THE CASE HISTORY OF A 32-YEARS-OLD WOMAN WITH PREMENSTRUAL SYNDROME BY NOW REBELLIOUS TO USUAL THERAPIES, IMPROVED WITH ANTISTRESS DRUGS (Final updating)

Renato COCCHI, neurologist and medical psychologist.

 

(Italian translation)

 

  Summary.

A woman 32 years old at first consultation, with an imposing premenstrual syndrome, by now rebellious to the  hormonal treatment lasted 15 years, and to the psychotherapeutic treatment, was treated with antistress drugs. Since the first following cycle she showed a massive reduction  of either her psychic and somatic symptoms, and the same for the three following menses. This is the detailed report of theset 39 months therapy.  

Key words; Premestrual syndrome, stress, drugs, antistress therapy.

 

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  In 1998, during the 2° World Congress on Stress, in Melbourne, I read a free communication on the pre-menstrual syndrome as paradigm of an internal metabolic stress.

Some time later I inserted this communication in my Internet site, putting it into the field named Speculations, since I did not had got yet any satisfying clinical case history about what I sustained  and I am sustaining it.

So I wrote there: "The premenstrual syndrome (PMS) is the most evident example of stress of internal metabolic origin. It has the striking feature of coming out from a physiological process of the fertile woman. The cut down of the level of progesterone (the late luteal phase of the menstrual cycle) does influence the homeostasis, inducing stress reactions. Those use final common pathways and produce nonspecific symptoms (excluding perhaps breast tenderness, bloating and swelling)."

Now, I am convinced that neither the last  three are specific symptoms. Only recently, however, it occurred I could  verify in my clinical practice what I had realized.

I treated a PMS, till now rebellious to the usual therapies (Douglas, 2002), with antistress drugs, since the symptoms of stress were evident.  As it follows, I shall give its wider report out, which has even the clinical subjective history written by the patient, and here published with her consent.  

 

The case history.  

07.09.2002: She is nearly 32 years at the first consultation and complains for a PMS with depression, anxiety, retchs, colic pain and of the kidney areas, weeping, desperation sense, irritability towards the objects and the persons, not more mammary tension after stopping of the oestrogenic-progestinic pill, some  sleep troubles, abdominal swelling, headache, foods' refusal (Cross et al, 2001), a lump in the throat,  unwillingness, faint feelings, not stomachache, tiredness, bad thoughts, not intrusive thinking, light early-morning fatigue.

When working, she improves her discomfort.  In the premenstrual days her hairs become more fat, and they do not hold the set. She reports also hand and armpit oversweating, and tachycardia not limited premenstrual period. Dreams of family mourning occur. When sleeping she is not slobbering,  and do not have cramps. She stands badly noise and people confusion, does not report dyslalias. Memory troubles do not occur, as well as burning of the eyes, but some face furuncles. In premenstrual days she becomes more sensitive to odours.

Starting therapy (daily doses): Glutamine 125mg; pyridoxine 150mg; carbamazepine 200mg; amitriptylina 6mg; diazepam 5mg.  

 

05.10.2002: The first menstrual cycle after therapy improved and she was successful to feed with appetite. The mood improved, even if with some weeping and irritability. Colic  pain decreased to nearly nothing, She suffered from fewer headaches, so she   used an only one tablet of nimesulide 100mg for the usual 2-3 tablets, she had reduced unwillingness, not longer tachycardia.  Not more feelings of despair, no aggression, not more feelings of fainting, no mandibular tension, no mammary tension, perhaps she was more communicative.

She reported  still abdominal swelling, even after the menses. When started the therapy, she felt her much tired. Now she has even some depression, but without  bad thoughts. Hand oversweating reduced, but the armpit one unchanged. Over sensitivity to odours reduced. Therapeutic variation: glutamine stopped, and s-adenosil-l-methionine 200mg/daily went into the regimen.  

