Provider-patient relationships and trauma among pregnant patients with opioid-use disorder.

BACKGROUND AND OBJECTIVES: The provider-patient relationship is integral to medical practice and health outcomes, particularly among vulnerable patient populations. This study compared the provider-patient relationship among pregnant patients with opioid-use disorder (OUD), who did or did not have a history of moderate to severe trauma. METHODS: This was an exploratory data analysis of 119 patients enrolled in the Support Models for Addiction Related Treatment trial. Probable posttraumatic stress disorder (PTSD) was determined by a score ≥ 31 on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The provider-patient relationship was assessed at 26 ± 4 weeks of pregnancy using the Kim Alliance Scale (KAS). Multivariable regression was used to examine the association of KAS with probable PTSD among pregnant people with OUD. RESULTS: The mean KAS score for pregnant participants without probable PTSD (N = 88) was 61.4 (SD ± 2.8) and for pregnant participants with probable PTSD (N = 31) was 59.6 (SD ± 3.7). Results demonstrated significant differences in KAS scores between those with and without probable PTSD after adjusting for demographic variables. Adjusted mean total KAS scores and scores on Empowerment and Communication subscales were significantly lower among those with probable PTSD compared to those without (p = .04 and 0.02, respectively) but did not differ significantly on Collaboration and Integration subscales. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Analyses show an association between probable PTSD and provider-patient relationship among pregnant patients with OUD, with those with probable PTSD having a worse alliance with obstetric providers. This novel finding helps characterize the provider-patient relationship among a uniquely vulnerable population and can inform efforts to integrate trauma-informed practices into prenatal care.

Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial.

PURPOSE/BACKGROUND: Daily treatment with sertraline improves functional impairment among individuals with premenstrual dysphoric disorder (PMDD). We do not know whether treatment initiated at symptom onset also improves functional impairment. METHODS/PROCEDURES: This 3-site, double blind, randomized, clinical trial compared sertraline (25-100 mg) to similar appearing placebo, both administered at symptom onset, for reduction of PMDD symptoms. Ninety participants were allocated to sertraline and 94 participants to placebo. Functional outcomes from the Daily Ratings of the Severity of Problems included (1) reduced productivity or efficiency at work, school, home, or daily routine; (2) interference with hobbies or social activities; and (3) interference with relationships. Items were measured from 1 (no interference) to 6 (extreme interference) and averaged for the final 5 luteal phase days. This secondary analysis examined whether improvement in functional domains was greater for those allocated to sertraline compared with placebo. Second, we used causal mediation analyses to explore whether specific PMDD symptoms mediated functional improvement. RESULTS/FINDINGS: Only relationship functioning improved significantly with active treatment between baseline and the end of the second cycle (active group mean [SD] change, -1.39 [1.38]; placebo group mean change, -0.76 [1.20]; ß = -0.40; SE, 0.15; P = 0.009). The total effect of treatment on interference was -0.37 (95% confidence interval [CI], -0.66 to -0.09; P = 0.011). Given the nonsignificant direct effect (0.11; 95% CI, -0.07 to 0.29; P = 0.24) and significant indirect effect (-0.48; 95% CI, -0.71 to -0.24; P < 0.001), amelioration of anger/irritability likely mediated reductions in relationship interference. IMPLICATIONS/CONCLUSIONS: That anger/irritability mediates impairments in relationship functioning has face validity but should be replicated in other data sets. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00536198 .

Substance Use Disorder Detection Rates Among Providers of General Medical Inpatients.

