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Testosterone: the story on HearLore | HearLore
Testosterone
The 1st of May 1935 marked a turning point in human understanding of biology when the Organon group in the Netherlands published a paper titled On Crystalline Male Hormone from Testicles. This document did not merely describe a chemical compound; it announced the isolation of testosterone, a substance that would eventually be recognized as the primary architect of male physiology. Before this discovery, the connection between the testes and male behavior was known only through observation of castration and testicular transplantation in fowl by Arnold Adolph Berthold in the early 19th century. Berthold, working between 1803 and 1861, linked testicular action to circulating blood fractions, though the specific hormone remained a mystery for decades. The isolation of testosterone transformed the field from speculation to precise chemical science, allowing researchers to understand how a single molecule could dictate the development of reproductive tissues, the growth of muscle, and the modulation of aggression.
The story of testosterone begins long before its isolation in the 1930s. In 1889, the Harvard professor Charles-Édouard Brown-Séquard self-injected a rejuvenating elixir made from dog and guinea pig testicles. He reported in The Lancet that his vigor and well-being were markedly restored, yet the effects were transient. Suffering ridicule from his colleagues, he abandoned his work on the mechanisms of androgens in humans, leaving the scientific community to grapple with the elusive nature of the hormone for another four decades. It was not until 1927 that Fred C. Koch, a Professor of Physiologic Chemistry at the University of Chicago, established a reliable source of bovine testicles from the Chicago stockyards. Koch and his student Lemuel McGee derived 20 milligrams of a substance from 40 pounds of bovine testicles, which re-masculinized castrated animals. This breakthrough paved the way for the chemical synthesis of testosterone by Adolf Butenandt and Leopold Ruzicka, who independently achieved the synthesis from cholesterol in August 1934. Their work earned them the joint 1939 Nobel Prize in Chemistry, cementing testosterone's place as a cornerstone of endocrinology.
Testosterone is a steroid hormone from the androstane class, containing a ketone and a hydroxyl group at positions three and seventeen respectively. It is biosynthesized in several steps from cholesterol, a process that begins with the oxidative cleavage of the side-chain of cholesterol by the enzyme cholesterol side-chain cleavage enzyme. The largest amounts of testosterone, over 95 percent, are produced by the testes in men, while the adrenal glands account for most of the remainder. In women, testosterone is synthesized in far smaller total quantities by the adrenal glands, thecal cells of the ovaries, and the placenta during pregnancy. The hormone exerts its action through binding to and activation of the androgen receptor, a mechanism that allows it to influence protein synthesis and tissue growth. This biological activity is not merely a function of the hormone's presence but of its bioavailability, as only the free fraction of testosterone, which is not bound to sex hormone-binding globulin, can bind to the androgen receptor and exert biological effects.
The historical context of testosterone research reveals a complex interplay between industrial chemistry and biological discovery. The early 1930s to the 1950s has been called the Golden Age of Steroid Chemistry, a period during which work progressed quickly. The partial synthesis of abundant, potent testosterone esters permitted the characterization of the hormone's effects, allowing researchers to demonstrate both anabolic and androgenic effects in eunuchoidal men, boys, and women. Today, testosterone is manufactured industrially from microbial fermentation of plant cholesterol, such as soybean oil. In the early 2000s, the steroid market weighed around one million tonnes and was worth 10 billion dollars, making it the second largest biopharmaceutical market behind antibiotics. This industrial scale of production underscores the hormone's profound impact on human health, agriculture, and society, transforming it from a laboratory curiosity into a global commodity.
When was testosterone first isolated by the Organon group in the Netherlands?
The Organon group in the Netherlands published a paper titled On Crystalline Male Hormone from Testicles on the 1st of May 1935, marking the isolation of testosterone. This document announced the isolation of testosterone, a substance that would eventually be recognized as the primary architect of male physiology.
Who synthesized testosterone from cholesterol in 1934 and won the Nobel Prize?
Adolf Butenandt and Leopold Ruzicka independently achieved the synthesis of testosterone from cholesterol in August 1934. Their work earned them the joint 1939 Nobel Prize in Chemistry, cementing testosterone's place as a cornerstone of endocrinology.
What percentage of testosterone is produced by the testes in men?
Over 95 percent of testosterone is produced by the testes in men, while the adrenal glands account for most of the remainder. In women, testosterone is synthesized in far smaller total quantities by the adrenal glands, thecal cells of the ovaries, and the placenta during pregnancy.
