Let’s Talk About Sex (Hormones)

The hypothalamic-pituitary-gonadal (HPG) axis, which is instrumental for puberty, is first activated much earlier in life during prenatal and postnatal development. This period is sometimes called minipuberty, and is important for testicular development in boys and maturation of ovarian follicles and increased estrogen in girls. It is thought that minipuberty lays the groundwork for pituitary LH and FSH responses to the GnRH hormone during the later reproductive phase of life.

There are a few reasons why some female children younger than 10 experience early puberty. One type of early puberty is caused by the pituitary gland making the hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which stimulate the ovaries to make estrogen. This can be caused by genetic defects or mutations, tumors, radiation, or trauma in the central nervous system. Early puberty can also be idiopathic, meaning there is no known cause.

Male children can also experience early puberty, although less frequently than in females. Early activation of the HPG axis results in excess testosterone. Some rare conditions, such as genetic malformations in the hypothalamic-pituitary region and certain types of tumors, can cause male children to make testosterone earlier than normal. Male (as well as female) children can also have too much testosterone if they are exposed to testosterone gel or other forms of testosterone that an adult male is using for treatment.

According to the Endocrine Society, a person’s internal sense of being a man, woman, neither, or both begins to develop in early childhood around age 2-4 years. A more developed sense of gender identity usually emerges in adolescence and may evolve over time.

There is no role for medications or surgeries in TGD children. Instead, the focus is on creating supportive spaces for the child to continue to explore their gender identity and assist with a social transition (use of chosen name, pronouns and gender expression) if desired. Psychosocial gender-affirming care during prepubescent years can help promote long-term well-being for TGD children through adolescence and beyond. 

Puberty is the stage when children and adolescents develop secondary sex characteristics and become sexually mature, typically occurring between ages 10 and 14 for female children and ages 12 and 16 for male children. The physical changes caused by puberty affect sexes differently. Both males and females may get acne and go through a growth spurt that lasts for about 2 or 3 years. This brings them closer to their adult height, which they reach after puberty.

In both sexes, estrogen is important for developing strong bones. In males, estrogen is also produced due to conversion from testosterone.

During puberty, estrogens and progesterone start to be secreted in quantity by cells in the ovary. Breast development is usually the first sign of puberty, followed by hair growth in the pubic area and armpits. Other changes include muscle growth and widening of the hips.

Menstruation typically follows. During each monthly menstrual cycle, estrogens stimulate the ovary to release an egg and thicken the uterine lining for possible pregnancy. Once ovulation occurs, estrogen decreases, and the uterine lining prepares to be shed during menstruation—beginning the cycle all over again.

The increased secretion of testosterone brings on the physical changes of male puberty, including penis and testes growth, facial, pubic, and body hair growth, deepening voice, muscle growth, and sperm production.

For TGD adolescents, going through puberty can be distressing, but can be prevented by giving puberty-blocking medications at the onset of the physical and hormonal changes of puberty. Temporarily using puberty blockers suppresses the body’s release of sex hormones, including testosterone and estrogen, which prevents the irreversible physical changes from puberty from occurring. This allows more time for the patient and their family to consider their options; most eventually choose to receive testosterone or estrogen to induce a puberty that matches their gender identity. A lower bone density has been seen in some groups of TGD adolescents who have received puberty-blocking medications but otherwise, these medications are reversible, and puberty will resume as normal if the medication is stopped.

During peak reproductive years when sex hormones are at their strongest, managing fertility becomes a priority, especially for females. While female hormonal contraceptives have been available since 1960, male hormonal and non-hormonal birth control options are still in the research phase. 

It can take several years for menstruation to become regular enough to be predictable. Because the menstrual cycle can be impacted by overall health status, it is sometimes regarded as a “fifth vital sign,” along with blood pressure, body temperature, heart rate, and respiratory rate.

Problems with menstrual cycles and estrogen secretion may cause PCOS, endometriosis, and other disorders, which can become more apparent to females in their 20s and 30s and can be diagnosed with careful clinical evaluation, hormone blood tests, and sometimes imaging.