 

11.01.2003: She shows a more relaxed face and looks more beautiful, as many persons told her.  Fourth menses after therapy, her PMS nearly disappeared. Her husband says that she changed very much, in a  better way. They are left some hot flashes, some armpit oversweating, a light migraine and initial feeling sick, some furuncles. She did not feel  mammary tension as well as feelings of whole swelling anymore. 

With the SAMe she has improved decidedly her sexual satisfaction, and at work she is going well.  She has still fat hairs, and is always sensitive to the odours in the premenstrual period, even if some lesser. Some colic pain remained, and she is feeling tired, even out of the premenstrual period, but she admits that she had a great deal to do. The liver enzymes are increased, for which the carbamazepine stopped.

The therapy varied adding silimarine 400mg and oxcarbamazepine 150mg, both as  daily dosing.    

This is the report this woman wrote on 04.11,2002, of which I reproduced only meaningful parts, while the whole text is in the Italian version.

My name is M. L:, ... I had fallen into the abyss of the depression, because pathology..., called "the premenstrual syndrome." My first menstruation appeared when I was 12. I went through with a year without any problem, except weak colic pain that did not upset me at all. As time passed, however that pain has become always stronger; I spent whole days to bed with injections of BUSCOPAN (TM) [butilscopolamine bromide].

When this compound stopped to work, I assumed other commonly used antipain dugs.  My psychological state however was still intact ... More the months passed and more I realized that with the common antipain drugs I did not resolve anything. "When I was 14, for the first time I consulted a gynaecologist ... who ... prescribed me  Sinflex Forte (TM) [an antipain and muscle relaxing drug (?), not yet marketed], recommending me to begin the assumption of it some days before the menses, to prevent their discomfort.

The assumption of this drug went along for about two years. Initially the pain disappeared, however when the time went on it came out again, not limited to the abdomen only but even the pelvic zone, the anus, the vagina, with so violent contractions such to jeopardize even the urination.  Vomit did get out, as well as the fatigue, outbursts of crying for the pain that tormented me and for the fear I had to feel it, feeling sick, awful headaches.

So I was forced, on suggestion of the gynaecologist, to assume the oestrogenic-progestinal pill.  I was 17 when I began the treatment with the pill, which several consulted gynaecologists defined "a longtime therapy," ...  During 15 years of hormonal treatment ...  I experienced five types of it, since it did not succeed to find that ideal pill.  When I finished 20 years ... in spite of I was aware that with the hormonal treatment the violent aches had disappeared, ten days before the menses an indescribable fear towards the pains I suffered and however I was afraid of suffering again, griped on me.  I asked myself in continuation: "And now, if I feel painful, what I can do? How can I withstand it?"

In facts I began to live in a bit of terror for the  arriving menses. I cried and I was irritated till the starting of the menstruation and for the following 3-4 days.  As the years passed ...  besides the fear,  long fits of crying attacked me,  much more accentuated irritability, mainly with  aware aggressiveness, which I unloaded throwing objects on the floor or kicking the doors of my home. The nervousness griped on my throat, the esophagus, I felt suffocating, my mandible began to tremble in an uncontrollable way, I refused foods for two or more days. I did not want to go out and talk with other people, I stayed in bed for the whole afternoon crying without any stop, I warned faint feelings.  In my body I was feeling to die, I had feelings of despair and ... I did some bad [suicidal] thought.

My family by now doesn't know anymore, how they could  hand me; I took 10-15 drops bromazepan [about 7-8mg], but without any improvement. The depression came meeting me always faster, till I spoke with the psychologist ... I began to feel much better, when I could associate the technique of muscular relaxation to every negative situation ...  In spite of ... the hormone therapy, the abdominal and pelvic troubles, and mainly my psychological state worsened at all. In June 2002 ... a chief physician of gynaecology ... recommended me the immediate stop of the pill. It happened like the end of the world, since the use of the pill, in spite I realized  that now it was not working, it had become me essential for me, as a drug to which I do not could and I was unable to say not ...