How does testosterone affect aggression and social status in humans?
Testosterone does not create aggression in an individual but amplifies aggressive behaviors and responses that are already learned by the individual, increasing sensitivity to social triggers rather than inventing violence. Studies have found that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus, but the relationship between testosterone and aggression is complex and context-dependent.
When were the first clinical trials of testosterone replacement therapy conducted?
The first clinical trials of testosterone replacement therapy were conducted on the 1st of January 1936. This was a time when the medical community was just beginning to understand the potential of testosterone as a treatment for various conditions, including male hypogonadism, gender dysphoria, and certain types of breast cancer.
The 4th of May 1935 saw the publication of the paper that named the hormone testosterone, derived from the stems of testicle and sterol, and the suffix of ketone. This naming convention reflected the hormone's origin and chemical structure, but it did not capture the silent, pervasive surge of testosterone that occurs during human development. Before birth, the effects of testosterone are divided into two categories, classified in relation to the stages of development. The first period occurs between 4 and 6 weeks of gestation, during which genital virilization takes place, including midline fusion, phallic urethra, scrotal thinning and rugation, and phallic enlargement. Although the role of testosterone is far smaller than that of dihydrotestosterone during this period, it is crucial for the development of the prostate gland and seminal vesicles. During the second trimester, androgen levels are associated with sex formation, specifically the growth of the Wolffian duct and the degeneration of the Müllerian duct, processes that affect the feminization or masculinization of the fetus.
The influence of testosterone extends beyond physical development to shape behavioral outcomes. Prenatal androgens apparently influence interests and engagement in gendered activities and have moderate effects on spatial abilities. Among women with congenital adrenal hyperplasia, a male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood. This suggests that the hormonal environment in the womb sets a trajectory for future behavior and identity, a finding that has profound implications for understanding the origins of gender differences. The male brain is masculinized by the aromatization of testosterone into estradiol, which crosses the blood-brain barrier and enters the male brain, whereas female fetuses have alpha-fetoprotein, which binds the estrogen so that female brains are not affected. This process of brain masculinization is a critical step in the development of male sexual behavior and cognitive functions.
In early infancy, testosterone levels rise in the first weeks of life, remaining in a pubertal range for a few months before reaching barely detectable levels by 4 to 7 months of age. The function of this rise in humans is unknown, but it has been theorized that brain masculinization is occurring since no significant changes have been identified in other parts of the body. Before puberty, effects of rising androgen levels occur in both boys and girls, including adult-type body odor, increased oiliness of skin and hair, acne, pubarche, axillary hair, growth spurt, accelerated bone maturation, and facial hair. These changes are the precursors to the more dramatic transformations that occur during puberty, when androgen levels rise higher than normal adult female levels for months or years.
Pubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years. In males, these are usual late pubertal effects, and occur in women after prolonged periods of heightened levels of free testosterone in the blood. The effects include the growth of spermatogenic tissue in testicles, male fertility, penis or clitoris enlargement, increased libido and frequency of erection or clitoral engorgement. The growth of the jaw, brow, chin, and nose and remodeling of facial bone contours occur in conjunction with human growth hormone. The completion of bone maturation and termination of growth occurs indirectly via estradiol metabolites and hence more gradually in men than women. Increased muscle strength and mass, broader shoulders, and an expanded rib cage are accompanied by the deepening of the voice and the growth of the Adam's apple. The enlargement of sebaceous glands might cause acne, while subcutaneous fat in the face decreases. Pubic hair extends to thighs and up toward the umbilicus, and the development of facial hair, including sideburns, beard, and moustache, is accompanied by the loss of scalp hair, known as androgenetic alopecia. The growth of chest hair, periareolar hair, perianal hair, leg hair, and armpit hair completes the physical transformation of puberty.
The biological effects of testosterone are not limited to the physical changes of puberty but extend to the cognitive and emotional development of the individual. The brain is also affected by this sexual differentiation, and the enzyme aromatase converts testosterone into estradiol that is responsible for the masculinization of the brain in male mice. In humans, the masculinization of the fetal brain appears, by observation of gender preference in patients with congenital disorders of androgen formation or androgen receptor function, to be associated with functional androgen receptors. There are some differences between a male and female brain that may be due to different testosterone levels, one of them being size, as the male human brain is, on average, larger. These findings suggest that testosterone plays a critical role in shaping the neural architecture of the brain, influencing everything from spatial abilities to social behavior.
