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.     

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.     

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.     

Systemic lupus erythematosus and hormone replacement therapy

The indications for hormone replacement therapy (HRT) in postmenopausal women is the treatment of climacteric symptoms and the prevention of osteoporosis. Women with systemic lupus erythematosus (SLE) are more likely to have a premature menopause, osteoporosis and cardiovascular disease. HRT can induce SLE flares and cardiovascular or venous thromboembolic events. Therefore it should not be used in women with active disease or those with antiphospholipid (aPL) antibodies. In general, it should be used only for patients without active disease, a history of thrombosis or aPL antibodies. Non-oral administration of estrogen is recommended because of its lesser effect on coagulation. With regard to the progestogen, progesterone or pregnane derivatives are preferred. Otherwise, non-estrogen-based strategies should be used.     

Epidemiology of premenstrual symptoms and disorders

The aim of this paper is to review published literature on the types and prevalences of premenstrual disorders and symptoms, and effects of these on activities of daily life and other parameters of burden of illness. The method involved review of the pertinent published literature. Premenstrual disorders vary in prevalence according to the definition or categorization. The most severe disorder being premenstrual dysphoric disorder (PMDD) affects 3-8% of women of reproductive age. This disorder focuses on psychological symptoms whereas global studies show that the most prevalent premenstrual symptoms are physical. Both psychological and physical symptoms affect women's activities of daily life. A considerable burden of illness has been shown to be associated with moderate to severe premenstrual disorders. In conclusion, premenstrual symptoms are a frequent source of concern to women during their reproductive lives and moderate to severe symptoms impact on their quality of lives.     

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.     

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.     

Interactions Among Sexual Activity,Menstrual Cycle Phase,and Immune Function in Healthy Women

Past research has found menstrual-cycle-related changes in functional immune response; we examined if sexual activity also changed markers of immune defense. We followed 32 naturally cycling women (15 sexually active with a partner ≥ 1 time/week, 17 sexually abstinent for the last four months) over one menstrual cycle. Participants provided serum and saliva samples at menses and ovulation, and additional saliva samples at midfollicular and midluteal phases. At each phase, participants also self-reported symptoms associated with colds, flu, pain, menstrual discomfort, and premenstrual syndrome. We tested saliva and serum for ability to kill Escherichia coli or Candida albicans, and serum for complement protein activity. For serum-mediated pathogen killing, among sexually active women only, there was a significant midcycle decrease in killing of E. coli. For saliva-mediated pathogen killing, among abstinent women only, there was a significant midcycle decrease in killing of E. coli, and midcycle increase in killing of C. albicans. Sexually active women had significantly lower complement activity than abstinent women overall. Finally, both groups reported lower physical symptoms at midcycle and higher symptoms at menses. There may be important differences in immune function between healthy women who are sexually active versus abstinent. Further replication is warranted.     

Gonadotrophin receptor hormone analogues in combination with add-back therapy: an update

Gonadotrophin receptor hormone analogues (GnRHa) have been used in a range of sex hormone-dependent disorders. In the management of premenstrual syndrome, they can completely abolish symptoms. The success of GnRHa in the treatment of endometriosis and adjuvant therapy in the management of fibroids is proven. This efficacy does not come without a cost and the side-effects of the hypo-estrogenic state have limited their application. The use of add-back therapy to counter these effects has enabled wider application, longer durations of treatment and an increase in compliance. This review article is an update on the evidence supporting gonadotrophin receptor hormone analogues in combination with add-back therapy.     

Use of endocrine hormones for treating depression

Disturbances in some endocrine hormones have been implicated in the pathophysiology of depression. Some of these hormones (and drugs that affect hormone function) have been used as therapeutic agents for the treatment of depression, especially adrenal, thyroid, and gonadal axis hormones. Open-label and controlled studies of various drugs that directly suppress or inhibit adrenal axis function have shown some benefit for the treatment of major depression, including treatment-resistant depression. Thyroid hormone augmentation is effective for nonresponders to antidepressant agents, although it has not been studied extensively. Estrogen may improve mild mood symptoms in perimenopausal women but may not be effective alone for major depression. Evidence of the antidepressant effects of testosterone in men is inconsistent, with mixed results from controlled studies. The adrenal steroid hormone dehydroepiandrosterone has an important role in mood regulation and may have significant antidepressant effects.     

