J Biol Regul Homeost Agents. Jan-Feb 2021; 35(1):5-10. doi: 10.23812/20-528-E.


Spontaneous miscarriages in patients with bladder pain syndrome/interstitial cystitis – effect of stress on inflammation?

Theoharides PC1,2,3, Christodoulou S2,4, Athanasiou A5.

Author information

1  Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, MA, USA.
2  Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA.
3  Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA.
4  Present address: Department of Surgery, Hygeia Hospital, Athens, Greece.
5  Department of Obstetrics and Gynecology, South Shore Hospital, South Weymouth, MA, USA.


Interstitial cystitis/painful bladder syndrome (IC/PBS) affects mostly women and is characterized by pelvic pain or pressure and frequency of voiding in the absence of urinary tract infection. Acute stress worsens IC/PBS symptoms and bladder inflammation associated with increased number of activated mast cells. We investigated retroactively the incidence of spontaneous miscarriages and any related stress in IC/PBS patients. A questionnaire was posted on an IC/PBS website and patients visiting the site were invited to complete and file it electronically. Limitations include the lack of defined diagnosis of those responding, and of a validated stress questionnaire. There were 193 respondents (mean age = 37.3 years) over two weeks. Of those responding, 87% (mean age = 33.2 years) had received a diagnosis of IC/PBS. Of those respondents with IC/PBS, 76% reported having had miscarriages: (a) 55% had one miscarriage, (b) 26% had two, and (c) 23% had three or more. These rates are much higher than those of in the general population: 10-20% with one and 1-2% with habitual spontaneous miscarriages. The majority of patients (78%) reported experiencing significant stress. IC/PBS patients appear to have a much high incidence of spontaneous miscarriages compared to the general population. Most patients reported experiencing stress that has been associated with miscarriages. This finding may be explained via stress stimulating bladder and uterine immune cells, especially mast cells, inhibition of which by the natural flavonoid luteolin may be beneficial.


corticotropin-releasing hormone, inflammation, mast cells, miscarriage, stress

Publication type

  • Editorial

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