BACKGROUND: The prevalence of substance use disorders is higher among medical inpatients than in the general population, placing inpatient providers in a prime position to detect these patients and intervene. OBJECTIVE: To assess provider detection rates of substance use disorders among medical inpatients and to identify patient characteristics associated with detection. DESIGN: Data drawn from a cluster randomized controlled trial that tested the effectiveness of three distinct implementation strategies for providers to screen patients for substance use disorders and deliver a brief intervention (Clinical Trials.gov : NCT01825057). PARTICIPANTS: A total of 1076 patients receiving care from 13 general medical inpatient units in a large teaching hospital participated in this study. MAIN MEASURES: Data sources included patient self-reported questionnaires, a diagnostic interview for substance use disorders, and patient medical records. Provider detection was determined by diagnoses documented in medical records. KEY RESULTS: Provider detection rates were highest for nicotine use disorder (72.2%) and lowest for cannabis use disorder (26.4%). Detection of alcohol use disorder was more likely among male compared to female patients (OR (95% CI) = 4.0 (1.9, 4.8)). When compared to White patients, alcohol (OR (95% CI) = 0.4 (0.2, 0.6)) and opioid (OR (95% CI) = 0.2 (0.1, 0.7)) use disorders were less likely to be detected among Black patients, while alcohol (OR (95% CI) = 0.3 (0.0, 2.0)) and cocaine (OR (95% CI) = 0.3 (0.1, 0.9)) use disorders were less likely to be detected among Hispanic patients. Providers were more likely to detect nicotine, alcohol, opioid, and other drug use disorders among patients with higher addiction severity (OR (95% CI) = 1.20 (1.08-1.34), 1.62 (1.48, 1.78), 1.46 (1.07, 1.98), 1.38 (1.00, 1.90), respectively). CONCLUSIONS: Findings indicate patient characteristics, including gender, race, and addiction severity impact rates of provider detection. Instituting formal screening for all substances may increase provider detection and inform treatment decisions.

Implementing Motivational Interviewing for Substance Misuse on Medical Inpatient Units: a Randomized Controlled Trial.

BACKGROUND: General medical hospitals provide care for a disproportionate share of patients who misuse substances. Hospitalization provides a unique opportunity to identify and motivate patients to address their substance misuse. OBJECTIVE: To determine the effectiveness of three strategies for implementing motivational interviewing for substance misuse with general medical inpatients. DESIGN: Type 3 hybrid effectiveness-implementation randomized controlled trial (Clinical Trials.gov: NCT01825057). PARTICIPANTS: Thirty-eight providers (physicians, physician assistants, nurses) from 13 general medical inpatient services, and 1173 of their patients admitted to an academically affiliated acute care hospital. INTERVENTIONS: Implementation strategies included (1) a continuing medical education workshop on detection of substance misuse and provision of a motivational interview; (2) workshop plus bedside supervision (apprenticeship condition); and (3) a workshop plus ability to place a medical order for an interview from a consultation-liaison service (consult condition). MAIN MEASURES: Primary outcomes were the percentage of study-eligible patients who received an interview for substance misuse and the integrity (adherence, competence) of the interviews. The secondary outcome was the percent of patient statements within the interviews that indicated motivation for reducing substance misuse. KEY RESULTS: 20.5% of patients in the consult condition received an interview, compared to 0.8% (Hedge's g = 1.49) and 3.0% (Hedge's g = 1.26) in the respective workshop only and apprenticeship conditions (p < 0.001). Motivational interviews in the consult condition were performed with more fundamental motivational interviewing adherence and competence than the other conditions. Most statements made by patients during the interviews favored reducing substance misuse, with no differences between conditions. CONCLUSIONS: Providers' ability to place an order to have experts from the consultation-liaison service deliver a motivational interview was a more effective implementation strategy than a workshop or apprenticeship method for ensuring motivational interviewing is available to medical inpatients who misuse substances. TRIAL REGISTRY: NCT01825057.

Premenstrual disorders.

Premenstrual disorders include premenstrual syndrome, premenstrual dysphoric disorder, and premenstrual worsening of another medical condition. While the underlying causes of these conditions continue to be explored, an aberrant response to hormonal fluctuations that occurs with the natural menstrual cycle and serotonin deficits have both been implicated. A careful medical history and daily symptom monitoring across 2 menstrual cycles is important in establishing a diagnosis. Many treatments have been evaluated for the management of premenstrual disorders. The most efficacious treatments for premenstrual syndrome and premenstrual dysphoric disorder include serotonin reuptake inhibitors and contraceptives with shortened to no hormone-free interval. Women who do not respond to these and other interventions may benefit from gonadotropin-releasing hormone agonist treatment.