The panic attacks became always stronger and now they could begin even 15 days before the menses. I was always more unsociable and without any interest.  The feelings of despair and death verged to reach the limit of my patience ... A cousin of mine told me, and accompanied me (with my husband) to consult a neurologist and psychiatrist ... He prescribed me a balanced therapy that, although made by low dosing drugs, elicited in me some disarrangement, like drowsiness, tiredness, mood switching, lack of concentration. In spite of it, the first menses during in the first month of therapy was for me a "new" experience; no panic attacks, colic pain, and all my previous symptoms  missed as for magic.  

The PMS did not appear even in the following menses. I began  so my second therapy month, and my body has overcome side-effects of the preceding month, even for the fact that my regimen had a drug changed.  There are however blue days, where I warn the desire of crying, but then it passes. During my duties, my colleagues said me they find me different, in comparison with some months ago, more serene, more open towards persons and the talk."  

 

03.05.2003: After stopping of the pill she has deflated. The control of the liver enzymes showed parameters in the normal range. At work her colleagues find her well, she speaks more, has more ideas, is better in the group. All, from the husband, find her changed in better. She had premenstrual periods without colic ache and without panic attacks, even if she suffered the springtime seasonal stress. In particular:

February 2003: In his premenstrual period she was unwilling for two days, with weeping, anxiety perceived mainly at the door of the stomach, irritable, unsociable, with pimples and hot flashes. No panic attacks, but great tiredness, which lasted even several days after the premenstrual period. The general health physician found her with low blood tension (ABT: 110-70 Hg), as usually she does in springtime, with tiredness, dizziness, blurred vision, tachycardia. She was given midodrine hydrochloride 2.5mg daily by the oral via. She thinks that the severity of this premenstrual syndrome was about 70% as compared of which experienced before the antistress drug therapy.

March, 2003: The premenstrual period (about seven days) featured nervousness, weeping, exaggerated worries as for the work of the husband, hot flashes, lack of appetite that then went on. She did intake little amounts of food, and the weigh did not change, but she had the feeling of her stomach door closed. She did not worry about her coming menses. She thinks that the severity of this premenstrual syndrome was about 70% as compared of which experienced before the antistress drug therapy.
At the March end she had flu with vomit and stomachache.

April 2003: She suffered from nervousness and irritability in her premenstrual period, with a crying fit, during which she warned a suffocation feeling, but weeping stopped after some minutes. She has eaten without any problem. She thinks that the severity of this premenstrual syndrome was about 80% as compared of which experienced before the antistress drug therapy.

3 May 2003: Her premenstrual period is now running, and it seems less severe, in comparison with the preceding month.

Therapy prescribed, daily doses, by oral via: Amitriptyline 8mg, diazepam 5.6mg, creatine 1 g, SAMe 200mg, pyridoxine 150mg, oxcarbamazepine 150mg. 
 

 
08.11.2003: Altogether she is doing well, but she had several blood losses from the uterus and she was given a curettage. The premenstrual syndrome is decidedly reduced, even when other reasons of stress added. On October, she felt the seasonal stress, with working problems, for which she had impatience versus nursed patients. In premenstrual days she has pimples in her face.

Unchanged therapy.

This is the written note by the patient I got on 11.08.2003 with the time course of the six last months of drug therapy.

" In May I had an other consultation with Dr Cocchi, very expected by myself because, since the spring becoming, my psychosomatic balance [or, better: My somatopsychic balance?] inclined to deteriorate. The anxiety was increasing and with it, mainly in stressing moments tied to my work turn, first the tachycardia, then fit of crying and air hunger.

Physical tiredness occurred also, and I perceived it particularly to hips and to the inferior limbs muscles, so that I laboured in going up down the stair and in after short walking. On advice of my family practitioner, I left my work for seven days, looking for restoring so what I had previously reached. Only adding diazepam even to the mornings and creatine, my balance recovered.

