113-479: David Reimer (born Bruce Peter Reimer ; 22 August 1965 – 4 May 2004) was a Canadian man raised as a girl following medical advice and intervention after his penis was severely injured during a botched circumcision in infancy . The psychologist John Money oversaw the case and reported the reassignment as successful and as evidence that gender identity is primarily learned. The academic sexologist Milton Diamond later reported that Reimer's realization that he
226-477: A dorsal slit ), which remains until blood flow has stopped. Finally, the foreskin is amputated . For older babies and adults, circumcision is often performed surgically without specialized instruments, and alternatives such as Unicirc or the Shang ring are available. The circumcision procedure causes pain, and for neonates this pain may interfere with mother-infant interaction or cause other behavioral changes, so
339-520: A psychologist who was developing a reputation as a pioneer in the field of sexual development and gender identity , based on his work with intersex patients. Money was a prominent proponent of the "theory of gender neutrality"—that gender identity developed primarily as a result of social learning from early childhood and that it could be changed with the appropriate behavioural interventions. The Reimers had seen Money being interviewed in February 1967 on
452-517: A 2014 review, the effect of circumcision on sexual partners' experiences is unclear as this has not been well studied. According to a policy statement from the Canadian Paediatric Society that was reaffirmed in 2021, "medical studies do not support circumcision as having an impact on sexual function or satisfaction for partners of circumcised individuals". There are popular misconceptions that circumcision benefits or adversely impacts
565-399: A Girl (2000), in which Colapinto described how—contrary to Money's reports—when living as Brenda, Reimer did not identify as a girl. He was ostracized and bullied by peers (who dubbed him "cavewoman"), and neither frilly dresses nor female hormones made him feel female. In addition to his difficult lifelong relationship with his parents, Reimer was unemployed and experienced remorse due to
678-498: A Girl", discusses the impact on two competing psychological theories of nature vs. nurture. Archival footage of Reimer and his story was included in the 2023 documentary about intersexuality, Every Body . Reimer's story was included in Chapter 11 of American author Sam Kean 's 2021 nonfiction book The Icepick Surgeon , which chronicles many instances of scientific and medical malpractice over time. Circumcision Circumcision
791-555: A contributing cause of the Bar Kokhba revolt . According to Silverman (2006), these restrictions were part of a "broad campaign" by the Romans to "civilize" the Jewish people, viewing the practice as repulsive and analogous to castration . His successor, Antoninus Pius , altered the edict to permit Brit Milah . During this period in history, Jewish circumcision called for the removal of only
904-509: A form of preventive healthcare , as a religious obligation , or as a cultural practice . It is also an option for cases of phimosis , other pathologies that do not resolve with other treatments, and chronic urinary tract infections (UTIs). The procedure is contraindicated in cases of certain genital structure abnormalities or poor general health. The procedure is associated with reduced rates of sexually transmitted infections and urinary tract infections . This includes reducing
1017-577: A male gender identity, calling himself David. He underwent treatment to reverse the reassignment, including testosterone injections, a double mastectomy , and phalloplasty operations. Reimer worked in a slaughterhouse and then worked doing odd jobs. On 22 September 1990, he married Jane Fontane and would adopt her three children. His hobbies included camping, fishing, antiques and collecting old coins. His case came to international attention in 1997 when he told his story to Milton Diamond , an academic sexologist who persuaded Reimer to allow him to report
1130-645: A mark of distinction for the elite: the Egyptian Book of the Dead describes the sun god Ra as having circumcised himself. Circumcision is prominent in the Hebrew Bible . In addition to proposing that circumcision was adopted by the Israelites purely as a religious mandate, scholars have suggested that Judaism's patriarchs and their followers adopted circumcision to make penile hygiene easier in hot, sandy climates; as
1243-720: A molecular level estrogen induces the above-mentioned effects on cell via acting on intracellular receptors termed ER α and ER β, which upon ligation form either homo or heterodimers. The genetic and nongenetic targets of the receptors differ between homo and heterodimers. Ligation of these receptors allows them to translocate to the nucleus and act as transcription factors either by binding estrogen response elements (ERE) on DNA or binding DNA together with other transcriptional factors e.g. Nf-kB or AP-1 , both of which result in RNA polymerase recruitment and further chromatin remodelation . A non-transcriptional response to oestrogen stimulation
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#17328523202911356-408: A part of the prepuce, and Hellenized Jews often attempted to look uncircumcised by stretching the extant parts of their foreskins. This was considered by the Jewish leaders to be a serious problem, and during the second century CE they changed the requirements of Jewish circumcision to call for the complete removal of the foreskin, emphasizing the Jewish view of circumcision as intended to be not just
1469-551: A particularly low prevalence of circumcised males. This region has a disproportionately high HIV infection rate, with a significant number of those infections stemming from heterosexual transmission. As a result, the promotion of prophylactic circumcision has been a priority intervention in that region since the WHO's 2007 recommendations. The International Antiviral Society–USA also suggests circumcision be discussed with men who have insertive anal sex with men , especially in regions where HIV
1582-473: A photograph of the two children doing these activities. When either child resisted these activities, Money would get angry. Both David and Brian recall that Money was mild-mannered around their parents, but ill-tempered when alone with them. When they resisted inspecting each other's genitals, Money got very aggressive. David says, "He told me to take my clothes off, and I just did not do it. I just stood there. And he screamed, 'Now!' Louder than that. I thought he
