The diagnosis and management of premenstrual dysphoric disorder in primary care

Ki-Yan Mak 麥基恩

HK Pract 2005;27:108-113

Summary

Premenstrual physical and psychological symptoms among menstruating women are very common, and can be called "Premenstrual Syndrome" (PMS). But when these symptoms become so severe as to disturb their daily functioning (or the functioning of those around them, especially their spouses), it becomes Premenstrual Dysphoric Disorder (PMDD) which is a treatable disorder. Frontline doctors, especially primary care physicians and gynaecologists should be well trained in the management of these disorders, medically and psychosocially. The judicial use of Selective Serotonin Reuptake Inhibitors (SSRIs) is the mainstay of therapy, and supplemented by lifestyle adjustment and dietary/exercise advice. Other medications may be tried when the response is not satisfactory or in the presence of comorbidities. Additional research on PMDD is still needed, especially on cultural differences, but this should not prevent doctors in treating the disorder promptly and properly.

摘要

行經期婦女常有月經前生理和心理症狀，稱為經前綜合症(PMS)。如果這些症狀嚴重到影響她們自己或其他人， 特別是配偶的日常生活時，就成為經期前情緒異常症(PMDD)─一種可治療的疾病。前線醫生，尤其是家庭醫生和婦科醫生， 要有適當的訓練，從生理和心理方面治療病人。目前主要是使用選擇性血清素攝取抑制劑治療， 同時輔以改變生活和飲食習慣和適當運動。反應欠佳者，可試用其他藥物。本病還有待進一步研究，特別是文化差異的影響， 但這並不妨礙醫生及時適當醫治病人。

Introduction

Premenstrual symptoms of different degrees are extremely common, and it was in ancient times described as a "virgin's disease", as married women were generally pregnant without regular menstrual cycles. During the 5^th century B.C., Hippocrates wrote that retained menstrual blood could cause psychological symptoms, and described women developing suicidal ideas prior to the onset of menses.¹ In 1931 Frank² coined the term Premenstrual Tension Syndrome (PMTS) in 15 women experiencing physical and psychological symptoms before menstruation. Such premenstrual symptoms often puzzled primary care doctors as to whether they are normal or pathological (physically or psychosomatically). In 1987, the DSM-III-R³ included the term Late Luteal Phase Dysphoric Disorder (LPPDD) which was changed to Premenstrual Dysphoric Disorder (PMDD) in DSM-IV in 1994⁴ with a slight modification of the diagnostic criteria attached to Appendix B (meaning there was insufficient information to warrant inclusion as official category).

Clinical features

PMDD is a cyclical disorder characterized by depressed or labile mood, anxiety, irritability, anger and other psychological symptoms (Table 1) occurring exclusively during the two weeks preceding menses (the post-ovulatory, premenstrual period or late luteal phase of a woman's ovulatory cycle). The symptoms occasionally do occur at ovulation, but should remit within a day or two after menstruation. Strictly speaking, the symptoms should disappear during the rest of the menstrual cycle (at least 7 to l0 days), though the clinical picture may be affected by comorbidities. The disorder often increases with age until menopause, and some women experience the disorder for the first time after childbirth. Quite often, PMDD patients are more likely to have post-partum depression, and have more psychosocial difficulties when going through the menopause. In order to qualify for PMDD, the disorder should be severe enough to affect occupational and social functioning, otherwise the clinical picture should be labelled as the more common Premenstrual Syndrome (PMS). However, if there is an underlying disorder (such as migraine, diabetes, anxiety or mood disorders, etc.) which gets worsened premenstrually, this may be called Premenstrual Exacerbation (PME).⁵ Theoretically, when the underlying disorder is well treated, such exacerbation should also disappear.

Epidemiology

The above symptoms can occur at any age, but only in women who menstruate. They are thus absent during pregnancy or after menopause. It is uncommon in women who are breast feeding especially before menses reappear. Up to 75% of adult menstruating women experience some physical or psychological symptoms before menses,⁶ and in Hong Kong, Chan and Mak⁷ also found quite a high percentage of Chinese women in a general practice having premenstrual symptoms. As physical exercises may have some protective effect, the percentage of PMS may vary in different countries. Nevertheless, about 2.5% to 5% are severe enough to be classifiable as PMDD.⁸ Women commonly report that their symptoms worsen with age until relieved by the onset of menopause.

Aetiology

1. Hormonal imbalance

So far no specific genes have been identified, but twin studies do suggest that PMDD is biological in origin.⁹ There is also no consistent hormonal imbalance found in PMDD.¹⁰ At one time, Dalton¹¹ suggested an ovarian hormones hypothesis _ an imbalance between oestrogen and progesterone, with a relative deficiency of the latter, thereby meriting the use of progesterone suppositories, but the theory has been challenged.¹² Nevertheless, recent findings suggest that the progesterone metabolite, allopregnanolone, which modulates GABA receptor functioning, may be related to PMDD severity¹³ and that the GABAA (gamma-amino-butyric-acid) receptor complex may be altered in PMDD women.¹⁴

2. Neurotransmitters dysreuglation

The serotonin hypothesis suggests that there is a cyclical trigger of serotonin dysregulation (reduced 5HT) resulting in irritability, dysphoria, impulsivity, etc. This is further evidenced by finding of reduced platelet uptake of 5HT (somewhat similar to anxiety and depression states) during the period,¹⁵ and the use of m-CPP (5HT agonist) may improve the mood. Besides 5HT, other neurotransmitters may also be involved, as GABA level is also low in the patients,¹⁶ and opiate antagonists studies suggest a possible acute withdrawal of endogenous opioids during the late luteal phase.^{17, 18}

3. Psychosocial hypothesis

A woman's conscious perception of her femininity in a male-dominated society. This is affected by social learning and can be culture-bound (as considered normal womanhood in some cultures).