PMS and PMDD in the domain of mental health nursing

Premenstrual syndrome (PMS) is a complex cluster of symptoms that occurs 7 to 14 days prior to menses and ends 1 to 2 days after menses. Premenstrual syndrome symptoms can create severe, debilitating psychological and physical problems. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) provides criteria for premenstrual dysphoric disorder (PMDD), which can be considered the most severe presentation on the PMS continuum. A critical part of determining the diagnosis is evaluating the timing of symptoms. True PMS only occurs during the luteal phase of the menstrual cycle, with a symptom-free period during the follicular phase. After identifying a diagnosis of PMS or PMDD, the first-line treatment of these symptom clusters continues to be lifestyle changes, including stress management, healthy diet, regular aerobic exercise, cognitive-behavioral therapy, and fortified coping strategies. Women whose symptoms are not controlled adequately with lifestyle modifications may benefit from medications. Possible medication recommendations include selective serotonin re-uptake inhibitors (SSRIs), diuretics, gonadotropin-releasing hormone (GnRH) agonists, and vitamin and mineral supplements.     

Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates

It has long been recognized that women are at a higher risk than men to develop depression and that such risk is particularly associated with reproductive cycle events. Recent long-term, prospective studies have demonstrated that the transition to menopause is associated with higher risk for new onset and recurrent depression. A number of biological and environmental factors are independent predictors for depression in this population, including the presence of hot flushes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues, ethnicity, history of stressful life events, past history of depression, body mass index, socioeconomic status and the use of hormones and antidepressants. Accumulated evidence suggests that ovarian hormones modulate serotonin and noradrenaline neurotransmission, a process that may be associated with underlying pathophysiological processes involved in the emergence of depressive symptoms during periods of hormonal fluctuation in biologically predisposed subpopulations. Transdermal estradiol and serotonergic and noradrenergic antidepressants are efficacious in the treatment of depression and vasomotor symptoms in symptomatic, midlife women. The identification of individuals whom might be at a higher risk for depression during menopausal transition could guide preventive strategies for this population.     

Compounded or confused? Bioidentical hormones and menopausal health

The aim of this article is to focus on compounded bioidentical hormone (BH) formulations for menopausal symptoms and to discuss the impact of these on women's choice of treatment. The practice of compounding BHs for individualized treatment of women with menopausal symptoms has developed in the USA. In spite of claims of superiority, there is no evidence to suggest that these formulations are any more efficacious or safe than conventional hormone replacement therapy (HRT). In fact, there are some concerns about dosing inconsistencies and usefulness of saliva testing that is carried out as part of this type of treatment. While there should be no serious safety issues for women, there is a mismatch between the reality of compounded BH formulations and women's perception of them.     

Breaking Down or Breaking Through

Abstract

Case studies of ten Hong Kong women diagnosed with depression demonstrate that depression is not necessarily, but can be, one strategy for dealing with the problems of everyday life. Neither is it always an outspoken critique of the family as an institution and the gender inequality in the Hong Kong society. However, depression should never be understood simply as personal or social pathology, but as an attempt to negotiate with social reality. These women used their bodies for experiencing, interpreting, and communicating about emotions and social issues. Depression is one of the strategies these women used to resist social forces and transform them into conditions that made possible the creation of space for personal changes.     

The astronaut's wife. Lessons of growth through spousal depression

1. Living with cyclical spousal depression presents both challenges and opportunities for personal growth. 2. Denial can be a significant barrier to the treatment of depression. 3. Spouses of chronically depressed individuals also are at risk for depression. A preventive family-centered approach should be used.     

College Women's Gynecological Health Care Practices and Preferences

Abstract

Panic disorder is characterized by recurrent, sudden, often unprovoked attacks of intense, diffuse autonomic discharge accompanied by severe anxiety as distinguished from ordinary generalized anxiety. Recent research indicates a biochemical abnormality that predisposes some individuals to the disorder, which generally begins in young adulthood and affects women twice as frequently as men. Untreated panic disorder follows a chronic, fluctuating course. Complications include hypochondriasis, anticipatory anxiety, phobic avoidance and agoraphobia, abuse of alcohol and sedative drugs, and depression.