1695-649: A placebo, but the American Academy of Pediatrics (AAP) states that such methods are insufficient alone and should be used to supplement more effective techniques. A quicker procedure reduces duration of pain; use of the Mogen clamp was found to result in a shorter procedure time and less pain-induced stress than the use of the Gomco clamp or the Plastibell. The available evidence does not indicate that post-procedure pain management
1808-700: A prophylactic or treatment option in healthcare, circumcision plays a major role in many of the world's cultures and religions, most prominently Judaism and Islam . Circumcision is among the most important commandments in Judaism . It is widespread in Australia, Canada, the United States, South Korea, most of Africa, and parts of Asia. It is relatively rare for non-religious reasons in parts of Southern Africa, Latin America, Europe, and parts of Asia. The origin of circumcision
1921-436: A reduced risk of cervical cancer (which is caused by a type of HPV) in female partners of men. There is some evidence that circumcision is associated with reduced risk of prostate cancer . A 2017 systematic review found consistent evidence that male circumcision prior to heterosexual contact was associated with a decreased risk of cervical cancer, cervical dysplasia , HSV-2, chlamydia, and syphilis among women. The evidence
2034-596: A rite of passage into adulthood; or as a form of blood sacrifice. Historical campaigns of ethnic, cultural, and religious persecution frequently included bans on circumcision as a means of forceful assimilation, conversion, and ethnocide . Alexander the Great conquered the Middle East in the fourth century BCE, and in the following centuries ancient Greek cultures and values came to the Middle East. The Greeks abhorred circumcision, making life for circumcised Jews living among
2147-481: A role in suppressing binge eating . Hormone replacement therapy using estrogen may be a possible treatment for binge eating behaviors in females. Estrogen replacement has been shown to suppress binge eating behaviors in female mice. The mechanism by which estrogen replacement inhibits binge-like eating involves the replacement of serotonin (5-HT) neurons. Women exhibiting binge eating behaviors are found to have increased brain uptake of neuron 5-HT, and therefore less of
2260-428: A spiritual concept, arguing literal circumcision to be unnecessary for Gentile converts to Christianity. The teaching that circumcision was unnecessary for membership in a divine covenant was instrumental to the separation of Christianity from Judaism. While the circumcision of Jesus is celebrated as a feast day in the liturgical calendar of many Christian denominations . Although it is not explicitly mentioned in
2373-423: A strong protective effect against penile cancer in later life. Penile cancer is a rare disease in the developed world but much more prevalent in the developing world . The penile tissue removed during circumcision is a potential origin for penile cancer. Risk-benefit considerations around the use of circumcision as a cancer-preventive measure are a source of debate. Penile cancer development can be detected in
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#17328523202912486-405: Is a procedure that removes the foreskin from the human penis . In the most common form of the operation, the foreskin is extended with forceps , then a circumcision device may be placed, after which the foreskin is excised . Topical or locally injected anesthesia is generally used to reduce pain and physiologic stress . Circumcision is generally electively performed , most commonly done as
2599-795: Is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics . There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane , is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy. Estrogens are synthesized in all vertebrates and some insects. Quantitatively, estrogens circulate at lower levels than androgens in both men and women. While estrogen levels are significantly lower in males than in females, estrogens nevertheless have important physiological roles in males. Like all steroid hormones , estrogens readily diffuse across
2712-467: Is a risk that the circumcision scar may be tender. There is no good evidence that circumcision affects cognitive abilities. Circumcision is the oldest known surgical procedure. Depictions of circumcised penises are found in Paleolithic art , predating the earliest signs of trepanation . The history of the migration and evolution of circumcision is known mainly from the cultures of two regions. In
2825-405: Is also used to treat various pathologies. These include pathological phimosis , refractory balanoposthitis and chronic or recurrent urinary tract infections (UTIs). Circumcision is contraindicated in certain cases. These include infants with certain genital structure abnormalities, such as a misplaced urethral opening (as in hypospadias and epispadias ), curvature of the head of
2938-765: Is associated with decreased estradiol and increased progesterone. Klump et al. Progesterone may moderate the effects of low estradiol (such as during dysregulated eating behavior), but that this may only be true in women who have had clinically diagnosed binge episodes (BEs). Dysregulated eating is more strongly associated with such ovarian hormones in women with BEs than in women without BEs. The implantation of 17β-estradiol pellets in ovariectomized mice significantly reduced binge eating behaviors and injections of GLP-1 in ovariectomized mice decreased binge-eating behaviors. The associations between binge eating, menstrual-cycle phase and ovarian hormones correlated. In rodents, estrogens (which are locally aromatized from androgens in
3051-460: Is common. There is evidence that circumcision is associated with a reduced risk of HIV infection for such men, particularly in low-income countries. The finding that circumcision significantly reduces female-to-male HIV transmission has prompted medical organizations serving communities affected by endemic HIV/AIDS to promote circumcision as an additional method of controlling the spread of HIV. Major medical organizations hold varying positions on
3164-459: Is critical in mediating breast development during puberty , as well as breast maturation during pregnancy in preparation of lactation and breastfeeding . Estrogen is primarily and directly responsible for inducing the ductal component of breast development, as well as for causing fat deposition and connective tissue growth. It is also indirectly involved in the lobuloalveolar component, by increasing progesterone receptor expression in