Management

A good history and physical examination including a pelvic examination can help to distinguish PMDD from other medical or physical disorders (Table 2), and laboratory tests are sometimes indicated. The patients should keep a diary regarding the various symptoms, as this can help to differentiate PMDD from other physical or psychiatric disorders.

Treatment

Proper psychoeducation is essential for the management of PMDD (and perhaps also for PMS), not only given to the patients but also to their family members especially the spouses. Lifestyle changes with adjustment of dietary contents (increase intake of complex carbohydrates with decrease in salt intake) may be helpful. Some women would find chocolates helpful, perhaps because of its chemical contents (phenylethylamine which improves mood, methylxanthine which possesses stimulating effects, and N-acylethanolamine which increases serotonin). However, excessive caffeine (tea or coffee) should be avoided during the late luteal phase. Besides, adequate exercise, be it vigorous or relaxation type, is very helpful (not only psychologically, but also physically through increased release of endorphins and phenylethylamine), even if performed just at the onset of PMDD symptoms.

For PMDD, a more definitive treatment is needed. The FDA of the United States of America approved in 2000 the use of "Sarafem" (fluoxetine) as a specific medication for PMDD. Besides fluoxetine,¹⁹ other SSRIs including paroxetine,²⁰ sertraline²¹ and citalopram²² have been tried. Clomipramine²³ and venlafaxine²⁴ which also have potent effects on serotonin are also useful. The onset of action is usually much earlier (sometimes within a day or two) than in the treatment of depressive or anxiety disorders, and the medications can be given continuously or intermittently during the luteal phase only.²² This is perhaps because SSRIs indirectly increase the synthesis of allopregnanolone from progesterone which modulates GABA receptors thereby relieving the symptoms.²⁵ These SSRIs are also able to reduce physical symptoms like breast tenderness and bloating; and intermittent and post-ovulatory dosing may decrease the adverse side-effects such as sexual dysfunction. The other antidepressants such as tricyclics or bupropion have not been found useful, except for comorbid depressive disorders.

Symptomatically, the various physical symptoms of PMDD can be alleviated by the use of diuretics and analgesics. Medications for the treatment of co-existing anxiety are helpful but there should be caution in using benzodiazepines,²⁶ as there is the danger of addiction and abuse. Vitamins and mineral supplements are perhaps more useful psychologically, except calcium carbonate (80mg per day) which appears better than placebo²⁷ but less than SSRIs. Magnesium supplements (360mg per day) may decrease fluid retention and thus relief some PMDD symptoms.²⁸ Pyridoxine (vitamin B6) produces only a mild effect if any,²⁹ but caution should be taken concerning its potential neurotoxic effect with doses greater than 100mg per day.

As a last resort, the suppression of ovulation, either medically³⁰ or surgically,³¹ can abolish premenstrual symptoms. Gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide, goserelin and nafarelin, which act on the hypothalamus to decrease Follicular Stimulating Hormone (FSH) and Leuteinising Hormone (LH) thereby lowering oestrogen and progesterone synthesis, can help some PMDD patients but not for severe dysphoria.³² Danazol which suppresses the hypothalamic-pituitary-gonadal axis has been used with mixed results, but both its short-term and long-term side-effects can be considerable,³³ especially if used for more than 6 months. The use of oral contraceptives to regulate the menstrual cycle is controversial, and oestrogen alone may worsen the mood symptoms.³⁴ Nevertheless, a recent study found that an oral contraceptive that contains drospirenone (a progestogen with spirolactone properties) and ethinyestradiol has been found useful on the general well-being and fluid-related symptoms.³⁵

As adjunct to medications, cognitive-behavioural therapy to correct distorted thinking towards the effects of PMDD and inter-personal therapy (including marital counselling) to improve social interactions are quite useful.

Conclusion

For centuries, many people of either gender are unaware that PMDD is a disorder but accept it as "part of a woman's fate".³⁶ However, the psychosocial consequences in some women do cause concern, not only to the women themselves but also to the family and even the society at large. Women feel they have two different personalities, like Dr. Jackle and Mr. Hyde, before and after menstruation. Some have even used PMDD as a legal defense in trials of murder and child abuse.³⁷ The diagnosis of a PMDD is not a made-up disease, and should merit the full attention of gynaecologists and primary care doctors. With better understanding of the bio-psycho-social factors involved and with better medications being developed, the unnecessary periodic pains and sufferings of women during their prime of life can be alleviated, and may even change the social functioning of the female gender in society.

Key messages

1. Physical and psychological changes occur throughout the menstrual period, but often markedly distressing during the premenstrual period, causing clinical significant symptoms and signs.
2. The diagnosis of Premenstrual Dysphoric Disorder can be made if there are associated psychosocial dysfunctions.
3. In a way, the diagnosis is not uncommon in clinical practice, but many doctors are not sensitive enough to enquire about this condition.
4. Prompt diagnosis and proper management can be of benefit not only to the women concerned, but also to their family members and significant others.
5. There are currently quite a number of effective therapies for this disorder, and primary care doctors are in a good position to educate and to treat this disorder.