Androgen hormones may affect hypermobile EDS symptoms in women
Study: Gene changes in skin cells reveal altered hormone breakdown
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Women with hypermobile Ehlers–Danlos syndrome may process androgen hormones — steroid hormones such as testosterone and related male sex hormones — differently, which could be linked to some of their symptoms, according to a study.
More research is needed to understand why and whether it affects treatment, researchers wrote
The study, “Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition,” was published in the Journal of Steroid Biochemistry and Molecular Biology by researchers in the U.S.
“This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities [coexisting disorders],” they wrote.
Hypermobile EDS diagnosed more often in women
EDS comprises a group of diseases that affect the connective tissue, which supports and holds the body’s tissues together. Like in other types of EDS, joints are overly flexible and skin stretches more than usual in hypermobile EDS. It is diagnosed more often in women, and symptoms can change with hormonal shifts.
To understand whether hormones play a role in how severe symptoms are, the researchers compared 45 women with hypermobile EDS and 45 controls without the disease. Their ages ranged from 18 to 73 years. Blood samples were collected to measure steroid hormone metabolites, which are produced when the body produces or breaks down steroid hormones.
Compared with controls, women with hypermobile EDS had lower levels of several androgen sulfate metabolites. A sulfate metabolite is a hormone-related substance with a sulfate group attached, which can affect how the body transports, uses, or removes it. The differences were particularly common in women aged 30 to 49 years.
Sulfate metabolites included forms of androstanediol, androstenediol, androsterone sulfate, and epiandrosterone sulfate. These substances are involved in androgen metabolism, which refers to the chemical processes used to produce, modify, transport, and eliminate androgen hormones in the body.
89 of 95 genes has lower activity in women with hypermobile EDS
To investigate possible reasons for the lower levels of androgen metabolites, the researchers examined gene activity in skin fibroblasts, which are cells that help maintain connective tissue. Of 95 genes encoding proteins related to steroid hormones, 89 had lower activity and six had higher activity in fibroblasts from women with hypermobile EDS compared with controls.
For example, SRD5A2, which encodes an enzyme needed to produce precursors of androgen hormones, was about five times less active, and SULT2B1, which encodes an enzyme that adds sulfate groups to certain steroid hormones, was about 10 times less active in hypermobile EDS. SLCO1A2 and SLCO2B1, genes encoding proteins that help move sulfated androgens into cells, were also less active.
Levels of several androgen metabolites were associated with symptoms such as orthostatic intolerance (which may include dizziness on standing up) and problems with blood vessels and the bladder, particularly in women ages 18 to 29 years. Other steroid hormones were associated with pain, worse general health, and social limitations.
Overall, these data suggest that women with hypermobile EDS may process androgen hormones differently. The lower circulating levels could result from changes in hormone-producing or hormone-processing enzymes, sulfate attachment, or cellular transport.
“Given the significantly higher incidence and disease burden of [hypermobile EDS] in women, these novel data add interesting insights,” the researchers wrote.
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