacerbating gender dysphoria and discomfort. To manage and mitigate these effects, healthcare providers often prescribe antiandrogens during this phase to help block
8658-593: The levels of the hormone testosterone. The applicant for this medicinal product is Accord Healthcare S.L.U. Leuprorelin was approved for medical use in the European Union in May 2022. Leuprorelin is the generic name of the drug and its INN Tooltip International Nonproprietary Name and BAN Tooltip British Approved Name , while leuprorelin acetate is its BANM Tooltip British Approved Name and JAN Tooltip Japanese Accepted Name , leuprolide acetate
8769-637: The liver's ability to properly metabolize hormones such as estrogen may be impaired. Additionally, those with alcoholic liver disease are further put at risk for development of gynecomastia; ethanol may directly disrupt the synthesis of testosterone and the presence of phytoestrogens in alcoholic drinks may also contribute to a higher estrogen to testosterone ratio. Conditions that can cause malabsorption such as cystic fibrosis or ulcerative colitis may also produce gynecomastia. A small proportion of male gynecomastia cases may be seen with rare inherited disorders such as spinal and bulbar muscular atrophy and
8880-543: The mother, in adolescent boys going through puberty , in older men over the age of 50, and in obese men. Most occurrences of gynecomastia do not require diagnostic tests. Gynecomastia may be caused by abnormal hormone changes, any condition that leads to an increase in the ratio of estrogens / androgens such as liver disease , kidney failure , thyroid disease and some non-breast tumors . Alcohol and some drugs can also cause breast enlargement. Other causes may include Klinefelter syndrome , metabolic dysfunction , or
8991-413: The negative feedback mechanism. Negative feedback must be triggered by overproduction of an "effect" of the hormone. Hormone secretion can be stimulated and inhibited by: One special group of hormones is the tropic hormones that stimulate the hormone production of other endocrine glands . For example, thyroid-stimulating hormone (TSH) causes growth and increased activity of another endocrine gland,
9102-455: The nipples. The temporary gynecomastia seen in newborn babies usually resolves after two or three weeks. Hormonal imbalance (elevated ratio of estrogen to androgen) during early puberty, either due to decreased androgen production from the adrenals and/or increased conversion of androgens to estrogens, leads to transient gynecomastia in adolescent males. It can occur in up to 65% of adolescents as early as age 10 and peaks at ages 13 and 14. It
9213-433: The nuclear membrane into the nucleus of the cell, where it binds to specific DNA sequences , regulating the expression of certain genes , and thereby increasing the levels of the proteins encoded by these genes. However, it has been shown that not all steroid receptors are located inside the cell. Some are associated with the plasma membrane . Hormones have the following effects on the body: A hormone may also regulate
9324-405: The passage of food from the stomach to the intestines , which they believed to be due to the nervous system. They cut the nerves to the pancreas in an animal model and discovered that it was not nerve impulses that controlled secretion from the pancreas. It was determined that a factor secreted from the intestines into the bloodstream was stimulating the pancreas to secrete digestive fluids. This
9435-443: The person has developed to Tanner stages 2–3, and then cross-sex hormones treatment at age 16. This use of the drug is off-label, however, not having been approved by the Food and Drug Administration and without data on long-term effects of this use. They are also sometimes used as alternatives to antiandrogens like spironolactone and cyproterone acetate for suppressing testosterone production in transgender women . It also
9546-562: The possibility of having breast cancer . Particular studies suggest that gynecomastia can lead to various psychological and social challenges, such as depression, anxiety and disordered eating. Gynecomastia is thought to be caused by an altered ratio of estrogens to androgens mediated by an increase in estrogen action, a decrease in androgen action, or a combination of these two factors. Estrogen and androgens have opposing actions on breast tissue: estrogens stimulate proliferation while androgens inhibit proliferation. The cause of gynecomastia
9657-434: The presence of gynecomastia and to check for tumors under a microscope. The utility of pathologic examination of breast tissue removed from male adolescent gynecomastia patients has recently been questioned due to the rarity of breast cancer in this population. The spectrum of gynecomastia severity has been categorized into a grading system: If the gynecomastia doesn't resolve on its own in two years, then medical treatment
9768-408: The production and release of other hormones. Hormone signals control the internal environment of the body through homeostasis . The rate of hormone biosynthesis and secretion is often regulated by a homeostatic negative feedback control mechanism. Such a mechanism depends on factors that influence the metabolism and excretion of hormones. Thus, higher hormone concentration alone cannot trigger
9879-517: The rare disorders aromatase excess syndrome and Peutz–Jeghers syndrome have responded to treatment with AIs such as anastrozole. Androgens / anabolic steroids may be effective for gynecomastia. Testosterone itself may not be suitable to treat gynecomastia as it can be aromatized into estradiol, but nonaromatizable androgens like topical androstanolone (dihydrotestosterone) can be useful. If chronic gynecomastia does not respond to medical treatment, surgical removal of glandular breast tissue