A randomized controlled trial of screening and brief interventions for substance misuse in reproductive health.

BACKGROUND: Screening, brief intervention, and referral to treatment may reduce substance misuse but has received minimal study among women who are treated in reproductive health settings. OBJECTIVE: The purpose of this study was to determine whether "screening, brief intervention and referral to treatment" that is delivered either electronically or by clinician are more effective than enhanced usual care in decreasing days of primary substance use. STUDY DESIGN: Women from 2 reproductive centers who smoked cigarettes or misused alcohol, illicit drugs, or prescription medication were allocated randomly to "screening, brief intervention and referral to treatment" delivered electronically or by clinician or to enhanced usual care. Assessments were completed at baseline and at 1-, 3-, and 6-months after a baseline has been established. Coprimary outcomes were days/months of primary substance use and postintervention treatment use. A sample size of 660 women was planned; randomization was stratified by primary substance use and pregnancy status. "Screening, brief intervention and referral to treatment" groups were compared with enhanced usual care groups with the use of generalized estimation equations, and effect sizes were calculated with the use of Cohen's d. RESULTS: Between September 2011 and January 2015, women were assigned randomly to a group: 143 women (16.8% pregnant) in the electronic-delivered "screening, brief intervention and referral to treatment" group, 145 women (18.6% pregnant) in the clinician-delivered "screening, brief intervention and referral to treatment" group, and 151 women (19.2% pregnant) in the enhanced usual care group; the retention was >84%. Based on the generalized estimating equations model, predicted mean days per month of use at baseline for primary substance were 23.9 days (95% confidence interval, 22.4-25.5) for the electronic-delivered group, 22.8 days (95% confidence interval, 21.4-24.3) for the clinician-delivered group, and 23.5 days (95% confidence interval, 22.2, 24.9) for enhanced usual care, which respectively declined to 20.5 days (95% confidence interval, 19.0-22.2), 19.8 days (95% confidence interval,18.5-21.3), and 21.9 days (95% confidence interval, 20.7-23.1) at 1 month; 16.9 days (95% confidence interval, 15.0-19.0), 16.6 days (95% confidence interval, 14.8-18.6), and 19.5 days (95% confidence interval, 18.1-21.1) at 3 months; and 16.3 days (95% confidence interval, 14.3-18.7), 16.3 days (95% confidence interval, 14.4-18.5), and 17.9 days (95% confidence interval, 16.1-19.9) at 6 months. Estimated declines were greater in the electronic-delivered group (ß [standard error]=-0.090[0.034]; P=.008; Cohen's d, 0.19 at 1 month, 0.30 at 3 months, and 0.17 at 6 months) and the clinician-delivered group (ß [standard error]=-0.078[0.037]; P=.038; Cohen's d, 0.17 at 1 month, 0.22 at 3 months, and 0.06 at 6 months) compared with enhanced usual care. Treatment use did not differ between groups. CONCLUSION: "Screening, brief intervention and referral to treatment" significantly decreased days of primary substance use among women in reproductive healthcare centers; neither resulted in more treatment use than enhanced usual care.

Postpartum Contraceptive use and Rapid Repeat Pregnancy Among Women who use Substances.

BACKGROUND: Postpartum contraception is especially important for women who use alcohol and other substances, given the risk of possible rapid repeat pregnancy and prenatal substance exposure. However, little is known about postpartum contraceptive use among women with substance use histories. OBJECTIVE: To characterize postpartum contraceptive initiation, 24-month continuation, and rapid repeat pregnancy among women who used substances during pregnancy. METHODS: This is a secondary analysis of 161 pregnant women who enrolled in a randomized clinical trial to treat substance use in pregnancy and completed at least one follow-up assessment. Women were eligible if they were less than 28 weeks gestation and reported alcohol or illicit drug use within the past 30 days. Participants were recruited from two hospital-based OB/GYN clinics between 2006 and 2010, and completed assessments at delivery and 3-, 12-, and 24-months postpartum. RESULTS: Past 30-day use of any substance (not including tobacco) was 52.4%, 58.3%, and 59.8% at 3-, 12-, and 24-month follow-up, respectively. Marijuana was the most commonly reported illicit substance (as high as 48.1%). Rates of any contraceptive use were 71.3%, 66.7% and 65.3% at 3-, 12-, and 24-month follow-up, respectively; DepoProvera and condoms were the most common methods. Rapid repeat pregnancy occurred in 28% of participants by 24-month follow-up. Conclusions/Importance: Postpartum contraceptive use among substance using women was at or near 70%, which is comparable to other samples of postpartum women. Innovative efforts are needed to promote effective contraceptive use among postpartum women in general and among those who use substances in particular.