Diagnosis is complicated by patients' complaints of physical rather than emotional symptoms. Workups can be avoided if the physician considers the diagnosis in apparently healthy young adults who present with episodic cardiac, gastrointestinal, neurologic, and/or respiratory symptoms. The physician needs to be able to distinguish the symptoms of panic disorder from those of ordinary anxiety and also to rule out medical conditions that mimic panic disorder.

Neither conventional benzodiazepines nor psychotherapy alone is very effective in stopping panic attacks, but alprazolam, imipramine, and phenelzine are all highly effective. Alprazolam has fewer troublesome side effects, but patience and perseverance are necessary to reach therapeutic levels with all three drugs. Inadequate dosage is the most common cause of treatment failure. Most patients do well once their attacks are controlled and do not require close follow-up. Patient education is an important part of long-term management because relapses are common.     

Thyroid dysfunction in perimenopausal and postmenopausal women

Thyroid dysfunction is common, especially among women over the age of 50. In caring for peri- and post-menopausal women, it is important to recognize the changing clinical manifestations of thyroid disease with age. Postmenopausal women are at increased risk of both osteoporosis and cardiovascular disease, and untreated thyroid disease may exacerbate these risks. Screening for thyroid dysfunction in asymptomatic individuals is controversial, but aggressive case-finding should be pursued, especially in older women. Women with overt thyroid dysfunction should be treated. Therapy for women with subclinical thyroid dysfunction is more controversial, although women with levels of thyroid stimulating hormone (TSH) > or =10 mU/L should be treated, and treatment may be considered in symptomatic women with subclinical hypothyroidism and TSH values <10 mU/L, and in women with subclinical hyperthyroidism who have TSH values consistently <0.1 mU/L. In women who are treated with thyroxine, careful dose titration and monitoring are required in order to prevent the adverse consequences of iatrogenic subclinical hyperthyroidism or hypothyroidism. Finally, caution is required in diagnosing and treating thyroid dysfunction in women who are taking oral estrogens or selective estrogen receptor modulators.     

Acute stress reactions to everyday stressful life events among sexual abuse survivors with PTSD

This study examined symptoms of Acute Stress Disorder (ASD), which is often thought of as a precursor to PTSD, among 54 women who already had PTSD for childhood sexual abuse for which they were seeking treatment. We examined the prevalence of ASD symptoms as well as their relationships to trauma symptoms measured by the Trauma Symptom Checklist-40. The ASD diagnosis requires the occurrence of a traumatic life event as well as meeting specific symptoms criteria. We found that fourty-four percent of participants met all symptom criteria for ASD, but only three of these 24 participants described a traumatic life event. Moreover, ASD symptoms were significantly related to trauma symptom scores. These findings suggest that a significant proportion of women with PTSD for childhood sexual abuse may be highly symptomatic for everyday stressful events that would not be experienced as traumatizing to others. Thus, these individuals need assistance in coping with everyday life stressors that do not involve a serious threat or injury in addition to needing help to alleviate their trauma symptoms.     

Obsessive-compulsive disorder: suffering in silence

Obsessions and compulsions vary in frequency and intensity. Many individuals have habits that cause minimal or no disruption of their lives. OCD, however, causes significant distress and interference with daily life. The problem may go unnoticed by anyone except the involved individual, or it may involve family, friends, and acquaintances. The disorder can be disabling, adversely affecting a student personally, socially, and occupationally. Those who are significantly affected by OC symptoms are encouraged to seek treatment. Behavior therapy and medications are extremely beneficial in helping to relieve symptoms of OCD. Clomipramine and fluoxetine (Prozac) are new drugs available in the US that appear to be effective for OCD symptoms. Several other anti-OCD medications may be available in the US within the next few years. It is important that students and others on campus be made aware that OCD is more common than previously recognized, that more persons with OCD are seeking help, and that effective treatment is available. This "secretive," often disabling disorder is more open now, and it is to be hoped that more individuals will take advantage of current, effective evaluation and treatment modalities.