9990-548: The research on gynecomastia has focused on its causes and treatment, but little has explored its effects on mental health and overall quality of life. Gynecomastia has psychosocial implications that may be particularly challenging for adolescents who are experiencing physical maturation and self-identity formation, which includes body image disturbances, negative attitudes towards eating, self-esteem problems, social withdrawal, anxiety, and shame. Men with gynecomastia may appear anxious or stressed due to concerns about its appearance and
10101-518: The same hormone but activate different signal transduction pathways, or a cell may have several different receptors that recognize different hormones and activate the same biochemical pathway. Receptors for most peptide as well as many eicosanoid hormones are embedded in the cell membrane as cell surface receptors, and the majority of these belong to the G protein-coupled receptor (GPCR) class of seven alpha helix transmembrane proteins. The interaction of hormone and receptor typically triggers
10212-516: The site of injection. Other side effects may include high blood sugar , allergic reactions , and problems with the pituitary gland . Use during pregnancy may harm foetal development. Leuprorelin was patented in 1973 and approved for medical use in the United States in 1985. It is on the World Health Organization's List of Essential Medicines . It is sold under the brand name Lupron among others. Leuprorelin may be used in
10323-399: The substance causing the physiological changes, was the first hormone to be discovered. The term hormone would later be coined by Starling. William Bayliss and Ernest Starling , a physiologist and biologist , respectively, wanted to see if the nervous system had an impact on the digestive system . They knew that the pancreas was involved in the secretion of digestive fluids after
10434-457: The substances that can be considered hormones, are eicosanoids (e.g. prostaglandins and thromboxanes ), steroids (e.g. oestrogen and brassinosteroid ), amino acid derivatives (e.g. epinephrine and auxin ), protein or peptides (e.g. insulin and CLE peptides ), and gases (e.g. ethylene and nitric oxide ). Hormones are used to communicate between organs and tissues . In vertebrates , hormones are responsible for regulating
10545-499: The surface of target cells via second messengers . Lipid soluble hormones, (such as steroids ) generally pass through the plasma membranes of target cells (both cytoplasmic and nuclear ) to act within their nuclei . Brassinosteroids, a type of polyhydroxysteroids, are a sixth class of plant hormones and may be useful as an anticancer drug for endocrine-responsive tumors to cause apoptosis and limit plant growth. Despite being lipid soluble, they nevertheless attach to their receptor at
10656-485: The system by increasing the probability of a certain event to occur. Not only can hormones influence behavior, but also behavior and the environment can influence hormone concentration. Thus, a feedback loop is formed, meaning behavior can affect hormone concentration, which in turn can affect behavior, which in turn can affect hormone concentration, and so on. For example, hormone-behavior feedback loops are essential in providing constancy to episodic hormone secretion, as
10767-417: The target cell, resulting in a change in cell function. When a hormone binds to the receptor, it results in the activation of a signal transduction pathway that typically activates gene transcription , resulting in increased expression of target proteins . Hormones can also act in non-genomic pathways that synergize with genomic effects. Water-soluble hormones (such as peptides and amines) generally act on
10878-711: The testes due to elevated levels of LH cause the gynecomastia. Proper treatment of the hyperthyroidism can lead to the resolution of the gynecomastia. To diagnose gynecomastia, a thorough history and physical examination are obtained by a physician . Important aspects of the physical examination include evaluation of the male breast tissue with palpation to evaluate for breast cancer and pseudogynecomastia (male breast tissue enlargement solely due to excess fatty tissue ), evaluation of penile size and development, evaluation of testicular development and an assessment for masses that raise suspicion for testicular cancer , and proper development of secondary sex characteristics such as
10989-1218: The testes, inhibiting testosterone synthesis, inhibiting the action of androgens, or displacing estrogen from SHBG. Drugs with good evidence for association with gynecomastia include cimetidine , ketoconazole , gonadotropin-releasing hormone analogues , human growth hormone , human chorionic gonadotropin , 5α-reductase inhibitors such as finasteride and dutasteride , certain estrogens used for prostate cancer , and antiandrogens such as bicalutamide , flutamide , and spironolactone . Drugs with fair evidence for association with gynecomastia include calcium channel blockers such as verapamil , amlodipine , and nifedipine ; risperidone , olanzapine , anabolic steroids , alcohol , opioids , efavirenz , alkylating agents , and omeprazole . Certain components of personal skin care products such as lavender or tea tree oil have been reported to cause prepubertal gynecomastia due to its estrogenic and anti-androgenic effects. Certain dietary supplements such as dong quai and Tribulus terrestris have also been associated with gynecomastia. Malnutrition and significant loss of body fat suppress gonadotropin secretion, leading to hypogonadism . This
