PMS, Bloating, PCOS, OHSS, ART, and …

If you know what PCOS and OHSS mean, you probably have been through ART. For those who are not familiar with these acronyms, PCOS is short for Polycystic Ovary Syndrome and OHSS is short for Ovarian Hyper Stimulation Syndrome, which goes hand in hand with PCOS in Assisted Reproductive Treatments (ART).

I don't mean to ridicule those who went through the ordeal, but both PCOS and OHSS are preventable and if you sought ART due to PCOS and ended up with OHSS, you did not get the best medical advice or treatments. Supplementation of real (bio-identical to human's) progesterone is known to prevent OHSS and it is part of the established guideline for prevention of OHSS (e.g. THE MANAGEMENT OF OVARIAN HYPERSTIMULATION SYNDROME by Royal College of Obstetricians and Gynaecologists, 2006).

In case you don't know what Ovarian Hyper Stimulation Syndrome is, it is a rare but potentially fatal complications that occurs when ovulation is induced by administering high doses of follicular stimulating hormone (FSH extracted from human urine or produced by recombinant technology) in combination with some other ovulation controling hormones. Its prominent feature is enlarged ovaries with multiple mature follicles producing extremely high level of estrogen. After ovulation, bloating develops with fluid rapidly accumulating in abdominal cavities, eventually spreading to other organs including lungs, while blood gets thicker and the resulting blood clots and organ failures can lead to fatality, if acute respiratory distress syndrome or diarrhea with electrolyte imbalance did not.

The significance of OHSS research in understanding PMS and pre-menopausal symptoms lies in the fact that it deals with the exact same hormonal pattern, only amplified many times over. Moreover, since it is dealing with life and death conditions, one can hope that any misconceptions and misinformation such as "progesterone causes edema" or "there is no difference between various progesterone like drugs and real progesterone" will be exposed and expelled. One might also argue that the misguided attribution of edema to progesterone delayed the identification of the real cause and effective treatment. Ujioka et al. 1997 is one such misguided study.

The most elegant and decisive study I came across is Louis Chukwuemeka Ajonuma, et. al. 2005. They have observed clear indications that estrogen promotes fluid shift and progesterone suppresses it. They also demonstrated the underlying mechanism mediated by cystic fibrosis transmembrane conductance regulator (CFTR), which is up-regulated by estrogen and down-regulated by progesterone. The reason it is called cystic fibrosis transmembrane conductance regulator is that certain mutation of CFTR is known to cause cystic fibrosis. The critcal involvement of CFTR was demonstrated by showing that OHSS does not occur in animals with such CFTR mutations, neither in normal animals with CFTR expression blocked.

CFTR is also known for its role in several pathological conditions, such as cholera-induced diarrhea, in which there are massive fluid fluxes across epithelial membranes.

Now, going back to PMS and peri-menopausal symptoms, in which the high level of follicular stimulating hormone (FSH) induces enlarged ovaries and high level of estrogen WITHOUT corresponding high level of progesterone, it perfectly makes sense that bloating or edema is one of the main symptoms, and supplementation of real progesterone alleviate the symptoms. Actually, the effect of progesterone in reducing edema is so strong that it has been demonstrated to save brain injured patients if it is started within 6 hours (ideally within 2 hours) of the injury by a team of Emory Univerciy researchers.

Also the large individual differences in the manifestation of bloating in PMS and peri-menopausal symptoms is understandable, since CFTR has many variations (more than 1000 identified).

When we talk about PMS and peri-menopausal symptoms, we cannot avoid talking about all those negative mood swings, which is almost synonymous with PMS. In OHSS studies, they are too busy trying to save the mother and the pregnancy, everything else seems to take a backseat. So we have to look elsewhere for hormone related mood swings and their underlying mechanism. Here is the first of 3 part series. In the course of this research, I found 4 areas of studies that deal with problems associated with menstrual cycle: Irritable bowel syndrome, PMS, Premenstrual Dysphoric Disorder, and Catamenial Epilepsy. Because menopause has been my main concern, I have not looked into this topic very closely until now, and Wow! The best research was done in 1990's. As far as I can tell, they knew everything we need to know to formulate effective remedies back then. Did you know? 

By the way, if you are interested in clinical (human) OHSS studies, a review by Abbas Aflatoonian, M.D., Tahereh K. Bidgoli, M.D. Prevention is the ideal treatment of OHSS!!! 2005 is a good place to start.

References

Royal College of Obstetricians and Gynaecologists. THE MANAGEMENT OF OVARIAN HYPERSTIMULATION SYNDROME. Green-top Guideline No. 5, September 2006

Takeshi Ujioka, Kohei Matsuura, Tetsuro Kawano, and Hitoshi Okamura. Role of progesterone in capillary permeability in hyperstimulated rats. Human Reproduction vol.12 no.8 pp.1629?1634, 1997

Louis Chukwuemeka Ajonuma, Lai Ling Tsang, Gui Hong Zhang, Connie Hau Yan Wong, Miu Ching Lau, Lok Sze Ho, Dewi Kenneth Rowlands, Chen Xi Zhou, Chuen Pei Ng, Jie Chen, Peng Hui Xu, Jin Xia Zhu, Yiu Wa Chung, and Hsiao Chang Chan. Estrogen-Induced Abnormally High Cystic Fibrosis Transmembrane Conductance Regulator Expression Results in Ovarian Hyperstimulation Syndrome. Molecular Endocrinology 19(12):3038–3044

David W. Wright et al. ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury. Ann Emerg Med. 2007;49:391-402

Abbas Aflatoonian, M.D., Tahereh K. Bidgoli, M.D. Prevention is the ideal treatment of OHSS!!! Iranian Journal of Reproductive Medicine Vol.3. No.2 pp:51-61, 2005