Ehlers-Danlos Syndromes and Heavy, Painful Periods

Ehlers-Danlos Syndromes and Heavy, Painful Periods

Why it’s Linked to High Rates of Gynaecological Issues

Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders characterised by joint hypermobility, skin hyperextensibility, and tissue fragility. There are 13 distinct subtypes — twelve of which are caused by mutations in collagen or collagen-processing genes, such as classical EDS and vascular EDS. The exception is hypermobile EDS (hEDS): by far the most common subtype, and the only one not yet linked to an identified gene. Diagnosis therefore relies entirely on clinical criteria rather than a genetic test.

EDS is most often discussed in the context of joints and chronic pain — but its effects on menstrual and gynaecological health are profound, and significantly underrecognised.

EDS and Worse Periods

Studies confirm what many people with EDS already know: periods can be brutal. In research on classical and hypermobile EDS (1-5).

• 90% experience period pain
• 80% experience heavy bleeding
• 31% bleed between periods

In vascular EDS, the picture is even more severe - over half experience heavy bleeding lasting more than 7 days, alongside higher rates of bleeding between periods (1).

So how does a connective tissue disorder affect periods?

Collagen isn't just in your joints and skin - it's a structural component of blood vessels, smooth muscle tissue, and the uterine wall itself. When collagen is dysfunctional:

• Blood vessels in the uterine lining become fragile and poorly contractile. Normally, these vessels constrict to limit blood flow during menstruation. In EDS, this may be impaired - contributing to heavier, more prolonged bleeding and spotting between periods (6).
• Uterine movement and contraction become dysregulated. EDS is associated with uterine retroversion (a tilted uterus) and abnormal smooth muscle function. During menstruation, the uterus may distend excessively and move more than it should, producing uncoordinated, prolonged contractions - and therefore more painful period cramps.
  
  

EDS and Endometriosis

A large study found that if you have endometriosis, you’re 7x more likely to also have Ehlers-Danlos (7).

The mechanism isn't yet fully understood. One hypothesis is that the abnormal extracellular matrix (the structural scaffolding surrounding cells) in EDS may make it easier for endometrial-like cells to migrate and proliferate.

Associated Gynaecological Conditions

Compared to those without EDS, research shows you are significantly more likely to have a range of conditions that involve gynaecological aspects (8-9):

→ Vulvodynia: affects ~50% with ED
Likely driven by a combination of pelvic floor dysfunction, the strong association between EDS and neuropathic pain mechanisms, and mast cell activation. In vulvodynia, mast cells have been found to accumulate in vulvar tissue and are thought to contribute to localised hypersensitivity and pain.

→ Dyspareunia (painful intercourse): 4x more likely (affects ~64% with EDS)
Pelvic floor dysfunction, tissue fragility, and vulvodynia may all contribute - this figure reflects just how overlapping and compounding these conditions can be.

→ Chronic pelvic pain: 3x more likely
Collagen dysfunction leads to instability in pelvic ligaments, muscles, and supporting tissues, increasing the likelihood of micro-tears, inflammation, and ongoing pain.

→ Pelvic organ prolapse: 7-9x more likely
When the collagen scaffolding of the pelvic floor is structurally compromised, the muscles and ligaments that support the bladder, uterus, and bowel can no longer do their job effectively - making prolapse far more likely, and often at a younger age than in the general population.

→ Urinary incontinence: 6x more likely
In EDS, the collagen supporting the urethral sphincter and surrounding tissue is lax, meaning it takes less pressure to overcome - so coughing, sneezing, laughing, or exercise can trigger leakage. Pelvic floor muscles also have to overwork to compensate for ligament laxity, which can paradoxically lead to both weakness and hypertonicity (an overly tight, dysfunctional floor) - the latter associated with urgency incontinence, where the urge to urinate is sudden and difficult to control.

How do Hormones affect EDS?

Over 1 in 3 with EDS notice their symptoms (pain, fatigue, joint instability) get WORSE just before/during their period (10).