CDC Grand Rounds: Public Health Strategies to Prevent Neonatal Abstinence Syndrome.

Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome that most commonly occurs in infants after in utero exposure to opioids, although other substances have also been associated with the syndrome (1). NAS usually appears within 48-72 hours of birth with a constellation of clinical signs, including central nervous system irritability (e.g., tremors), gastrointestinal dysfunction (e.g., feeding difficulties), and temperature instability (1) (Box 1). Opioid exposure during pregnancy might result from clinician-approved use of prescription opioids for pain relief; misuse or abuse of prescription opioids; illicit use (e.g., heroin); or medication-assisted treatment (MAT) of opioid use disorder (2) (Box 2).

Economic evaluation of a behavioral intervention versus brief advice for substance use treatment in pregnant women: results from a randomized controlled trial.

BACKGROUND: Substance use in pregnancy is associated with severe maternal and fetal morbidities and substantial economic costs. However, few studies have evaluated the cost-effectiveness of substance use treatment programs in pregnant women. The purpose of this study was to evaluate the economic impact of a behavioral intervention that integrated motivational enhancement therapy with cognitive behavioral therapy (MET-CBT) for treatment of substance use in pregnancy, in comparison with brief advice. METHODS: We conducted an economic evaluation alongside a clinical trial by collecting data on resource utilization and performing a cost minimization analysis as MET-CBT and brief advice had similar effects on clinical outcomes (e.g., alcohol and drug use and birth outcomes). Costs were estimated from the health care system's perspective and included intervention costs, hospital facility costs, physician fees, and costs of psychotropic medications from the date of intake assessment until 3-month postpartum. We compared effects of MET-CBT on costs with those of brief advice using Wilcoxon rank sum tests. RESULTS: Although the integrated MET-CBT therapy had higher intervention cost than brief advice (median = $1297/participant versus $303/participant, p < 0.01), costs of care during the prenatal period, delivery, and postpartum period, as well as for psychotropic medications, were comparable between the two groups (all p values ≥ 0.55). There was no statistically significant difference in overall cost of care (median total cost = $26,993/participant for MET-CBT versus $27,831/participant for brief advice, p = 0.90). CONCLUSIONS: The MET-CBT therapy and brief advice resulted in similar clinical outcomes and overall medical costs. Further research incorporating non-medical costs, targeting women with more severe substance use disorders, and evaluating the impact of MET-CBT on participants' quality of life will provide additional insights. TRIAL REGISTRATION: ClinicalTrials.gov NCT00227903 . Registered 27 September 2005.

The role of screening, brief intervention, and referral to treatment in the perinatal period.

Substance use during pregnancy is at least as common as many of the medical conditions screened for and managed during pregnancy. While harmful and costly, it is often ignored or managed poorly. Screening, brief intervention, and referral to treatment is an evidence-based approach to manage substance use. In September 2012, the US Centers for Disease Control and Prevention convened an Expert Meeting on Perinatal Illicit Drug Abuse to help address key issues around drug use in pregnancy in the United States. This article reflects the formal conclusions of the expert panel that discussed the use of screening, brief intervention, and referral to treatment during pregnancy. Screening for substance use during pregnancy should be universal. It allows stratification of women into zones of risk given their pattern of use. Low-risk women should receive brief advice, those classified as moderate risk should receive a brief intervention, whereas those who are high risk need referral to specialty care. A brief intervention is a patient-centered form of counseling using the principles of motivational interviewing. Screening, brief intervention, and referral to treatment has the potential to reduce the burden of substance use in pregnancy and should be integrated into prenatal care.

