Histamine Intolerance & PCOS: What's the Link?

This is a quick list of the relationship between histamine intolerance and polycystic ovarian syndrome (PCOS).

There is a strong histamine-PCOS connection^1–3
Oestrogen dominance plays a key role in PCOS, premenstrual syndrome (PMS), uterine fibroids and breast cancer
Those with PCOS tend to have low progesterone levels^4,5
Progesterone is required for the enzyme, diamine oxidase (DAO), that breaks down histamine in the digestive tract and body^6,7
There is a DAO gene, so a deficiency of DAO can be due to a genetic mutation^8,9
Without sufficient progesterone, DAO enzyme function is impaired, resulting in excess histamine^6,7
Oestrogen causes histamine production and release from ovaries and uterus^6,7
Histamine causes oestrogen production, resulting in a loop^6,7
Oestrogen dominance may exacerbate PMS symptoms^10,11

References^12,13

1.
Erol N. Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome. WJC. Published online 2014:1285. doi:10.4330/wjc.v6.i12.1285
2.
Krishna A, Beesley K, Terranova PF. Histamine, mast cells and ovarian function. Journal of Endocrinology. Published online March 1989:363-371. doi:10.1677/joe.0.1200363
3.
Azziz R. Polycystic Ovary Syndrome. Obstetrics & Gynecology. Published online August 2018:321-336. doi:10.1097/aog.0000000000002698
4.
Velija-Ašimi Z. Evaluation of endocrine changes in women with the polycystic ovary syndrome during metformin treatment. Bosn J of Basic Med Sci. Published online August 20, 2013:180. doi:10.17305/bjbms.2013.2359
5.
Yang Y, Liu B, Wu G, Yang J. Exploration of the value of progesterone and progesterone/estradiol ratio on the hCG trigger day in predicting pregnancy outcomes of PCOS patients undergoing IVF/ICSI: a retrospective cohort study. Reprod Biol Endocrinol. Published online December 2021. doi:10.1186/s12958-021-00862-6
6.
Fogel WA. Diamine oxidase (DAO) and female sex hormones. Agents and Actions. Published online April 1986:44-45. doi:10.1007/bf01987978
7.
Hamada Y, Shinohara Y, Yano M, et al. Effect of the menstrual cycle on serum diamine oxidase levels in healthy women. Clinical Biochemistry. Published online January 2013:99-102. doi:10.1016/j.clinbiochem.2012.10.013
8.
Okutan G, Ruiz Casares E, Perucho Alcalde T, et al. Prevalence of Genetic Diamine Oxidase (DAO) Deficiency in Female Patients with Fibromyalgia in Spain. Biomedicines. Published online February 22, 2023:660. doi:10.3390/biomedicines11030660
9.
Agúndez JAG, Ayuso P, Cornejo-García JA, et al. The Diamine Oxidase Gene Is Associated with Hypersensitivity Response to Non-Steroidal Anti-Inflammatory Drugs. Ryffel B, ed. PLoS ONE. Published online November 12, 2012:e47571. doi:10.1371/journal.pone.0047571
10.
Yen, Lin, Lin, Liu, Long, Ko. Early- and Late-Luteal-Phase Estrogen and Progesterone Levels of Women with Premenstrual Dysphoric Disorder. IJERPH. Published online November 7, 2019:4352. doi:10.3390/ijerph16224352
11.
Noviyanti NI, Gusriani, Ruqaiyah, Mappaware NA, Ahmad M. The effect of estrogen hormone on premenstrual syndrome (PMS) occurrences in teenage girls at Pesantren Darul Arqam Makassar. Gaceta Sanitaria. Published online 2021:S571-S575. doi:10.1016/j.gaceta.2021.10.103
12.
Arduc A, Aycicek D, Bilmez S, et al. High prevalence of Hashimoto’s thyroiditis in patients with polycystic ovary syndrome: does the imbalance between estradiol and progesterone play a role? Endocr Res. 2015;40(4):204-210. doi:10.3109/07435800.2015.1015730
13.
Maintz L, Novak N. Histamine and histamine intolerance. The American Journal of Clinical Nutrition. Published online May 2007:1185-1196. doi:10.1093/ajcn/85.5.1185