3277-488: Is different. These tissues are not able to synthesize C19 steroids, and therefore depend on C19 supplies from other tissues and the level of aromatase. In females, synthesis of estrogens starts in theca interna cells in the ovary, by the synthesis of androstenedione from cholesterol . Androstenedione is a substance of weak androgenic activity which serves predominantly as a precursor for more potent androgens such as testosterone as well as estrogen. This compound crosses
3390-528: Is expressed in specific tissues including the ovary, uterus and breast. The metabolic effects of estrogen in postmenopausal women have been linked to the genetic polymorphism of the ER. While estrogens are present in both men and women , they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sexual characteristics , such as breasts , darkening and enlargement of nipples , and thickening of
3503-547: Is in line with its Th2 bias. Activity of basophils , eosinophils , M2 macrophages and is enhanced, whereas activity of NK cells is downregulated. Conventional dendritic cells are biased towards Th2 under the influence of estrogen, whereas plasmacytoid dendritic cells, key players in antiviral defence, have increased IFN-g secretion. Estrogen also influences B cells by increasing their survival, proliferation, differentiation and function, which corresponds with higher antibody and B cell count generally detected in women. On
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3616-499: Is known about that history. It has been speculated that circumcision originated as a substitute for castration of defeated enemies or as a religious sacrifice . In many traditions, it acts as a rite of passage marking a boy's entrance into adulthood . At Oued Djerat , in Algeria , engraved rock art with masked bowmen, which feature male circumcision and may be a scene involving ritual, have been dated to earlier than 6000 BP amid
3729-573: Is meatal stenosis, this is almost exclusively seen in circumcised children, it is thought to be caused by ammonia producing bacteria coming into contact with the meatus in circumcised infants. It can be treated by meatotomy . Effective pain management should be used during the procedure. Inadequate pain relief may carry the risks of heightened pain response for newborns. Newborns that experience pain due to being circumcised have different responses to vaccines given afterwards, with higher pain scores observed. For adult men who have been circumcised, there
3842-417: Is needed. For adults, topical anesthesia , ring block, dorsal penile nerve block (DPNB) and general anesthesia are all options, and the procedure requires four to six weeks of abstinence from masturbation or intercourse to allow the wound to heal. Male circumcision reduces the risk of human immunodeficiency virus (HIV) transmission from HIV positive women to men in high risk populations. In 2020,
3955-458: Is not known with certainty, but the oldest documentation comes from ancient Egypt . Around half of all circumcisions worldwide are performed for reasons of prophylactic healthcare. There is a consensus among the world's major medical organizations and in the academic literature that circumcision is an efficacious intervention for HIV prevention in high-risk populations if carried out by medical professionals under safe conditions. In 2007,
4068-496: Is not uniformly favorable and is dependent on the timing of the dose and the type of cognitive skill being measured. The protective effects of estrogens on cognition may be mediated by estrogen's anti-inflammatory effects in the brain. Studies have also shown that the Met allele gene and level of estrogen mediates the efficiency of prefrontal cortex dependent working memory tasks. Researchers have urged for further research to illuminate
4181-733: Is the case of the effect of male sex hormone - testosterone. Indeed, women respond better to vaccines , infections and are generally less likely to develop cancer , the tradeoff of this is that they are more likely to develop an autoimmune disease . The Th2 shift manifests itself in a decrease of cellular immunity and increase in humoral immunity ( antibody production) shifts it from cellular to humoral by downregulating cell-mediated immunity and enhancing Th2 immune response by stimulating IL-4 production and Th2 differentiation. Type 1 and type 17 immune responses are downregulated, likely to be at least partially due to IL-4 , which inhibits Th1. Effect of estrogen on different immune cells' cell types
4294-407: Is the inability to retract the foreskin over the glans penis. At birth, the foreskin cannot be retracted due to adhesions between the foreskin and glans, and this is considered normal (physiological phimosis). Over time the foreskin naturally separates from the glans, and a majority of boys are able to retract the foreskin by age three. Less than one percent are still having problems at age 18. If
4407-508: Is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol. Thus, estradiol is the most important estrogen in non-pregnant females who are between the menarche and menopause stages of life. However, during pregnancy this role shifts to estriol, and in postmenopausal women estrone becomes
4520-415: Is typically triggered by low estrogen levels, and is often mistaken for premenstrual dysphoric disorder . Compulsions in male lab mice, such as those in obsessive-compulsive disorder (OCD), may be caused by low estrogen levels. When estrogen levels were raised through the increased activity of the enzyme aromatase in male lab mice, OCD rituals were dramatically decreased. Hypothalamic protein levels in
4633-933: The Bubaline Period ; more specifically, while possibly dating much earlier than 10,000 BP, rock art walls from the Bubaline Period have been dated between 9200 BP and 5500 BP. The cultural practice of circumcision may have spread from the Central Sahara , toward the south in Sub-Saharan Africa and toward the east in the region of the Nile . Based on engraved evidence found on walls and evidence from mummies , circumcision has been dated to at least as early as 6000 BCE in ancient Egypt . Some ancient Egyptian mummies , which have been dated as early as 4000 BCE, show evidence of circumcision. Evidence suggests that circumcision
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4746-638: The Quran (early seventh century CE), circumcision is considered essential to Islam, and it is nearly universally performed among Muslims. The practice of circumcision spread across the Middle East, North Africa, and Southern Europe with Islam. Genghis Khan and the following Yuan Emperors in China forbade Islamic practices such as halal butchering and circumcision. Estrogen Estrogen (also spelled oestrogen in British English ; see spelling differences )
