6/08/2013

PMS: What is it anyway?



Prevalence

According to a 2009 review Premenstrual syndrome and premenstrual dysphoric disorder: quality of life and burden of illness. by Andrea J Rapkin, Sharon A Winer (Professor of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, USA), "Premenstrual symptoms are distressing for up to 20% of reproductive-aged women and are associated with impairment in interpersonal or workplace functioning for at least 3-8%. Typical symptoms of premenstrual syndrome and the severe form, premenstrual dysphoric disorder, include irritability, anger, mood swings, depression, tension/anxiety, abdominal bloating, breast pain and fatigue. The symptoms recur monthly and last for an average of 6 days per month for the majority of the reproductive years. For women with premenstrual dysphoric disorder, the symptoms can be as disabling as major depressive disorder. It has been estimated that affected women experience almost 3000 days of severe symptoms during the reproductive years. Until two decades ago, there were no effective treatments for severe premenstrual syndrome. Even in 2000, almost three-quarters of women in the USA with premenstrual disorders either did not seek help or sought treatment unsuccessfully from at least three clinicians for over 5 years"
According to a 2007 review Premenstrual syndrome. by Irene Kwan, Joseph Loze Onwude (Royal College of obstetricians and gynaecologists, London, UK.), "Premenstrual symptoms occur in 95% of women of reproductive age. Severe, debilitating symptoms (PMS) occur in about 5% of those women. There is no consensus on how symptom severity should be assessed, which has led to a wide variety of symptoms scales, making it difficult to synthesise data on treatment efficacy." With that excuse, these physicians did not show much interest in getting to the root cause, but seem to think they can somehow come to some conclusion on treatment efficacy based on highly biased set of data, without knowing the root cause. 

Let me assure you that I am not at all interested in that kind of approach, and will follow the trails of research that are designed to uncover the root cause. Thank goodness they exist!


What's to be included?

In the course of this research, I found 4 areas of studies that deal with problems associated with  menstrual cycle.
1.   Irritable bowel syndrome (mainly constipation before and increased bowel movements shortly before or at the onset of menses, may be cramping during the heavy flow)
*For men, the majority of Irritable bowel syndrome (IBS) is diarrhea as the name suggest, and I am not sure about the wisdom of putting women's constipation related problems in the same category.

2.   PMS: Physical symptoms such as breast tenderness and swelling, weight gain, headache, abdominal cramping and bloating, food cravings, thirst, nausea, joint pain, acne, dizziness, hyperalgesia (increased pain sensitivity) and one or more psychological symptoms such as irritability, lethargy and fatigue, depression, anxiety, hostility and aggression

3.   PMDD (Premenstrual Dysphoric Disorder, severe form of PMS)

4.   Catamenial Epilepsy (Epilepsy worsening during premenstrual days): A twofold increase in average daily frequency during the phase of exacerbation relative to other phases defines catamenial epilepsy for research purposes (Hormones and Epilepsy. Mira Katan, Epileptologie 2011; 28).



Relation to menstrual cycle: Catamenial Epilepcy


Since Catamenial Epilepsy has the most clear cut and unmistakable definition of the symptoms, let's look at its relation to the menstrual cycle. The following figure from Three patterns of catamenial epilepsy. A G Herzog, P Klein, B J Ransil, (1997) shows two phases (C1 and C2) for a normal cycle and one phase (C3) for disturbed (no progesterone) cycle, all of which are the high estrogen and low progesterone phases.


 Three patterns of catamenial epilepsy. A G Herzog, P Klein, B J Ransil, (1997) 

 
In terms of the actual seizure occurrences, as shown in the following figures, C1 (from 3 days before to 3 days after the start of menses) is the primary phase for the Catamenial Epilepsy to occur, followed by days surrounding ovulation (days 10 to -13) during normal cycles. On the other hand, during anovulatory (no progesterone) cycles, lower average daily frequency is seen only during the Follicular phase (days 4 to 9). As women approach menopause, this C3 pattern cycle increases.

 
 Three patterns of catamenial epilepsy. A G Herzog, P Klein, B J Ransil, (1997) 


This shift in the pattern of estradiol/progesterone ratio can be also seen in post-partum and [Epilepsy and pregnancy]. I E Poverennova, A V Iakunina, E N Postnova, V A Kalinin, I S Kordonskaia, L E Chueva 2008 reported "It was shown that, along with the last weeks of pregnancy, the first 7 days period after the delivery was critical for epilepsy severity. The development of seizures at this period was related to sleep deprivation and marked hormonal changes."