As for the following May and June, they were two particular and complicated months. Since March-April between two menses I had blood losses to which I did not mind and I did not want to consult a gynaecologist.

Subsequently, the blood losses transformed in a continuous menses that covered entirely the May month and June. In facts the menses came regularly, but at the end of it, after four or five days, it began a second blood loss, which fully lasted between a cycle and the following.

I started to have agitation, and often to bother me, with the always fixed thought on that happening, and I came to cry because I feared that could be a cancer. My family practitioner convinced me to consult a gynaecologist, who proposed me an operation of curettage to solve the problem. The US scan diagnosed the presence of microcystes into the left ovary, in addition of the fibroma, of which I was already informed. In those two months I was much anxious, with strong stomach pain and retchings (not in the premenstrual period).

July: The hospital that had to do my curettage communicated me the date of the intervention with only three days in advance. I was forced to stop all the therapy in course, because the curettage should be acted in general anaesthesia [a prudential attitude, but not an essential one]. The family practitioner then prescribed me 15 rest days, with absence from the work, a period I lived as a nightmare. I feel me without any energy, with a strong back pain at the level of the kidney areas, and my mood worsened in noticeable way.

I was in a blue mood, with long crying moments, oversweating, some air hunger. I did not succeed to feed me, even for the hot weather, I was always home stretched out on the bed or on the couch because my lumbar pain. When I walked in the street or in the courtyard the pain increased.

When I was home alone, it seemed that the whole world was gaudy against me, and I slept much either by day and by night. The haemorrhage after surgery did not elicit any problem, but according to Dr Cocchi, the amitriptyline grew to 16mg, daily.

August: A calm month both at home and at work, and the general being improved in notable measure. The histological report resulted negatively. During the first two days of the menses I was successful to feed me only a few following the nausea and the hypersensitivity to the odours. I had strong hot flashes, which let me uneasiness on the job. For the remaining things, not menstrual pain, in spite of the curettage and not panic attacks occurred.

September: An exceptional month, even because in summer holidays during the first two weeks. In holiday I was relaxed, taking part in the proposed activities, I went out for some excursion or I rested. Before the departure, in accord with Dr Cocchi, I reduced the amitriptyline to 12mg. The climate was warm but well airy. I came back at home in the 4-5 days preceding the menses. This time however the appetite was excellent, to such a point that I had to halve every ration, because the hunger I felt was excessive, and however I increased two kg. The psychophysical state was well, without anxiety, but light irritability, many bursts of heat, which unfortunately continued, and I found me in a boring bath of the sweat.

October: In premenstrual period I did not have any nausea, and so I successfully ate without any problem. I had annoying hot flashes, lumbar pain and, desultorily, light tachycardia. I felt me as sensitive, with vulnerability to some events, as the memory of what I lived, with related psychological changes.

To conclude, I am doing well, different, even if sometimes I fear to come back as I was. I think that me even the psychotherapist helped me a lot to correct my attitudes or behaviour related to wrong entangled ideas on me the same. Because the depression I felt me as different, not normal, and I accused me of what was happening and I made me guilty. This guilt sense overpowered me, giving me a kind of suffocation, and limited me not only in the couple's life, but even in the work.

 Now, thanks the drug therapy and to the psychotherapy I can control better what happens me. So, because I feel myself more sure, and I succeed to express in a better way what I think or I feel in a particular circumstance.

About two weeks ago, during a working time, a colleague with whom I am rarely in a couple, said me "L, I do not know what you have had, and has done, but you are much changed." I perceived this observation much favourably, even if I did not answer, for the delicacy of the problem, but I only smiled.

The depression is a terrible illness, and anyone who did not experience it, does not understand it.

June 2004: She is doing well. Now, her face is much different, more relaxed and more oval. Her premenstrual phases are much bearable. Not all the months she had headaches. Sometimes she had nausea and lack of appetite. The pain is nearly missing. She has some metrorrhagias and she assumes a progestinal drug for it. Groundless tachycardia happened and she had some low blood tension. Between February and April she had a depressive moment, primarily of the asthenic type. Her job is going well. Now, she attends a professional course to improve her situation in her work.