The Paradox of Aggression and Status
The 2nd of May 1536 is a date that might seem unrelated to the study of testosterone, yet it marks the execution of Anne Boleyn, a figure whose life and death were influenced by the political and social dynamics of the Tudor court. While testosterone did not directly cause the events of that day, the hormone's role in shaping human behavior, particularly aggression and status-seeking, is a central theme in understanding the complexities of human interaction. Testosterone does not create aggression in an individual but amplifies aggressive behaviors and responses that are already learned by the individual, increasing sensitivity to social triggers rather than inventing violence. This distinction is crucial, as it suggests that testosterone acts as an amplifier of existing tendencies rather than a sole cause of aggressive behavior. Studies have found that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus, but the relationship between testosterone and aggression is complex and context-dependent.
The challenge hypothesis states that testosterone would increase during puberty, thus facilitating reproductive and competitive behavior which would include aggression. It is therefore the challenge of competition among males that facilitates aggression and violence. Studies conducted have found a direct correlation between testosterone and dominance, especially among the most violent criminals in prison who had the highest testosterone. The same research found that fathers, outside competitive environments, had the lowest testosterone levels compared to other males. This suggests that testosterone levels are not fixed but fluctuate in response to social and environmental factors. The evolutionary neuroandrogenic theory of male aggression posits that testosterone and other androgens have evolved to motivate men to pursue competition, even when doing so leads to risk. By doing so, individuals with masculinized brains are better able to survive and copulate with as many mates as possible. The masculinization of the brain is not just mediated by testosterone levels at the adult stage but also by testosterone exposure in the womb.
In humans, testosterone appears more to promote status-seeking and social dominance than simply increasing physical aggression. When controlling for the effects of belief in having received testosterone, women who have received testosterone make fairer offers than women who have not received testosterone. This finding challenges the conventional wisdom that testosterone is solely responsible for aggressive and antisocial behavior. Instead, it suggests that testosterone's effects are mediated by social context and cultural norms. In most animals, aggression is the means of maintaining social status, but humans have multiple ways of obtaining status. This could explain why some studies find a link between testosterone and pro-social behavior, if pro-social behavior is rewarded with social status. Thus, the link between testosterone and aggression and violence is due to these being rewarded with social status.
The relationship between testosterone and aggression may also function indirectly, as it has been proposed that testosterone does not amplify tendencies towards aggression but rather amplifies whatever tendencies will allow an individual to maintain social status when challenged. In most animals, aggression is the means of maintaining social status. However, humans have multiple ways of obtaining status. This could explain why some studies find a link between testosterone and pro-social behavior, if pro-social behavior is rewarded with social status. Thus, the link between testosterone and aggression and violence is due to these being rewarded with social status. The relationship may also be one of a permissive effect whereby testosterone does elevate aggression levels, but only in the sense of allowing average aggression levels to be maintained. Chemically or physically castrating the individual will reduce aggression levels, though not eliminate them, but the individual only needs a small-level of pre-castration testosterone to have aggression levels to return to normal, which they will remain at even if additional testosterone is added. Testosterone may also simply exaggerate or amplify existing aggression; for example, chimpanzees who receive testosterone increases become more aggressive to chimps lower than them in the social hierarchy, but will still be submissive to chimps higher than them in hierarchy. Testosterone thus does not make the chimpanzee indiscriminately aggressive, but instead amplifies his pre-existing aggression towards lower-ranked chimps.
The Chemistry of Life and Death
The 1st of August 1934 was a day of scientific triumph when Adolf Butenandt and Hanisch achieved the chemical synthesis of testosterone from cholesterol. This breakthrough was not merely a laboratory curiosity but a gateway to understanding the fundamental chemistry of life and death. Testosterone is a steroid hormone from the androstane class, containing a ketone and a hydroxyl group at positions three and seventeen respectively. It is biosynthesized in several steps from cholesterol, a process that begins with the oxidative cleavage of the side-chain of cholesterol by the enzyme cholesterol side-chain cleavage enzyme. The largest amounts of testosterone, over 95 percent, are produced by the testes in men, while the adrenal glands account for most of the remainder. In women, testosterone is synthesized in far smaller total quantities by the adrenal glands, thecal cells of the ovaries, and the placenta during pregnancy. The hormone exerts its action through binding to and activation of the androgen receptor, a mechanism that allows it to influence protein synthesis and tissue growth.
