MUNICH — One year of hormone therapy for transgender conversion increases bone-mineral density both in men who convert to women and in women who convert to men. The most marked effect was seen in those who took estrogen for male-to-female conversion.

In female-to-male transgender patients, an increase in bone-mineral density was seen only in women who were postmenopausal at the time of conversion and whose estrogen levels were depleted; these patients were taking testosterone, explained Chantal Wiepjes, MD, from VU University Medical Centre, Amsterdam, the Netherlands, who was the principal investigator.

She presented the data at the European Congress of Endocrinology (ECE) 2016.

"Our data show that hormone treatment in transgender patients does not show any negative effects on the bones. It also clarifies the effects of testosterone on bone maintenance," said Dr Wiepjes, further explaining that "in female-to-male transgender patients [who received testosterone], an increase in bone density was only seen in postmenopausal women whose estrogen levels were depleted."

She explained that testosterone does not really have much effect on the bones per se, but it is converted into estradiol and it's the latter that accounts for the bone-strengthening effect seen in the women transitioning who are over 50 years of age.

"This confirms the notion that estrogen is the main regulator of bones," asserted Dr Wiepjes.

Prospective Study of Gender Incongruence

The prospective observational study was part of the European Network for Investigation of Gender Incongruence (ENIGI) and aimed to investigate the effects of cross-sex hormonal treatment on bone-mineral density during the first year of treatment in male-to-female and female-to-male transgender individuals.

A total of 306 participants (144 male-to-female, 162 female-to-male) underwent bone scans using dual-energy X-ray absorptiometry at baseline to measure lumbar spine and total hip bone-mineral density before treatment and again 1 year after.

Female-to-male conversions received intramuscular testosterone undecanoate (1000 mg/12 weeks), testosterone gel (50 mg/day), or testosterone esters intramuscular (250 mg/2 weeks). Male-to-female conversions were treated with cyproteronacetate (50 mg/day) in combination with oral estradiol valerate (2–4 mg/day) or an estradiol patch (200 µg/week). Blood samples were taken at baseline and 3 and 12 months to monitor levels of estradiol and testosterone.

The percentage change in mean bone-mineral density was recorded for each group, and results were stratified by age group (under 50 vs 50 years or more) and by use of vitamin D supplements. Adjustments were also made for changes in body weight.

Bone-Mineral Density Increase in Lumbar Spine, Not Hip

In male-to-female conversions, the mean change in bone-mass density over the year of treatment was most notable in the lumbar spine, at +3.8% compared with +1.0% in the hip. There was no difference seen by age group.

"Nearly all patients showed a mean increase in bone-mineral density," reported Dr Wiepjes. She added that the difference in results between the spine and the hip is most likely explained by the spine containing more trabecular bone; estrogen is thought to work specifically on trabecular bone.

In female-to-male conversions, when all ages were analyzed together, the mean change in bone-mineral density was +1.0% in the lumbar spine and +1.0% in the hip.

"When the results were stratified by premenopausal [under 50 years] and postmenopausal women [50 years or more] the lumbar spine mean bone-mineral density slightly increased to 0.8% in premenopausal women but rose to a 4.7% increase in the postmenopausal women," reported Dr Wiepjes.

These results indicate that the effects of testosterone are mainly due to its conversion into estradiol.

"If it had been an effect of testosterone we would have seen an effect in the premenopausal group, but we only saw a small increase in this group while we saw a big increase in the postmenopausal group," she explained.

When male-to-female results were stratified for vitamin D supplementation, patients taking supplements showed a larger increase in lumbar spine bone-mineral density (+5.2%), but the increase seen in those on estrogen alone was still +2.7%.

"Based on these results we cannot conclude that the findings are due to the vitamin D supplements," remarked Dr Wiepjes.

No difference was seen in the bone-mineral density of female-to-male patients whether they took vitamin D supplements or not.

"Our next steps will be to investigate what the long-term effects of hormone treatment are on bone density. Patients undergoing hormone therapy routinely have bone-density scans, which might give them the impression that hormone treatment can have adverse effects on their bones," continued Dr Wiepjes.

"For this reason, a more solid molecular long-term understanding of the changes may reassure them, I also think transitioning patients should be aware that the changes caused by these hormones aren't just external — their internal structure changes too."

Gunter Hofle, MD, from Landeskrankenhaus Hohenems Hospital, Austria, moderated the session and remarked that the patients who showed greatest benefit were the postmenopausal women who transitioned from female to male, because they are hypogonadal and effectively received hormone-replacement therapy, which is good for their bones.

"There was no disadvantage seen here."

He also highlighted important lifestyle information that these patients should heed. "It is important that these patients are advised not to smoke because smoking and hormone-replacement therapy gives an increased cardiovascular risk," including greater likelihood of an embolism, venous thrombosis, and/or myocardial infarction, he concluded.

Dr Wiepjes and Dr Hofle have declared no relevant financial relationships.

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European Congress of Endocrinology 2016; May 31, 2016; Munich, Germany. Abstract OC11.1