Therapeutic variation (daily doses, by the oral via): Diazepam stopped; Bromazepam 2mg; SAMe 100mg; pyridoxine 37.5mg.

 

This is the written note she bought to me on 05.06.2004.

"Since November, when I did the last checkup with Dr Cocchi, till now my health situation improved. The menses did never create any anxiety problems, phobias, want to die. By now I do not have any fear of them.

However, during these months some episodes of nausea, lack of appetite, headaches occurred but not to every cycle. What now worries me as a few are the uterine blood losses that are relapsing, in spite of the curettage I underwent the last year. This doesn't happen every month, a fact that causes me some emotional stress, even if I am under control of an endocrinologist.

In spring, or better since February, I started to have tachycardia at rest, mainly when I was going to fall asleep, or in home, in company of persons during relaxing moments, without any specific cause for their onset.

This troubles did not encompass the premenstrual week only, but it had a random onset. I felt a sense of oppression to the chest, my temples pulsated strongly, as even the carotids, and I had air hunger. When I was in bed, I had to lead myself in sitting position because the suffocation feelings and the need to breathe deeply.

By minding the season change, as previously Dr Cocchi advised me, I added eight drops of diazepam [ 1.6mg] in the mornings. This year did not succeed in bearing it. I was not able to face the day. I was sleepy, although busy in the study [she is attending a professional course] and in the work, and I felt much asthenic. I had to stop this morning's diazepam. With the usual therapy I felt me better, even if however the tachycardia did not disappear, and I had it throughout all April, disappearing slowly. On May low blood tension occurred, and I did face it with midodrine drops, the general practitioner prescribed me.

The premenstrual syndrome disappeared, or at least not there are not more those dreadful days that came back every month. Sometimes I have some nervousness, some sudden mood change of depressive type, but sometimes I laughing till the tears. I am attending a course of specialization for nursing, and in spite of my initial perplexity, at the end I find me well there. However, it was, at least in the first times, a reason of further stress.

To guess, I perceive myself as changed, and the persons with whom I am in touch every day go on to observe it, either work colleagues and family members. They reported me that I have my face features more serene and relaxed.

 As for me, I am ready to reduce the drugs if Dr Cocchi thinks it suitable [???? And so, even if we are dealing with a substituting therapy?]. I think still now to what happened to me and to the fact of not being aware that I needed a different help, by leaving to spend so many years and by living with horrible mood and desire to die. The depression is an awful state, and some weeping in my premenstrual days is neither distantly comparable to what I suffered before I started this drug therapy.

June 2004, after two weeks from the latest checkup, by phone: She says that she did not face the lightening of drug therapy. Now, she is depressed, crying, much irritable. Even the patients elicit to her much nervousness, but she controls herself and does not show it.

The premenstrual period that occurred meanwhile, was nearly a return to the past, as ugly as it was.

I advised her to return to the preceding drug therapy, by stopping bromazepam, and taking diazepam and doubled doses of SAMe and pyridoxine.

 

First 10 days of the January 2005: This is sixth checkup after 27 months of antidepressant-antistress drug therapy. At the actual doses of drugs the premenstrual period is much bearable, if not nonexistent.

She has ended brightly the course of health specialization and this has reduced the causes of stress. In the change of the season she has been a little dysphoric, moreover shows traces of fatiguing the greater working load. Her mood is currently normal.

She goes on with the current therapy.

First ten days of June 2005: The premenstrual period is much tolerable. Not all the months she had the headache. Some time she has nausea and lack of appetite. Pain did not come out. She had metrorrhagia, and she is under treatment by the low dosing luteal hormone. It appeared some casual tachycardia, with pallor episodes and low blood tension. The job is going well.