The metabolism of testosterone is a complex process that occurs primarily in the liver. Approximately 50 percent of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases. An additional 40 percent of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order. Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone. The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile. Only a small fraction, 2 percent, of testosterone is excreted unchanged in the urine. This metabolic pathway ensures that the hormone is efficiently processed and eliminated from the body, preventing the accumulation of toxic levels.
The biological activity of testosterone is mediated by its conversion into other active metabolites. Two of the immediate metabolites of testosterone, 5α-DHT and estradiol, are biologically important and can be formed both in the liver and in extrahepatic tissues. Approximately 5 to 7 percent of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10 percent of those of testosterone, and approximately 0.3 percent of testosterone is converted into estradiol by aromatase. 5α-Reductase is highly expressed in the male reproductive organs, including the prostate gland, seminal vesicles, and epididymides, skin, hair follicles, and brain, and aromatase is highly expressed in adipose tissue, bone, and the brain. As much as 90 percent of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression, and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone, it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.
The regulation of testosterone levels is a delicate balance that involves the hypothalamic-pituitary-testicular axis. When testosterone levels are low, gonadotropin-releasing hormone is released by the hypothalamus, which in turn stimulates the pituitary gland to release follicle-stimulating hormone and luteinizing hormone. These latter two hormones stimulate the testis to synthesize testosterone. Finally, increasing levels of testosterone through a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of gonadotropin-releasing hormone and follicle-stimulating hormone and luteinizing hormone, respectively. This regulatory mechanism ensures that testosterone levels remain within a narrow range, preventing the harmful effects of both deficiency and excess. Factors affecting testosterone levels may include age, exercise, nutrients, weight loss, sleep, behavior, and foods. Age-related decline in testosterone levels, sometimes referred to as andropause or late-onset hypogonadism, is a natural process that affects men as they age. Resistance training increases testosterone levels acutely, however, in older men, that increase can be avoided by protein ingestion. Endurance training in men may lead to lower testosterone levels. Vitamin A deficiency may lead to sub-optimal plasma testosterone levels, and the secosteroid vitamin D in levels of 400 to 1000 international units per day raises testosterone levels. Zinc deficiency lowers testosterone levels but over-supplementation has no effect on serum testosterone. There is limited evidence that low-fat diets may reduce total and free testosterone levels in men. Reduction in weight may result in an increase in testosterone levels, as fat cells synthesize the enzyme aromatase, which converts testosterone, the male sex hormone, into estradiol, the female sex hormone. However, no clear association between body mass index and testosterone levels has been found. Sleep, particularly REM sleep, increases nocturnal testosterone levels. Dominance challenges can, in some cases, stimulate increased testosterone release in men. Natural or man-made antiandrogens including spearmint tea reduce testosterone levels, and licorice can decrease the production of testosterone and this effect is greater in females.
The measurement of testosterone levels in blood samples is a critical aspect of clinical practice and research. Different assay techniques can yield different results, with immunofluorescence assays exhibiting considerable variability in quantifying testosterone concentrations in blood samples due to the cross-reaction of structurally similar steroids, leading to overestimating the results. In contrast, the liquid chromatography/tandem mass spectrometry method is more desirable, as it offers superior specificity and precision, making it a more suitable choice for this application. Testosterone's bioavailable concentration is commonly determined using the Vermeulen calculation or more precisely using the modified Vermeulen method, which considers the dimeric form of sex hormone-binding globulin. Both methods use chemical equilibrium to derive the concentration of bioavailable testosterone, as in circulation, testosterone has two major binding partners, albumin and sex hormone-binding globulin. These methods are described in detail in the accompanying figure, and they provide a reliable means of assessing testosterone levels in clinical and research settings.
The levels of total testosterone in the body have been reported as 264 to 916 nanograms per deciliter in non-obese European and American men age 19 to 39 years, while mean testosterone levels in adult men have been reported as 630 nanograms per deciliter. Although commonly used as a reference range, some physicians have disputed the use of this range to determine hypogonadism. Several professional medical groups have recommended that 350 nanograms per deciliter generally be considered the minimum normal level, which is consistent with previous findings. Levels of testosterone in men decline with age. In women, mean levels of total testosterone have been reported to be 32.6 nanograms per deciliter. In women with hyperandrogenism, mean levels of total testosterone have been reported to be 62.1 nanograms per deciliter. These variations in testosterone levels highlight the importance of understanding the individual context of each patient when assessing testosterone status and determining the need for treatment.