Relation to menstrual cycle: PMS

When you look at self reported PMS symptom severity scores for normal cycles (reported by Symptom patterns in women with premenstrual syndrome complaints: a prospective assessment using a marker for ovulation and screening criteria for adequate ovarian function. H Sveinsdottir, N Reame 1991), you can see patterns similar to the above Catamenial Epilepsy patterns. That is, as you can see from the following graphs, women are feeling well during the days leading up to ovulation (before LH Surge days), and bothered by some PMS related symptoms during the days leading up to the start of menses and a few days into it (days 25 ~ 3, of which 0~3 =heavy flow days). There are individual differences in the duration and the severity. Some start to have problems right before ovulation when estrogen surges.
   



Apparently, it is common to feel rotten during the week leading up to menstruation, and the first few days of menses, even if it is not debilitating or disruptive according to some survey (Patterns of mood changes throughout the reproductive cycle in healthy women without premenstrual dysphoric disorders. X Gonda, T Telek, G Juhász, J Lazary, A Vargha, G Bagdy 2008). Actually, Premenstrual dysphoria, the severe form of PMS has shown a significant relationship to epilepsy, and its symptoms correspond to those of the interictal (between seizures) dysphoric disorder (To what extent do premenstrualand interictal dysphoric disorder overlap? Significance for therapy. D Blumer, A G Herzog, J Himmelhoch, C A Salgueiro, F W Ling 1998)

Relation to menstrual cycle:  Irritable bowel syndrome


Also the pattern of premenstrual constipation followed by frequent bowel movements with normal or loose stools shortly before or at the onset of menses has been studied as irritable bowel syndrome rather than PMS, and very common according to Meta-analysis: do irritable bowel syndrome symptoms vary between men and women? (M A Adeyemo, B M R Spiegel, L Chang, 2010). That certainly was my personal experience, too.
Unfortunately, I could not find any data that shows pattern of IBS in relation to menstrual cycle or estrogen-progesterone ratio. So, I have to go by my own case. I experienced two types: before surgical menopause at 45, and after with estrogen only HRT. Before menopause, the problem was constipation that progressively worsened until 2 days before the onset of menses, at which time constipation abruptly ended. Interestingly, it was accompanied by one time release of some flagrant substance detectable in urine. Progesterone often is blamed for constipation as well as PMS, however, the simple fact that it progressively worsened rather than peaked at the mid luteal when the progesterone is highest does not support that argument. After menopause with estrogen only HRT, in extreme estrogen dominant state, constipation and diarrhea alternated. It was clear to me that diarrhea was triggered by stress and fatigue. This problem was resolved when I added progesterone (in cream form) to my HRT. At the time, diarrhea was dominating, and the addition of progesterone put an end to it almost instantly without bringing back constipation. It's been about 15 years since, constipation still is a problem if I don't keep up with water and magnesium intake.
Judging from the timing, PMS completely overlaps with constipation in normal cycle, and diarrhea with estrogen dominance (no progesterone) cycle, at least in my case. All the psychological traits assciated with PMS - anxiety, interpersonal sensitivity, depression, hostility, and somatization of affect were observed in IBS patients (Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients. W E Whitehead, B T Engel, M M Schuster 1980; Coping strategies, illness perception, anxiety and depression of patients with idiopathic constipation: a population-based study. C Cheng, A O O Chan, W M Hui, S K Lam 2003; Are anxiety and depression related to gastrointestinal symptoms in the general population? T Tangen Haug, A Mykletun, A A Dahl 2002; Psychological state and quality of life in patients having behavioral treatment (biofeedback) for intractable constipation. Heather J Mason, Esther Serrano-Ikkos, Michael A Kamm 2002), although, depression of PMS or IBS patients detected by a simple questionnaire test turned out to be nothing like that of major depression in terms of cognitive functioning (Mood and cognitive style in premenstrual syndrome. A J Rapkin, L C Chang, A E Reading 1989) and neuro-hormonal stress response functioning (Differential menstrual cycle regulation of hypothalamic-pituitary-adrenal axis in women with premenstrual syndrome and controls. Catherine A Roca, Peter J Schmidt, Margaret Altemus, Patricia Deuster, Merry A Danaceau, Karen Putnam, David R Rubinow 2008).

Anybody who experienced constipation knows how uncomfortable it is physically. It sometime causes dull head feeling or even headaches. You cannot maintain a good mood when it happens. Biologically, toxins meant to be expelled may be reabsorbed, or gut microbes my generate more toxic substances the longer the food stays inside. Also certain nutrients such as magnesium may be depleted by excess gut microbes activities. On the other hand, repeated diarrhea can deplete electrolyte (minerals) for sure. Yet, constipation and diarrhea is not taken seriously as a cause of various physical and psychological problems. Luckily, however, they can be easily resolve in most cases by magnesium laxatives for constipation and progesterone cream for diarrhea. Why? See the underlying mechanism section.