4859-475: The World Health Organization (WHO) reiterated that male circumcision is an efficacious intervention for HIV prevention if carried out by medical professionals under safe conditions. Human papillomavirus (HPV) is the most commonly transmitted sexually transmitted infection , affecting both men and women. While most infections are asymptomatic and are cleared by the immune system , some types of
4972-669: The basal membrane into the surrounding granulosa cells, where it is converted either immediately into estrone, or into testosterone and then estradiol in an additional step. The conversion of androstenedione to testosterone is catalyzed by 17β-hydroxysteroid dehydrogenase (17β-HSD), whereas the conversion of androstenedione and testosterone into estrone and estradiol, respectively is catalyzed by aromatase, enzymes which are both expressed in granulosa cells. In contrast, granulosa cells lack 17α-hydroxylase and 17,20-lyase , whereas theca cells express these enzymes and 17β-HSD but lack aromatase. Hence, both granulosa and theca cells are essential for
5085-457: The brain have neuroprotective effects. Estrogen regulates the transcription of DNA base excision repair genes as well as the translocation of the base excision repair enzymes between different subcellular compartments. Estrogens are involved in libido (sex drive) in both women and men. Verbal memory scores are frequently used as one measure of higher level cognition . These scores vary in direct proportion to estrogen levels throughout
5198-481: The catechol estrogens 2-hydroxyestradiol , 2-hydroxyestrone , 4-hydroxyestradiol , and 4-hydroxyestrone , as well as 16α-hydroxyestrone , are also estrogens with varying degrees of activity. The biological importance of these minor estrogens is not entirely clear. The actions of estrogen are mediated by the estrogen receptor (ER), a dimeric nuclear protein that binds to DNA and controls gene expression . Like other steroid hormones, estrogen enters passively into
5311-592: The cell membrane . Once inside the cell, they bind to and activate estrogen receptors (ERs) which in turn modulate the expression of many genes . Additionally, estrogens bind to and activate rapid-signaling membrane estrogen receptors (mERs), such as GPER (GPR30). In addition to their role as natural hormones, estrogens are used as medications , for instance in menopausal hormone therapy , hormonal birth control and feminizing hormone therapy for transgender women , intersex people, and nonbinary people . Synthetic and natural estrogens have been found in
5424-669: The endometrium and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the reproductive system important to the maturation of sperm and may be necessary for a healthy libido . Estrogens are responsible for the development of female secondary sexual characteristics during puberty , including breast development , widening of the hips , and female fat distribution . Conversely, androgens are responsible for pubic and body hair growth , as well as acne and axillary odor . Estrogen, in conjunction with growth hormone (GH) and its secretory product insulin-like growth factor 1 (IGF-1),
5537-543: The ovaries , and during pregnancy, the placenta . Follicle-stimulating hormone (FSH) stimulates the ovarian production of estrogens by the granulosa cells of the ovarian follicles and corpora lutea . Some estrogens are also produced in smaller amounts by other tissues such as the liver , pancreas , bone , adrenal glands , skin , brain , adipose tissue , and the breasts . These secondary sources of estrogens are especially important in postmenopausal women. The pathway of estrogen biosynthesis in extragonadal tissues
5650-413: The prophylactic efficacy of the elective circumcision of minors in the context of developed countries . Literature on the matter is polarized, with the cost-benefit analysis being highly dependent on the kinds and frequencies of health problems in the population under discussion and how circumcision affects them. The World Health Organization (WHO), UNAIDS , and American medical organizations take
5763-421: The "John/Joan case", describing apparently successful female gender development, even after David informed his father at age 14 that he had always felt that he was a boy, bringing the experiment to an end. According to John Colapinto , who published a biography of Reimer in 2001, the sessions with Money included what Money called "childhood sexual rehearsal play". Money theorized that reproductive behaviour formed
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#17328523202915876-609: The Canadian news program This Hour Has Seven Days , during which he discussed his theories about gender. At that time, surgical construction of the vagina was more advanced than construction of the penis , and Money believed that Reimer would be happiest in adulthood living as a woman with functioning genitalia. Money and the Hopkins family team persuaded the baby's parents that sex reassignment surgery would be in Reimer's best interest. At
5989-502: The DPNB. They are more effective than EMLA (eutectic mixture of local anesthetics) cream, which is more effective than a placebo . Topical creams have been found to irritate the skin of low birth weight infants, so penile nerve block techniques are recommended in this group. For infants, non-pharmacological methods such as the use of a comfortable, padded chair and a sucrose or non-sucrose pacifier are more effective at reducing pain than
6102-492: The Egyptians for hygienic reasons, but also was part of their obsession with purity and was associated with spiritual and intellectual development. No well-accepted theory explains the significance of circumcision to the Egyptians, but it appears to have been endowed with great honor and importance as a rite of passage , performed in a public ceremony emphasizing the continuation of family generations and fertility. It may have been
6215-708: The Greeks and later the Romans very difficult. Restrictions on the Jewish practice by European governments have occurred several times in world history, including the Seleucid Empire under Antiochus IV and the Roman Empire under Hadrian , where it was used as a means of forceful assimilation and conversion . Antiochus IV's restriction on Jewish circumcision was a major factor in the Maccabean Revolt . Hadrian 's prohibition has also been considered by some to have been
6328-469: The USA. These follow the same basic procedure. First, the amount of foreskin to be removed is estimated. The practitioner opens the foreskin via the preputial orifice to reveal the glans underneath and ensures it is normal before bluntly separating the inner lining of the foreskin ( preputial epithelium ) from its attachment to the glans. The practitioner then places the circumcision device (this sometimes requires
