Hormonal and Endocrine Issues in hEDS

Hypermobile Ehlers-Danlos syndrome (hEDS) is primarily known for joint hypermobility, pain, and connective tissue fragility. However, many individuals also report symptoms that resemble hormonal or endocrine problems, such as fatigue, menstrual changes, and sensitivity to hormonal fluctuations. This has led to questions about whether hEDS affects the endocrine system—the network of glands that produce hormones controlling everything from metabolism to reproduction.

Current research shows that most endocrine symptoms in hEDS—particularly in women—are related to the reproductive system. There is no increased risk of thyroid or adrenal gland diseases in hEDS, though these glands should still be considered in the differential diagnosis when symptoms like fatigue occur. This article provides a comprehensive overview of hormonal issues in hEDS across all age groups and sexes, explaining what is supported by scientific evidence and what remains theoretical or unproven.

Summary of Findings

• Most common endocrine-related symptoms occur in the female reproductive system (e.g., heavy or painful periods).

• No increased risk of thyroid or adrenal disease in hEDS across any age group.

• Fatigue and dizziness, often confused with hormone disorders, are usually due to autonomic dysfunction or comorbid conditions like POTS or mast cell activation.

• Evaluation for hormonal problems should be based on symptoms—not done routinely without cause.

• Standard treatments are effective and generally appropriate; no hEDS-specific endocrine treatments are needed.

Gynecologic and Reproductive Hormone Issues

These are the most common endocrine-related complaints in people with hEDS, especially in adolescent and adult females. (Also see separate Information page on Women's Health.)

Management Strategies

• First-line hormonal treatment: Progesterone-only birth control pills

• Second-line options:

  • Injectable birth control (DMPA)

  • Hormonal intrauterine devices (IUDs)

• Other treatments:

  • Antifibrinolytics for bleeding

  • Pelvic floor physical therapy for pain

Referral to a gynecologist with EDS experience is recommended for adolescents and adults with significant symptoms.

Endocrine Glands Not Affected by hEDS

Despite overlapping symptoms, there is no evidence that hEDS directly affects the thyroid, adrenal glands, or pituitary system.

• Thyroid Gland

  • Function: Regulates metabolism, energy, temperature

  • Common conditions: Hypothyroidism (underactive thyroid), hyperthyroidism (overactive)

  • In hEDS: No increased rates of thyroid disease

  • Important to note: Fatigue, weight changes, or cold intolerance may prompt thyroid testing, but results are usually normal unless a separate thyroid disease is present.

• Adrenal Glands

  • Function: Produce stress hormones (like cortisol), salt-balancing hormones, and sex hormone precursors

  • Common conditions: Addison’s disease (adrenal insufficiency), Cushing’s syndrome (cortisol excess)

  • In hEDS: No increased prevalence of adrenal dysfunction

  • Exception: A rare condition called CAH-X syndrome includes both adrenal insufficiency and EDS features but is genetically distinct from hEDS.

When to Test

If a person with hEDS has

• Unexplained fatigue

• Blood pressure issues (dizziness, fainting), and/or

• Extreme stress intolerance

then testing for thyroid and adrenal disorders is appropriate—but not routinely recommended without symptoms.

Commonly Confused Conditions

People with hEDS often experience symptoms that mimic endocrine disorders but have other causes.

Role of Autonomic Dysfunction and Mast Cells

• Autonomic Dysfunction (Dysautonomia)

  • Common in hEDS (especially postural orthostatic tachycardia syndrome or POTS)

  • Affects how the nervous system controls blood pressure, heart rate, digestion, and temperature

  • Can influence hormone regulation indirectly

  • Treatment: Increased fluids/salt, compression garments, exercise, medications like fludrocortisone or midodrine

• Mast Cell Activation Syndrome (MCAS)

  • Overactivity of mast cells can cause inflammation and symptoms throughout the body

  • May worsen hormone-related symptoms, including gynecologic pain and bladder irritation

  • Treatment: Antihistamines, mast cell stabilizers, trigger avoidance

Differences Across Age and Sex

• Children and Adolescents

  • Main issues: heavy or painful periods in females, sometimes starting soon after puberty

  • Hormonal fluctuations may worsen hEDS symptoms

  • No evidence of thyroid or adrenal disease being more common

• Adults

  • High rates of reproductive hormone sensitivity, including worsened hEDS symptoms during

    • Puberty

    • Menstrual cycles

    • Postpartum

    • Hormonal birth control use

  • Increased risk of miscarriage and pelvic pain

• Geriatric Populations

  • Very limited data

  • Symptoms like pain and stiffness dominate

  • Standard screening for age-related endocrine conditions (e.g., osteoporosis, thyroid dysfunction) still applies

• Males with hEDS

  • No increased rates of endocrine disorders

  • Reproductive or urinary symptoms (e.g., erectile dysfunction, bladder issues) may occur but are likely due to connective tissue laxity, not hormone imbalance

    
    

Clinical Recommendations

What’s Still Unknown

Despite increased awareness, important questions remain

• How do hormone fluctuations affect joint stability and pain in hEDS?

• Do hormonal treatments for menstrual symptoms affect long-term outcomes in hEDS?

• What are the best ways to differentiate between endocrine, autonomic, and inflammatory symptoms?

• How does aging affect hormone balance in people with hEDS?

Currently, there are no clinical trials or disease-specific treatment studies focused on hormonal or endocrine issues in hEDS.

Summary

Hormonal and endocrine symptoms are common in people with hEDS, but the majority of concerns involve the reproductive system—especially in females. There is no evidence that hEDS causes thyroid, adrenal, or pituitary gland problems more often than in the general population. Still, testing for these conditions may be appropriate when symptoms suggest them. Fatigue, dizziness, menstrual issues, and heat or cold sensitivity in hEDS are more likely to stem from autonomic dysfunction, connective tissue problems, or comorbid conditions like POTS or MCAS.

Treatment is symptom-focused, using standard medical protocols, and should involve gynecologists, endocrinologists, and primary care providers working together when necessary. Future research is needed to better understand hormonal sensitivity in hEDS and to improve care for patients across all ages.