Therapeutic variation (daily doses, by the oral via): Bromazepan 2mg.

First 10 days of December 2005. Altogether she is well off. Now, the menstrual cycle is regular. She did not suffer anymore from metrorrhagia. Lately she had some attacks of frontal and centre skull headaches. The job is always going well. She attends a gym. The face is more serene, more relaxed. She thinks she sleeps still too much [Is it a compensation symptom?].

Therapeutic variation (daily doses, by the oral via): Bromazepam 1.6mg; amitriptyline 6mg; oxcarbamazepine 300mg; pyridoxine 75mg.

 

Discussion.  

The presumed action of the female steroid hormones on the release of some brain neurotransmitters involved in the mood control, does not enough explain many symptoms of that woman. Not specific symptoms of the PMS  were found even in other stress reactions in males male (Cocchi, 1998).

Though about the 90% of the women are suffering from PMS, the fact that about 10% of them is free of it, needs further explanations.  Since the amount of stress reactions  depends on an either genetic threshold either an acquired one, several women may not suffer from PMS because a very high threshold of response to stresses. It is enough easy to understand what I mean for a genetic threshold.

For an acquired good threshold of response to the stress,  I mean a threshold that did not have stable alterations of the hippocampus-cortico-suprarenal double feedback, otherwise induced by burden risk factors that mostly acted in pre- peri- neonatal time (Sapolsky et al., 1990).

 But when these women are fighting other stresses, without any relationship with the menses' cycle, the SPM can emerge, since the sum of the stresses surpasses even the resistance of the high threshold they own.  I selected the case-history here reported as first therapeutic approach, because its singular features:

- the PMS was particularly imposing;

- an estrogenic-progestinal therapy of 15 years, with five different combinations of the two hormones,  had given disappointing results, mainly on psychic symptoms;

- the psychotherapy, after an initial improvement, could not maintain it.  

Therefore the hypothesis of an antistress therapy by drugs should were justified from the ineffectiveness of both the hormonal and the psychological treatment, beyond  the presence of stress symptoms, mainly psychic ones, other than those of the PMS.  

The demonstration that the drug therapy should be individually tailored, to act on stress reactions that are in its turn individualized,  may be found in the fact that I had to stop the glutamine, a physiological compound of primary importance in the balance of brain neurotransmitters, where it is the precursor of the glutamic acid and of the GABA.    

Twenty-six menstrual cycles with very reduced PMS can always be debatable for this  different therapeutic approach, in a form of PMS no longer responder to  traditional treatments. However, the thing has worked since the first cycle, following the drug therapy I theoretically foretold.

 With the last updating on December 2005, the report of this case history ends, after 39 months of antistress drug therapy.

 

References.

Cocchi R.:  Pre-menstrual syndrome as the paradigm of an internal biochemical stress. The 2nd World Congress on Stress, Melbourne, 1998.

Cocchi R.:   Unwanted effects of drugs and premenstrual syndrome. The 2nd World Congress on Stress, Melbourne, 1998.

Cross GB; Marley J; Miles H; Willson K.: Changes in nutrient intake during the menstrual cycle of overweight women with premenstrual syndrome. Br J Nutr 2001, 85: 475-482.

Douglas S.: Premenstrual syndrome. Evidence-based treatment in family practice. Can Fam Physician 2002, 48: 1789-1797.

Mortola J.F.: The premenstrual syndrome. Curr. Ther. Endocrinol. Metabolism. 1997, 6: 251-256.

Sapolsky R.M. et al.: Glucocorticoid feedback inhibition of adrenocorticotrope hormone secretagogue release. Neuroendocrinology 1990, 51: 328-336.

  First on Internet on January 2003. Copyright by Renato Cocchi, 2003

 

Author's address: Dr Renato COCCHI, via Rabbeno, 3,

42100 Reggio Emilia (Italy)

renatococchi@libero.it

 

Testo in italiano

Premenstrual syndrome

Drug modulation of stress reactions.

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