6441-518: The United States. Minor complications are reported to occur in three percent of procedures. Severe complications are rare. A specific complication rate is difficult to determine due to scant data on complications and inconsistencies in their classification. Complication rates are greater when the procedure is performed by an inexperienced operator, in unsterile conditions, or when the child is at an older age. Significant acute complications happen rarely, occurring in about 1 in 500 newborn procedures in
6554-579: The United States. Severe to catastrophic complications, including death, are so rare that they are reported only as individual case reports. Where a Plastibell device is used, the most common complication is the retention of the device occurring in around 3.5% of procedures. Other possible complications include buried penis , chordee , phimosis, skin bridges , urethral fistulas, and meatal stenosis . These complications may be partly avoided with proper technique, and are often treatable without requiring surgical revision. The most common long-term complication
6667-486: The WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS) stated that they recommended adolescent and adult circumcision as part of a comprehensive program for prevention of HIV transmission in areas with high endemic rates of HIV, as long as the program includes " informed consent , confidentiality , and absence of coercion " — known as voluntary medical male circumcision, or VMMC. In 2010, this
6780-444: The age of 22 months, David underwent a bilateral orchiectomy , in which his testes were surgically removed and a rudimentary vulva was constructed by genital plastic surgery . David was reassigned to be raised as female and given the name Brenda (similar to his birth name, "Bruce"). Psychological support for the reassignment and surgery was provided by John Money, who continued to see Reimer annually for consultations and to assess
6893-499: The brain) play an important role in psychosexual differentiation, for example, by masculinizing territorial behavior; the same is not true in humans. In humans, the masculinizing effects of prenatal androgens on behavior (and other tissues, with the possible exception of effects on bone) appear to act exclusively through the androgen receptor. Consequently, the utility of rodent models for studying human psychosexual differentiation has been questioned. Estrogens are responsible for both
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#17328523202917006-718: The breasts and by inducing the secretion of prolactin . Allowed for by estrogen, progesterone and prolactin work together to complete lobuloalveolar development during pregnancy. Androgens such as testosterone powerfully oppose estrogen action in the breasts, such as by reducing estrogen receptor expression in them. Estrogens are responsible for maturation and maintenance of the vagina and uterus , and are also involved in ovarian function, such as maturation of ovarian follicles . In addition, estrogens play an important role in regulation of gonadotropin secretion . For these reasons, estrogens are required for female fertility . Estrogen regulated DNA repair mechanisms in
7119-673: The carcinoma in situ (CIS) cancerous precursor stage and at the more advanced invasive squamous cell carcinoma stage. There is an association between adult circumcision and an increased risk of invasive penile cancer; this is believed to be from men being circumcised as a treatment for penile cancer or a condition that is a precursor to cancer rather than a consequence of circumcision itself. Penile cancer has been observed to be nearly eliminated in populations of males circumcised neonatally. Important risk factors for penile cancer include phimosis and HPV infection, both of which are mitigated by circumcision. The mitigating effect circumcision has on
7232-413: The cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences called a hormone response element to activate the transcription of target genes (in a study using an estrogen-dependent breast cancer cell line as model, 89 such genes were identified). Since estrogen enters all cells, its actions are dependent on the presence of the ER in the cell. The ER
7345-562: The death of his brother Brian from an overdose of antidepressants on 1 July 2002. On 2 May 2004, his wife Jane told him she wanted to separate. On the morning of 4 May 2004, Reimer drove to a grocery store's parking lot in his hometown of Winnipeg and shot himself in the head. He was 38 years old. He and Brian are buried in St. Vital Cemetery in Winnipeg. Money never commented publicly on Colapinto's book or on Reimer's suicide, although colleagues said he
7458-436: The delicate balance between fighting infections and protecting arteries from damage thus lowering the risk of cardiovascular disease. During pregnancy , high levels of estrogens increase coagulation and the risk of venous thromboembolism . Estrogen has been shown to upregulate the peptide hormone adropin . The effect of estrogen on the immune system is in general described as Th2 favoring, rather than suppressive, as
7571-604: The developing evidence that Reimer's reassignment to female was not going well. The BBC science series Horizon based two episodes on his life. "The Boy Who Was Turned into a Girl" aired in 2000 and "Dr Money and the Boy with No Penis" in 2004. A 2001 episode of the PBS documentary series Nova entitled "Sex: Unknown" investigated David's life and the theory behind the decision to raise him as female. An episode of BBC Radio 4 Mind Changers , "Case Study: John/Joan—The Boy Who Was Raised as
7684-408: The development of phimosis. Phimosis is also a complication that can result from circumcision. An inflammation of the glans penis and foreskin is called balanoposthitis, and the condition affecting the glans alone is called balanitis . Most cases of these conditions occur in uncircumcised males, affecting 4–11% of that group. The moist, warm space underneath the foreskin is thought to facilitate
7797-500: The elder of identical twin boys. He was originally named Bruce, and his identical twin was named Brian. Their parents were Janet and Ron Reimer, a couple of Mennonite descent who had married in December 1964. At the age of six months, after concern was raised about how both of them urinated, the boys were diagnosed with phimosis . They were referred for circumcision at the age of seven months. General practitioner Jean-Marie Huot performed
7910-530: The environment and are referred to as xenoestrogens . Estrogens are among the wide range of endocrine-disrupting compounds (EDCs) and can cause health issues and reproductive disfunction in both wildlife and humans. The four major naturally occurring estrogens in women are estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4). Estradiol (E2) is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. During menopause , estrone