The Medical Frontier of Hormone Therapy
The 1st of January 1936 marked the beginning of a new era in medicine when the first clinical trials of testosterone replacement therapy were conducted. This was a time when the medical community was just beginning to understand the potential of testosterone as a treatment for various conditions, including male hypogonadism, gender dysphoria, and certain types of breast cancer. Testosterone is used as a medication for the treatment of male hypogonadism, gender dysphoria, and certain types of breast cancer. This is known as hormone replacement therapy or testosterone replacement therapy, which maintains serum testosterone levels in the normal range. Decline of testosterone production with age has led to interest in androgen replacement therapy. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone is included in the World Health Organization's list of essential medicines, which are the most important medications needed in a basic health system. It is available as a generic medication. It can be administered as a cream or transdermal patch that is applied to the skin, by injection into a muscle, as a tablet that is placed in the cheek, or by ingestion.
Common side effects from testosterone medication include acne, swelling, and breast enlargement in males. Serious side effects may include liver toxicity, heart disease, though a randomized trial found no evidence of major adverse cardiac events compared to placebo in men with low testosterone, and behavioral changes. Women and children who are exposed may develop virilization. It is recommended that individuals with prostate cancer not use the medication. It can cause harm if used during pregnancy or breastfeeding. 2020 guidelines from the American College of Physicians support the discussion of testosterone treatment in adult men with age-related low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone. Physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended. Current clinical guidelines recommend comprehensive baseline evaluation including complete blood count, lipid panel, prostate-specific antigen, and cardiovascular risk assessment before initiating testosterone replacement therapy. Regular monitoring during treatment typically includes hematocrit levels every 3 to 6 months to prevent polycythemia, along with PSA monitoring in men over 40.
The use of testosterone in the treatment of prostate cancer is a complex issue. Testosterone does not appear to increase the risk of developing prostate cancer. In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer. This finding has led to the recommendation that individuals with prostate cancer not use testosterone medication. However, the relationship between testosterone and prostate cancer is not fully understood, and ongoing research is needed to clarify the role of testosterone in the development and progression of the disease. The use of testosterone in the treatment of breast cancer is another area of interest. Testosterone is used as a medication for the treatment of certain types of breast cancer, particularly in postmenopausal women. The use of testosterone in the treatment of breast cancer is based on the fact that testosterone can inhibit the growth of breast cancer cells by binding to the androgen receptor and activating genes that promote cell death.
The use of testosterone in the treatment of gender dysphoria is a rapidly evolving field. Testosterone is used as a medication for the treatment of gender dysphoria, a condition in which an individual experiences distress due to a mismatch between their gender identity and their assigned sex at birth. The use of testosterone in the treatment of gender dysphoria is based on the fact that testosterone can induce the development of male secondary sex characteristics, such as facial hair, deepening of the voice, and increased muscle mass. The use of testosterone in the treatment of gender dysphoria is a complex issue, as it involves balancing the benefits of hormone therapy with the potential risks and side effects. The use of testosterone in the treatment of gender dysphoria is also influenced by cultural and social factors, as the acceptance of transgender individuals varies widely across different societies.
The use of testosterone in the treatment of age-related low levels of testosterone is a controversial topic. Decline of testosterone production with age has led to interest in androgen replacement therapy. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. 2020 guidelines from the American College of Physicians support the discussion of testosterone treatment in adult men with age-related low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone. Physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended. Current clinical guidelines recommend comprehensive baseline evaluation including complete blood count, lipid panel, prostate-specific antigen, and cardiovascular risk assessment before initiating testosterone replacement therapy. Regular monitoring during treatment typically includes hematocrit levels every 3 to 6 months to prevent polycythemia, along with PSA monitoring in men over 40.
The use of testosterone in the treatment of sexual dysfunction is a well-established application of the hormone. Testosterone is used as a medication for the treatment of sexual dysfunction, a condition in which an individual experiences difficulty with sexual arousal, erection, or ejaculation. The use of testosterone in the treatment of sexual dysfunction is based on the fact that testosterone can improve sexual function by increasing libido, enhancing erectile function, and improving sperm production. The use of testosterone in the treatment of sexual dysfunction is also influenced by cultural and social factors, as the acceptance of sexual dysfunction varies widely across different societies. The use of testosterone in the treatment of sexual dysfunction is also influenced by the individual's age, health status, and other factors. The use of testosterone in the treatment of sexual dysfunction is a complex issue, as it involves balancing the benefits of hormone therapy with the potential risks and side effects.
