Potential strategies to avoid progestogen-induced premenstrual disorders

Non-hormonal approaches to premenstrual syndrome (PMS) treatment such as selective serotonin reuptake inhibitors are by no means effective for all women and frequently we must resort to endocrine therapy. During many of the hormonal approaches, PMS-like symptoms can be introduced or re-introduced during the necessary cyclical or continuous progestogen component of the therapy. This is seen with combined oral contraception, progestogen only contraception, progestogen therapy for heavy menstrual bleeding and endometriosis, sequential hormone replacement therapy and any therapeutic strategy for premenstrual syndrome where it is necessary to provide endometrial protection, including estrogen suppression of ovulation or add-back during gonadotrophin releasing hormone suppression. The link to progestogen is very often missed by health professionals. When the pattern of symptoms mimics the cyclicity of PMS, it is termed progestogen-induced premenstrual disorder. The need to use progestogen to protect the endometrium from the proliferative actions of estrogen can pose insurmountable difficulties in managing premenstrual disorders. In the absence of any really useful evidence, nearly all practice in this area depends on clinician experience. We cannot afford to wait for adequate research evidence to be produced - it never will - and so we must rely on empirical findings, clinical experience, theoretical strategies and common sense.     

Psychotropic medications and other non-hormonal treatments for premenstrual disorders

Selective serotonin re-uptake inhibitors have well-established efficacy for severe premenstrual syndrome and premenstrual dysphoric disorder. Efficacy has been reported with both continuous dosing (all cycle) and intermittent or luteal phase dosing (from ovulation to menses). Efficacy may be less with intermittent dosing, particularly for premenstrual physical symptoms. The efficacy of symptom-onset dosing (medication taken only on luteal days when symptoms occur) needs further systematic study. Women going through the menopausal transition may need to adjust their antidepressant dosing regimen due to the change in frequency of menstruation. Anxiolytics, calcium, chasteberry and cognitive-behaviour therapy may also have a role in the treatment of premenstrual symptoms.     

Treatment of premenstrual disorders by suppression of ovulation by transdermal estrogens

The understanding of the cause and treatment of premenstrual disorders is confused but it is essentially the result of cyclical ovarian activity, usually ovulation, and an effective treatment should be by suppressing ovulation. This can be done by an oral contraceptive but as these women are progestogen intolerant the symptoms may persist becoming constant rather than cyclical. Alternatively, transdermal estradiol by patch, gel or implant effectively removes the cyclical hormonal changes, which produce the cyclical symptoms. A shortened seven-day course of a progestogen is required each month for endometrial protection but it can reproduce premenstrual syndrome-type symptoms in these women. Gonadotropin-releasing hormone with 'add-back' is effective in the short term. Laparoscopic hysterectomy and bilateral oophorectomy with adequate replacement of estrogen and testosterone should be considered in the severe cases with progestogenic side-effects.     

Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder are triggered by hormonal events ensuing after ovulation. The symptoms can begin in the early, mid or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormone. Although evidence for a hormonal abnormality has not been established, the symptoms of the premenstrual disorders are related to the production of progesterone by the ovary. The two best-studied and relevant neurotransmitter systems implicated in the genesis of the symptoms are the GABArgic and the serotonergic systems. Metabolites of progesterone formed by the corpus luteum of the ovary and in the brain bind to a neurosteroid-binding site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its configuration, rendering it resistant to further activation and finally decreasing central GABA-mediated inhibition. By a similar mechanism, the progestogens in some hormonal contraceptives are also thought to adversely affect the GABAergic system. The lowering of serotonin can give rise to PMS-like symptoms and serotonergic functioning seems to be deficient by some methods of estimating serotonergic activity in the brain; agents that augment serotonin are efficacious and are as effective even if administered only in the luteal phase. However, similar to the affective disorders, PMS is ultimately not likely to be related to the dysregulation of individual neurotransmitters. Brain imaging studies have begun to shed light on the complex brain circuitry underlying affect and behaviour and may help to explicate the intricate neurophysiological foundation of the syndrome.     