8023-525: The foundation of gender, and that "play at thrusting movements and copulation" was a key aspect of gender development in all primates. Starting at age six, according to Brian, the twins were forced to act out sexual acts, with David playing the female role—Money made David get down on all fours, and Brian was forced to "come up behind [him] and place his crotch against [his] buttocks". Money also forced David, in another sexual position, to have his "legs spread" with Brian on top. On "at least one occasion" Money took
8136-580: The fulfillment of a Biblical commandment but also an essential and permanent mark of membership in a people. A narrative in the Christian Gospel of Luke makes a brief mention of the circumcision of Jesus , but physical circumcision is not part of the received teachings of Jesus. Circumcision has played an important role in Christian history and theology . Paul the Apostle reinterpreted circumcision as
8249-404: The gene COMT are enhanced by increasing estrogen levels which are believed to return mice that displayed OCD rituals to normal activity. Aromatase deficiency is ultimately suspected which is involved in the synthesis of estrogen in humans and has therapeutic implications in humans having obsessive-compulsive disorder. Local application of estrogen in the rat hippocampus has been shown to inhibit
8362-445: The growth of pathogens, particularly when hygiene is poor. Yeasts, especially Candida albicans , are the most common penile infection and are rarely identified in samples taken from circumcised males. Both conditions are usually treated with topical antibiotics (metronidazole cream) and antifungals (clotrimazole cream) or low-potency steroid creams. Circumcision is a treatment option for refractory or recurrent balanoposthitis, but in
8475-454: The inability to do so becomes problematic (pathological phimosis) circumcision is a treatment option. This pathological phimosis may be due to scarring from the skin disease balanitis xerotica obliterans (BXO), repeated episodes of balanoposthitis or forced retraction of the foreskin. Steroid creams are also a reasonable option and may prevent the need for surgery including in those with mild BXO. The procedure may also be used to prevent
8588-437: The incidence of cancer-causing forms of human papillomavirus (HPV) and significantly reducing HIV transmission among heterosexual men in high-risk populations; its prophylactic efficacy against HIV transmission in the developed world or among men who have sex with men is debated. Neonatal circumcision decreases the risk of penile cancer . Complication rates increase significantly with age. Bleeding, infection, and
8701-510: The incidence of UTIs in boys under two years of age, and there is fair evidence that the reduction in incidence is by a factor of 3–10 times (100 circumcisions prevents one UTI). Circumcision is most likely to benefit boys who have a high risk of UTIs due to anatomical defects, and may be used to treat recurrent UTIs. There is a plausible biological explanation for the reduction in UTI risk after circumcision. The orifice through which urine passes at
8814-736: The lands south and east of the Mediterranean, starting with Central Sahara, Sudan and Ethiopia, the procedure was practiced by the ancient Egyptians and the Semites , and then by the Jews and Muslims. In Oceania, circumcision is practiced by the Australian Aboriginals and Polynesians . There is also evidence that circumcision was practiced among the Aztec and Mayan civilizations in the Americas, but little
8927-413: The likelihood of multiple infections. As of 2012 , there was no strong evidence that it reduces the rate of new HPV infection, but the procedure is associated with increased clearance of the virus by the body, which can account for the finding of reduced prevalence. Although genital warts are caused by a type of HPV, there is no statistically significant relationship between being circumcised and
9040-400: The menstrual cycle, pregnancy, and menopause. Furthermore, estrogens when administered shortly after natural or surgical menopause prevents decreases in verbal memory. In contrast, estrogens have little effect on verbal memory if first administered years after menopause. Estrogens also have positive influences on other measures of cognitive function. However the effect of estrogens on cognition
9153-429: The mid- luteal phase . It is hypothesized that these changes occur due to brain changes across the menstrual cycle that are likely a genomic effect of hormones. These effects produce menstrual cycle changes, which result in hormone release leading to behavioral changes, notably binge and emotional eating. These occur especially prominently among women who are genetically vulnerable to binge eating phenotypes. Binge eating
9266-559: The neonatal period when it is less expensive and has a lower risk of complications. The American Academy of Pediatrics and Centers for Disease Control and Prevention stated that the potential benefits of circumcision outweigh the risks. The World Health Organization in 2010 stated: There are significant benefits in performing male circumcision in early infancy, and programmes that promote early infant male circumcision are likely to have lower morbidity rates and lower costs than programmes targeting adolescent boys and men. Circumcision
9379-454: The neurotransmitter serotonin in the cerebrospinal fluid. Estrogen works to activate 5-HT neurons, leading to suppression of binge like eating behaviors. It is also suggested that there is an interaction between hormone levels and eating at different points in the female menstrual cycle . Research has predicted increased emotional eating during hormonal flux, which is characterized by high progesterone and estradiol levels that occur during
9492-486: The operation using the unconventional method of electrocauterization , but the procedure burned David's penis beyond surgical repair. The doctors chose not to operate on Brian, whose phimosis soon cleared without surgical intervention. The parents, concerned about their son's prospects for future happiness and sexual function without a penis, took him to Johns Hopkins Hospital in Baltimore in early 1967 to see John Money ,
9605-558: The outcome in order to dissuade physicians from treating other infants similarly. Soon after, Reimer went public with his story and John Colapinto published a widely disseminated and influential account in Rolling Stone magazine in December 1997. The article won the National Magazine Award for Reporting. This was later expanded into The New York Times best-selling biography As Nature Made Him: The Boy Who Was Raised as