Measuring Anti-Mullerian Hormone (AMH) levels can help determine a female’s remaining egg supply, although AMH testing is relatively new and has limitations. For most, AMH levels are at its highest during puberty and remain at a consistent level until menopause.

Testosterone levels are highest through ages 20 to 30. Testosterone levels change from hour to hour. They tend to be highest in the morning and lowest at night. For many reasons, testosterone can become—and stay—too low. Less often, testosterone levels can become too high. When this hormone is not in balance, health problems can sometimes result.

TGD adults may opt for medically necessary gender-affirming hormone therapy or surgery to achieve changes consistent with their embodiment goals, gender identity, or both. Medical interventions are provided with routine lab monitoring to achieve hormone levels comparable to those seen in cisgender people.

Because gender-affirming medical treatments often affect fertility, it’s important for TGD patients to understand any treatment implications for family-building.

At midlife, the most significant hormone shifts since puberty begin to occur. While females undergo a more dramatic reproductive hormone plunge during menopause, sex hormone changes in males occur gradually, and may not even be noticeable until after 60.

The average age for menopause onset is 51, but ovarian reserve (egg supply) begins to decline earlier, around 35. Most females become less fertile sometime in their mid-40s and may have difficulty conceiving after this age. During menopause, females naturally have lower levels of estradiol as the ovaries progressively decrease production, causing the menstrual cycles to become irregular and ultimately to stop. Declining estrogen levels can cause mood swings, vaginal dryness, hot flashes, and night sweats — the symptoms commonly associated with menopause. Hormone replacement therapy can help patients experiencing postmenopausal symptoms. The initiation of hormone replacement therapy needs to be carefully discussed with an experienced healthcare provider because it has specific contra-indications.  

Testosterone levels decline on average about 1% a year after age 40. But most males in this age range have testosterone levels within the normal range, with only an estimated 10% to 25% having levels considered to be low. Low testosterone often goes unnoticed. Though not routinely done, testosterone levels can be checked by a blood test.

TGD individuals taking hormone therapy at midlife may need to balance their hormone therapy with other needed medications and with the impact on co-existing medical conditions. Patients should receive screening for cancer as recommended for cisgender individuals, including organs that may have developed as a result of hormones (such as breast cancer screening in a transgender woman taking estrogen), or organs that are still present from birth (such as cervical cancer screening in a transgender man who has not had a hysterectomy.)

Aging is associated with a loss of sex hormone in both males and females. However, changes in multiple anabolic hormones—not just sex-specific hormones—can affect well-being in older age.

The postmenopause stage lasts for the rest of life. Decreasing sex hormones, such as estradiol, can increase osteoporosis and cardiovascular risk.

At age 70, the rate of testosterone decline increases to 2-3% per year. For some, this loss can trigger declines in bone and muscle mass and physical function.

Currently, there is no evidence to support terminating gender-affirming hormone therapy due to age. Ongoing research is examining the long-term benefits of continued treatment for older TGD adults. In most aging populations, there is concern about increased cardiovascular risk with any hormone therapy.

Levels of most hormones decrease with aging, but some hormones remain at levels typical of those in younger adults, and some even increase, like cortisol and insulin. Reproductive hormones that usually remain unchanged or only slightly decrease compared to early post-menopause include FSH and LH.

Estrone is the only estrogen the body continues to make in late menopause. Too much estrone has been linked to breast and endometrial cancer growth. Besides this potential outcome, other results of increased estrone levels are not yet known.

With counseling of benefits and risks and managed by an experienced health care provider, women can continue hormone replacement therapy beyond age 65 for persistent hot flashes, quality-of-life issues, or osteoporosis prevention.

Testosterone treatment of older males with symptomatic testosterone deficiency offers some clinical benefits. However, because of the lack of evidence of long-term safety and limited evidence of long-term efficacy, testosterone treatment is not justified for all older males and is offered on an individual basis depending on severity of symptoms.

Currently, there is no evidence to support terminating gender-affirming hormone therapy due to age. Ongoing research is examining the long-term benefits of continued treatment for older TGD adults. In most aging populations, there is concern about increased cardiovascular risk with any hormone therapy.