11100-424: The testes. Estrogens can increase blood levels of the protein sex hormone-binding globulin (SHBG), which binds free testosterone (the active form) more strongly than estrogen, leading to decreased action of testosterone in male breast tissue. Conditions such as hyperthyroidism and chronic liver disease affect levels of SHBG, leading to symptomatic gynecomastia. Dysfunction in the androgen receptor prevents
11211-440: The tip down to the stem. The idea of a 'transmissible substance' was initially dismissed by other plant biologists, but their work later led to the discovery of the first plant hormone. In the 1920s Dutch scientist Frits Warmolt Went and Russian scientist Nikolai Cholodny (working independently of each other) conclusively showed that asymmetric accumulation of a growth hormone was responsible for this bending. In 1933 this hormone
11322-406: The tips of young leaves and in the shoot apical meristem . The lack of specialised glands means that the main site of hormone production can change throughout the life of a plant, and the site of production is dependent on the plant's age and environment. Hormone producing cells are found in the endocrine glands , such as the thyroid gland , ovaries , and testes . Hormonal signaling involves
11433-409: The treatment of hormone-responsive cancers such as prostate cancer and breast cancer . It may also be used for estrogen-dependent conditions such as endometriosis or uterine fibroids . It may be used for precocious puberty in both males and females, and to prevent premature ovulation in cycles of controlled ovarian stimulation for in vitro fertilization ( IVF ). This use is controversial since
11544-439: The underlying cause of gynecomastia include tests for aspartate transaminase and alanine transaminase to rule out liver disease, serum creatinine to determine if kidney damage is present, and thyroid-stimulating hormone levels to evaluate for hyperthyroidism. If these initial laboratory tests fail to uncover the cause of gynecomastia, then additional tests to evaluate for an underlying hormonal balance due to hypogonadism or
11655-419: The unwanted increase in testosterone and alleviate the associated distress. Leuprorelin is a gonadotropin-releasing hormone (GnRH) analogue acting as an agonist at pituitary GnRH receptors . GnRH receptor agonists initially increase the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary and increased serum estradiol and testosterone levels via
11766-471: The very rare aromatase excess syndrome . Gynecomastia can be caused by absolute deficiency in androgen production due to primary or secondary hypogonadism. Primary hypogonadism results when there is damage to the testes (due to radiation, chemotherapy, infections, trauma, etc), leading to impaired androgen production. It can also be caused by chromosomal abnormality seen in Klinefelter syndrome, which
11877-523: Was also the 11th most costly male cosmetic surgery of 2019. Radiation therapy and tamoxifen have been shown to help prevent gynecomastia and breast pain from developing in prostate cancer patients who will be receiving androgen deprivation therapy. The efficacy of these treatments is limited once gynecomastia has occurred and are therefore most effective when used prophylactically. In the United States, many insurance companies deny coverage for surgery for gynecomastia treatment or male breast reduction on
11988-423: Was essential for these behaviors, but he did not know how. To test this further, he removed one testis and placed it in the abdominal cavity. The roosters acted and had normal physical anatomy . He was able to see that location of the testes does not matter. He then wanted to see if it was a genetic factor that was involved in the testes that provided these functions. He transplanted a testis from another rooster to
12099-520: Was finally isolated by Kögl, Haagen-Smit and Erxleben and given the name ' auxin '. British physician George Oliver and physiologist Edward Albert Schäfer , professor at University College London, collaborated on the physiological effects of adrenal extracts. They first published their findings in two reports in 1894, a full publication followed in 1895. Though frequently falsely attributed to secretin , found in 1902 by Bayliss and Starling, Oliver and Schäfer's adrenal extract containing adrenaline ,
12210-601: Was named secretin : a hormone. Hormonal effects are dependent on where they are released, as they can be released in different manners. Not all hormones are released from a cell and into the blood until it binds to a receptor on a target. The major types of hormone signaling are: As hormones are defined functionally, not structurally, they may have diverse chemical structures. Hormones occur in multicellular organisms ( plants , animals , fungi , brown algae , and red algae ). These compounds occur also in unicellular organisms , and may act as signaling molecules however there
12321-442: Was under investigation for possible use in the treatment of mild to moderate Alzheimer's disease . A by mouth formulation of leuprorelin is under development for the treatment of endometriosis . It was also under development for the treatment of precocious puberty , prostate cancer , and uterine fibroids , but development for these uses was discontinued. The formulation has the tentative brand name Ovarest. As of July 2018, it
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