9718-528: The outcome. This reassignment was considered an especially important test case of the social learning concept of gender identity for two reasons: first, Reimer's identical twin brother, Brian, made an ideal control because the brothers shared genes, family environments, and the intrauterine environment; second, this was reputed to be the first reassignment and reconstruction performed on a male infant who had no abnormality of prenatal or early postnatal sexual differentiation . Money reported on Reimer's progress as
9831-426: The penis ( chordee ), or ambiguous genitalia , because the foreskin may be needed for reconstructive surgery. Circumcision is contraindicated in premature infants and those who are not clinically stable and in good health. If an individual is known to have or has a family history of serious bleeding disorders such as hemophilia , it is recommended that the blood be checked for normal coagulation properties before
9944-408: The position that it carries prophylactic health benefits which outweigh the risks, while European medical organizations generally hold the belief that in these situations its medical benefits are not counterbalanced by risk. Advocates of circumcision consider it to have a net health benefit, and therefore feel that increasing the circumcision rate is "imperative". They recommend performing it during
10057-726: The presence of genital warts. Studies evaluating the effect of circumcision on the rates of other sexually transmitted infections have, generally, found it to be protective. A 2006 meta-analysis found that circumcision was associated with lower rates of syphilis , chancroid , and possibly genital herpes . A 2010 review found that circumcision reduced the incidence of HSV -2 (herpes simplex virus, type 2) infections by 28%. The researchers found mixed results for protection against trichomonas vaginalis and chlamydia trachomatis , and no evidence of protection against gonorrhea or syphilis. It may also possibly protect against syphilis in MSM. Phimosis
10170-639: The primary form of estrogen in the body. Another type of estrogen called estetrol (E4) is produced only during pregnancy. All of the different forms of estrogen are synthesized from androgens , specifically testosterone and androstenedione , by the enzyme aromatase . Minor endogenous estrogens, the biosyntheses of which do not involve aromatase , include 27-hydroxycholesterol , dehydroepiandrosterone (DHEA), 7-oxo-DHEA , 7α-hydroxy-DHEA , 16α-hydroxy-DHEA , 7β-hydroxyepiandrosterone , androstenedione (A4), androstenediol (A5), 3α-androstanediol , and 3β-androstanediol . Some estrogen metabolites, such as
10283-509: The procedure is attempted. The foreskin is the double-layered fold of tissue at the distal end of the human penis that covers the glans and the urinary meatus . For adult medical circumcision, superficial wound healing takes up to a week, and complete healing 4 to 6 months. For infants, healing is usually complete within one week. For infant circumcision, devices such as the Gomco clamp , Plastibell and Mogen clamp are commonly used in
10396-705: The production of estrogen in the ovaries. Estrogen levels vary through the menstrual cycle , with levels highest near the end of the follicular phase just before ovulation . Note that in males, estrogen is also produced by the Sertoli cells when FSH binds to their FSH receptors. Estrogens are plasma protein bound to albumin and/or sex hormone-binding globulin in the circulation. Estrogens are metabolized via hydroxylation by cytochrome P450 enzymes such as CYP1A1 and CYP3A4 and via conjugation by estrogen sulfotransferases ( sulfation ) and UDP-glucuronyltransferases ( glucuronidation ). In addition, estradiol
10509-527: The pubertal growth spurt, which causes an acceleration in linear growth, and epiphyseal closure , which limits height and limb length, in both females and males. In addition, estrogens are responsible for bone maturation and maintenance of bone mineral density throughout life. Due to hypoestrogenism, the risk of osteoporosis increases during menopause . Women are less impacted by heart disease due to vasculo-protective action of estrogen which helps in preventing atherosclerosis. It also helps in maintaining
10622-514: The re-uptake of serotonin . Contrarily, local application of estrogen has been shown to block the ability of fluvoxamine to slow serotonin clearance, suggesting that the same pathways which are involved in SSRI efficacy may also be affected by components of local estrogen signaling pathways. Studies have also found that fathers had lower levels of cortisol and testosterone but higher levels of estrogen (estradiol) than did non-fathers. Estrogen may play
10735-456: The removal of either too much or too little foreskin are the most common acute complications, while meatal stenosis is the most common long-term. There are various cultural, social , and ethical views on circumcision. Major medical organizations hold variant views on the strength of circumcision's prophylactic efficacy in developed countries. Some medical organizations take the position that it carries prophylactic health benefits which outweigh
10848-526: The rise of the anti-gender movement . Diamond's report and Colapinto's subsequent book about Reimer influenced several medical practices, reputations, and even current understanding of the biology of gender . The case accelerated the decline of sex reassignment and surgery for unambiguous XY infants with micropenis , various other rare congenital malformations, or penile loss in infancy. Colapinto's book described unethical and traumatic childhood therapy sessions and implied that Money had ignored or concealed
10961-407: The risk factor introduced by the possibility of phimosis is secondary, in that the removal of the foreskin eliminates the possibility of phimosis. This can be inferred from study results that show uncircumcised men with no history of phimosis are equally likely to have penile cancer as circumcised men. Circumcision is also associated with a reduced prevalence of cancer-causing types of HPV in men and
11074-483: The risks, while other medical organizations generally hold the belief that in these situations its medical benefits are not counterbalanced by risk. Circumcision is one of the world's most common and oldest medical procedures. Prophylactic usage originated in England during the 1850s and subsequently widely spread, becoming predominately established as a way to prevent sexually transmitted infections. Beyond use as
11187-535: The role of estrogen and its potential for improvement on cognitive function. Estrogen is considered to play a significant role in women's mental health . Sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained low estrogen levels correlate with a significant lowering of mood. Clinical recovery from postpartum , perimenopause , and postmenopause depression has been shown to be effective after levels of estrogen were stabilized and/or restored. Menstrual exacerbation (including menstrual psychosis)