Classification of premenstrual disorders as proposed by the International Society for Premenstrual Disorders

Premenstrual disorders have been recognized as affecting innumerable women for decades but unlike most other medical conditions universally accepted criteria for definition and diagnosis are not established. Although premenstrual syndrome (PMS) occurs throughout reproductive life, there are some women who become particularly troubled. Those approaching the menopause may also have a mixture of PMS and menopause symptoms, not to mention heavy periods. Furthermore, some of the symptoms are similar in nature and so it is a challenge to identify which set of symptoms belongs to which spectrum. This is an area that has not been explored well. Various classifications have been proposed over the last few decades. A further effort towards the classification was made by an international multidisciplinary group of experts established as the International Society for Premenstrual Disorders (ISPMD) in Montreal in September 2008. Their deliberations resulted in a unified diagnosis, classification of premenstrual disorders (PMD) along with their quantification and guidelines on clinical trial design. This classification of PMS is far more comprehensive and inclusive than previous attempts. PMD in the ISPMD Montreal consensus are divided into two categories: Core and Variant PMD. Core PMD are typical, pure or reference disorders associated with spontaneous ovulatory menstrual cycles while Variant PMD exist where more complex features are present. Further, the consensus group considered that PMD may be subdivided into three subgroups predominantly physical, predominantly psychological and mixed. Variant PMD encompass primarily four different types; premenstrual exacerbation, PMD with anovulatory ovarian activity, PMD with absent menstruation and progestogen-induced PMD.     

Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Benign prostatic hyperplasia (BPH) is very common in aging men and causes lower urinary tract symptoms (LUTS), which decrease health-related quality of life. A number of evidence suggests that other than ageing, modifiable factors, such as increasing prostate volume, obesity, diet, dyslipidemia, hormonal imbalance, hypertension, metabolic syndrome, alcohol, and smoking, also contribute to the development of BPH and/or LUTS. More recently, erectile dysfunction (ED) has been linked to LUTS/BPH as a part of this syndrome, suggesting that patients with BPH or LUTS easily develop ED, and that LUTS/BPH symptoms often coexist with ED. This article focuses on the epidemiology and risk factors of the combined phenotype LUTS/BPH – ED.     

Treatment of premenstrual syndrome: a decision-making algorithm

The aim of this short paper will be to guide the clinician through the plethora of possible interventions to help them to individualize treatment for their patients with PMS. The discussion will highlight management principles rather than evidence per se. It uses as its basis an updated version of the treatment algorithm published by the RCOG in its Green Top Guideline no. 48 on the management of PMS.     

Severe premenstrual syndrome and bipolar disorder: a tragic confusion

Bipolar disorder and severe premenstrual syndrome (PMS) have many symptoms in common, but it is important to establish the correct diagnosis between a severe psychiatric disorder and an endocrine disorder appropriately treatable with hormones. The measurement of hormone levels is not helpful in making this distinction, as they are all premenopausal women with normal follicle-stimulating hormone and estradiol levels. The diagnosis of PMS should come from the history relating the occurrence of cyclical mood and behaviour changes with menstruation, the improvement during pregnancy, postnatal depression and the presence of runs of many good days a month and the somatic symptoms of mastalgia, bloating and headaches. Young women with severe PMS do not respond to the antidepressants and mood-stabilizing drugs typically used for bipolar disorder.     

Epidemiology of sarcopenia

Reproduced with permission     

Musculoskeletal disorders and productivity

Conclusion On balance, the evidence supports an association of higher productivity increases with lower MSD rates and greater reductions in MSD rates. Across all industries for which data were available, lower MSD rates were significantly correlated with higher productivity increases. Since both changes in MSDs and in productivity have many varied causes, the effects of efforts specifically intended to reduce MSDs are difficult to isolate from these data. Nevertheless, in two subsets of industries those effects may be more likely to be discernible: industries with the largest reductions in MSD rates would be more likely to have made changes intended to reduce MSDs, and industries with lower productivity growth may reduce the effects of unrelated productivity gains on MSD/ productivity observations. Statistically significant correlations between reductions in MSDs and increases in productivity were found among both of these groups. In addition, among industries with the highest MSD rates in 1992, the extent of implementation of ergonomic controls was significantly correlated with increases in productivity. A special thank you is extended to William Weber, William McCarthy, and Linda Garris of the Bureau of Labor Statistics, Office of Safety, Health and Working Conditions, for providing MSD industry data for 1992 and 1998. The opinions expressed in this article are those of the authors and do not necessarily reflect the official positions of the department or agency with which the writers are affiliated. Jens Svenson is currently on detail to the Office of Management and Budget.