Estrogen receptors are found throughout joints, tendons, skin, and cartilage. The relationship is complex but estrogen can indeed influence connective tissue. Crucially, estrogen also activates mast cells - which are found throughout connective tissue. Mast cell activation syndrome (MCAS) has a striking comorbidity with hEDS, and dysfunctional connective tissue may further disrupt their normal regulation. When triggered, mast cells release histamine, prostaglandins, and other inflammatory mediators - contributing to pain, bloating, fatigue, brain fog, and skin reactivity, many of which track closely with hormonal shifts across the menstrual cycle.

Relaxin is particularly relevant. Produced during the luteal phase and in much higher concentrations during pregnancy, it directly increases ligament extensibility - a useful adaptation in a healthy connective tissue system, but potentially destabilising in someone whose ligaments are already lax.

Progesterone's role remains the least studied, which is a significant gap given how it shifts across the cycle and how commonly people with EDS report symptom changes in the luteal phase.

Another important aspect is the strong female dominance in EDS prevalence, with a ratio of 2:1 and sometimes as high as 9:1 (10,11). This divergence between the sexes seems to emerge at adolescence, as in childhood the rates of EDS in men and women are much similar, suggesting a strong hormonal influence to the etiopathogenesis of the condition. 

Going Through Puberty with EDS

Many with EDS have their symptom onset at puberty. In a cohort of 386 women with hypermobile EDS, 52% reported that their symptoms began or worsened at puberty (10). This may result either from the rapid growth that is characteristic of this time in life that significantly affects skin, joints and muscles, and/or the increase in estrogen secretion.

The Takeaway 

EDS is too often framed as just a joint condition - something that affects flexibility and causes dislocations. But the evidence is clear that it is systemic, with far-reaching effects on vascular integrity, immune regulation, and organ support. The menstrual and gynaecological burden it carries is not incidental - it is mechanistically rooted in the same collagen dysfunction that affects every other system in the body. If you have EDS and have been told your heavy periods, pelvic pain, or gynaecological symptoms are unrelated, or have been dismissed without investigation, that dismissal was not based on the science. These experiences are connected, they are real, and they deserve to be taken seriously.

We need more research to provide answers, and solutions to follow.  

References: 

1. Hurst et al. Obstetric and gynecologic challenges in women with Ehlers-Danlos syndrome. Obstet Gynecol. 2014

2. Hurst BS, Lang MB, Kullstam SM, Usadi RS, Matthews ML, Marshburn PB. Reproductive challenges in women with ehlers-danlos syndrome: survey results from over 1350 respondents from the ehlers-danlos national foundation. Fertil Steril. (2012)

3. Hernandez & Dietrich. Gynecologic Management of Pediatric and Adolescent Patients with Ehlers-Danlos Syndrome. J Pediatr Adolesc Gynecol. 2020.

4. Castori et al. Gynecologic and obstetric implications of the joint hypermobility syndrome (a.k.a. Ehlers-Danlos syndrome hypermobility type) in 82 Italian patients. Am J Med Genet A. 2012

5. Wright, Tonya S.; Cygan, Peter H.; . Closing the Diagnostic Gap in Adolescents and Young Adult Women With Bleeding Disorders: Missed Opportunities. Obstetrics & Gynecology. 2023.

6. Malfait & De Paepe. Bleeding in the heritable connective tissue disorders: mechanisms, diagnosis and treatment. Blood Rev. 2009

7. Khan et al. Comorbidity analysis and clustering of endometriosis patients using electronic health records. Cell Rep Med. 2025

8. Glayzer JE, McFarlin BL, Castori M, Suarez ML, Meinel MC, Kobak WH, et al. High rate of dyspareunia and probable vulvodynia in ehlers-danlos syndromes and hypermobility spectrum disorders: an online survey. Am J Med Genet C Semin Med Genet. (2021) 187:599–608. 10.1002/ajmg.c.31939

9. Imbroane MR, Kim H, Akesson C, Richards EG. Assessing the Risk of Gynecologic and Obstetric Diagnoses in Patients with Ehlers-Danlos Syndromes. J Womens Health (Larchmt). 2026

10. Hugon-Rodin et al. Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study. Orphanet journal of rare diseases. 2016

11. Wu & Ho. An overview of Ehlers Danlos syndrome and the link between postural orthostatic tachycardia syndrome and gastrointestinal symptoms with a focus on gastroparesis. Frontiers in neurology. 2024
    

Additional reading

Pollack et al. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Front Rehabil Sci. 2023