11300-490: The same story. Estrogen was given to David during adolescence, therefore inducing breast development . For several years, Money reported on Reimer's progress as the "John/Joan case". Money wrote, "The child's behavior is so clearly that of an active little girl and so different from the boyish ways of her twin brother." The twins attended Glenwood School in Winnipeg, and from the age of 14, David attended R.B. Russell Vocational High School . He eventually ceased attending
11413-443: The school and was tutored privately. By the age of 13 years, Reimer was experiencing suicidal depression and he told his parents he would take his own life if they made him see Money again. Finally, on 14 March 1980, Reimer's parents told him the truth about his sex reassignment, following advice from Reimer's endocrinologist and psychiatrist . At the age of 14, having been informed of his past by his father, Reimer decided to assume
11526-403: The sexual pleasure of the circumcised person. Neonatal circumcision is generally a safe, low-risk procedure when done by an experienced practitioner. The most common acute complications are bleeding, infection and the removal of either too much or too little foreskin. These complications occur in approximately 0.13% of procedures, with bleeding being the most common acute complication in
11639-432: The tip of the penis (the urinary meatus ) hosts more urinary system disease-causing bacteria in uncircumcised boys than in circumcised boys, especially in those under six months of age. As these bacteria are a risk factor for UTIs, circumcision may reduce the risk of UTIs through a decrease in the bacterial population. Not being circumcised is the primary risk factor for penile cancer . Pre-adolescent circumcision has
11752-404: The twenty-first century the availability of the other treatments has made it less necessary. A UTI affects parts of the urinary system including the urethra , bladder , and kidneys . There is about a one percent risk of UTIs in boys under two years of age, and the majority of incidents occur in the first year of life. There is good but not ideal evidence that circumcision of babies reduces
11865-407: The use of analgesia is advocated. Ordinary procedural pain may be managed in pharmacological and non-pharmacological ways. Pharmacological methods, such as localized or regional pain-blocking injections and topical analgesic creams, are safe and effective. The ring block and dorsal penile nerve block (DPNB) are the most effective at reducing pain, and the ring block may be more effective than
11978-492: The virus cause genital warts , and other types, if untreated, cause various forms of cancer, including cervical cancer and penile cancer . Genital warts and cervical cancer are the two most common problems resulting from HPV. Circumcision is associated with a reduced prevalence of oncogenic types of HPV infection, meaning that a randomly selected circumcised man is less likely to be found infected with cancer-causing types of HPV than an uncircumcised man. It also decreases
12091-511: Was "mortified" by the case. For the first 30 years after Money's initial report that the reassignment had been a success, Money's view of the malleability of gender became the dominant viewpoint in the field, reassuring practitioners that sexual reassignment was the correct decision in certain instances. Money claimed the success of Reimer's gender transition as support for the optimum gender rearing model for intersex children. Researcher Mary Anne Case argues that Money's view on gender also fuelled
12204-702: Was also documented (termed membrane-initiated steroid signalling, MISS). This pathway stimulates the ERK and PI3K/AKT pathways, which are known to increase cellular proliferation and affect chromatin remodelation. Researchers have implicated estrogens in various estrogen-dependent conditions , such as ER-positive breast cancer , as well as a number of genetic conditions involving estrogen signaling or metabolism, such as estrogen insensitivity syndrome , aromatase deficiency , and aromatase excess syndrome . High estrogen can amplify stress-hormone responses in stressful situations. Estrogens, in females, are produced primarily by
12317-533: Was expanded to routine neonatal circumcision, as long as those undergoing the procedure received assent from their parents. In 2020, the World Health Organization again concluded that male circumcision is an efficacious intervention for HIV prevention and that the promotion of male circumcision is an essential strategy, in addition to other preventive measures, for the prevention of heterosexually acquired HIV infection in men. Eastern and southern Africa had
12430-487: Was going to give me a whupping. So I took my clothes off and stood there shaking." Money's rationale for these various treatments was his belief that "childhood 'sexual rehearsal play ' " was important for a "healthy adult gender identity". Both David and Brian were traumatized with Brian speaking about it "only with the greatest emotional turmoil", and David unwilling to speak about the details publicly, although his wife, Jane Fontane, stated that David had privately told her
12543-470: Was less consistent in regards to the potential association of circumcision with women's risk of HPV and HIV. The accumulated data show circumcision does not have an adverse physiological effect on sexual pleasure, function, desire, or fertility. There is some evidence that circumcision has no effect on pain with intercourse , premature ejaculation , intravaginal ejaculation latency time , erectile dysfunction or difficulties with orgasm . According to
12656-476: Was not a girl occurred between the ages of 9 and 11 years and that he was living as a male by the age of 15. Well known in medical circles for years anonymously as the "John/Joan" case, Reimer later went public with his story to help discourage similar medical practices. He killed himself at age 38, two days after being petitioned for divorce by his wife. David Reimer was born in Winnipeg , Manitoba, on 22 August 1965,
12769-554: Was practiced in the Middle East by the fourth millennium BCE, when the Sumerians and the Semites moved into the area that is modern-day Iraq from the North and West. The earliest historical record of circumcision comes from Egypt, in the form of an image of the circumcision of an adult carved into the tomb of Ankh-Mahor at Saqqara , dating to about 2400–2300 BCE. Circumcision was possibly done by
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