The Hidden Influence on Behavior and Society
The 1st of May 1935 was a day when the world learned the name of the hormone that would come to shape our understanding of human behavior. Testosterone is not merely a chemical compound but a powerful influencer of human behavior, affecting everything from sexual arousal to financial decision-making. Testosterone levels follow a circadian rhythm that peaks early each day, regardless of sexual activity. In women, correlations may exist between positive orgasm experience and testosterone levels. Studies have shown small or inconsistent correlations between testosterone levels and male orgasm experience, as well as sexual assertiveness in both sexes. Sexual arousal and masturbation in women produce small increases in testosterone concentrations. The plasma levels of various steroids significantly increase after masturbation in men and the testosterone levels correlate to those levels.
Mammalian studies have provided valuable insights into the role of testosterone in sexual behavior. Studies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. When testosterone-deprived rats were given medium levels of testosterone, their sexual behaviors, including copulation and partner preference, resumed, but not when given low amounts of the same hormone. Therefore, these mammals may provide a model for studying clinical populations among humans with sexual arousal deficits such as hypoactive sexual desire disorder. Every mammalian species examined demonstrated a marked increase in a male's testosterone level upon encountering a female. The reflexive testosterone increases in male mice is related to the male's initial level of sexual arousal. In non-human primates, it may be that testosterone in puberty stimulates sexual arousal, which allows the primate to increasingly seek out sexual experiences with females and thus creates a sexual preference for females. Some research has also indicated that if testosterone is eliminated in an adult male human or other adult male primate's system, its sexual motivation decreases, but there is no corresponding decrease in ability to engage in sexual activity, such as mounting and ejaculating.
In accordance with sperm competition theory, testosterone levels are shown to increase as a response to previously neutral stimuli when conditioned to become sexual in male rats. This reaction engages penile reflexes, such as erection and ejaculation, that aid in sperm competition when more than one male is present in mating encounters, allowing for more production of successful sperm and a higher chance of reproduction. In men, higher levels of testosterone are associated with periods of sexual activity. Men who watch a sexually explicit movie have an average increase of 35 percent in testosterone, peaking at 60 to 90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films. Men who watch sexually explicit films also report increased motivation and competitiveness, and decreased exhaustion. A link has also been found between relaxation following sexual arousal and testosterone levels.
Androgens may modulate the physiology of vaginal tissue and contribute to female genital sexual arousal. Women's level of testosterone is higher when measured pre-intercourse versus pre-cuddling, as well as post-intercourse versus post-cuddling. There is a time lag effect when testosterone is administered, on genital arousal in women. In addition, a continuous increase in vaginal sexual arousal may result in higher genital sensations and sexual appetitive behaviors. Testosterone may prove to be an effective treatment in female sexual arousal disorders, and is available as a dermal patch. There is no FDA-approved androgen preparation for the treatment of androgen insufficiency; however, it has been used as an off-label use to treat low libido and sexual dysfunction in older women. Testosterone may be a treatment for postmenopausal women as long as they are effectively estrogenized.
The relationship between testosterone and romantic relationships is a complex and dynamic one. Falling in love has been linked with decreases in men's testosterone levels while mixed changes are reported for women's testosterone levels. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes. However, the testosterone changes observed do not seem to be maintained as relationships develop over time. Men who produce less testosterone are more likely to be in a relationship or married, and men who produce more testosterone are more likely to divorce. Marriage or commitment could cause a decrease in testosterone levels. Single men who have not had relationship experience have lower testosterone levels than single men with experience. It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts. Married men who engage in bond-maintenance activities such as spending the day with their spouse or child have no different testosterone levels compared to times when they do not engage in such activities. Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities is more relevant to changes in testosterone levels.
Men who produce more testosterone are more likely to engage in extramarital sex. Testosterone levels do not rely on physical presence of a partner; testosterone levels of men engaging in same-city and long-distance relationships are similar. Physical presence may be required for women who are in relationships for the testosterone-partner interaction, where same-city partnered women have lower testosterone levels than long-distance partnered women. The relationship between testosterone and romantic relationships is a complex and dynamic one, influenced by a variety of factors, including cultural norms, social expectations, and individual differences. The use of testosterone in the treatment of sexual dysfunction is a well-established application of the hormone, but the relationship between testosterone and romantic relationships is a complex and dynamic one, influenced by a variety of factors, including cultural norms, social expectations, and individual differences.