Early Childhood Adversity and Pregnancy Outcomes.

OBJECTIVES: To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. METHODS: Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. RESULTS: Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. CONCLUSIONS: ACEs have an enduring effect on maternal reproductive health, as manifested by mothers' delivery of offspring that were of reduced birth weight and shorter gestational age.

Clinical correlates of prescription opioid analgesic use in pregnancy.

A 2012 committee opinion from the American College of Obstetricians and Gynecologists highlights the considerable increase in opioid addiction in recent years, yet little is known about clinical correlates of prescribed opioids among pregnant women. This study examines clinical and demographic factors associated with the use of opioid analgesics in pregnancy. Data were derived from a prospective cohort study of pregnant women. Participants were administered the Composite International Diagnostic Interview to identify depressive and anxiety disorders and data on medication use were gathered at three assessment points and classified according to the Anatomical Therapeutic Chemical Code (ATC) classification system ATC group N02A. Participants included 2,748 English or Spanish speaking pregnant women. Six percent (n = 165) of women used opioid analgesics at any point in pregnancy. More pregnant women using opioids met diagnostic criteria for major depressive disorder (16 vs. 8 % for non users), generalized anxiety disorder (18 vs. 9 % for non users), post-traumatic stress disorder (11 vs. 4 % for non users) and panic disorder (6 vs. 4 % for non users). Women who reported opioid use were also significantly more likely than non users to report using illicit drugs and almost three times as likely to report smoking cigarettes in the second or third trimester of pregnancy (4 and 23 %, respectively) as compared to non-opioid users (0.5 and 8 %). The use of opioids in pregnancy was associated with higher levels of psychiatric comorbidity and use of other substances as compared to non-opioid users.

Antidepressant use in pregnant and postpartum women.

Women in their reproductive years are at risk of experiencing depressive and anxiety disorders. As such, it is likely that pregnant women will undergo treatment with antidepressants. We review the risk of adverse birth outcomes and neonatal complications subsequent to antidepressant use in pregnancy. An inconsistent literature shows that antidepressant exposure is associated with shortened gestations and diminished fetal growth; these effects are small. Transitory neonatal signs are seen in some neonates after exposure to antidepressants in utero. No specific pattern of malformations has been consistently associated with antidepressants, with the possible exception of paroxetine and cardiac malformations. There is inconclusive evidence of a link between antidepressants in late pregnancy and persistent pulmonary hypertension in the newborn. Extensive study finds that antidepressants cannot be considered major teratogens. It is likely that confounding factors contribute to a number of the adverse effects found to be associated with antidepressant use in pregnancy.

Reporting Perinatal Substance Use to Child Protective Services: Obstetric Provider Perspectives on the Impact on Care.

Objective: To understand obstetric provider perspectives on child protective services (CPS)-mandated reporting requirements and how they affect care for pregnant and postpartum patients with opioid use disorder (OUD). Methods: Key informant interviews were conducted virtually with obstetricians, nurse practitioners, and social workers caring for obstetric patients (n = 12). Providers were asked about their experience as mandated reporters working with patients with OUD. Transcripts were independently coded by two staff, and content analysis was used to identify themes. Results: Our analysis resulted in six thematic areas, including CPS-mandated strengths, concerns related to CPS reporting requirements, implementation of mandates, supporting patients after CPS report, communication between stakeholders, and the impact on care. Providers noted that the fear of CPS involvement causes some patients to delay or not engage in care. Other patients are hesitant to accept medications for OUD for fear of CPS involvement. The inconsistencies in how reporting mandates are applied and how CPS handles cases make communication about the policies challenging for providers and create anxiety for patients. Conclusions: The results of this study indicate that mandated reporting requirements and the potential for CPS involvement are perceived to have minimal positive effects on perinatal individuals with OUD and may negatively affect patients and their care. Clinicaltrials.gov number: NCT04240392.

Formative evaluation of an emergency department clinical decision support system for agitation symptoms: a study protocol.

INTRODUCTION: The burden of mental health-related visits to emergency departments (EDs) is growing, and agitation episodes are prevalent with such visits. Best practice guidance from experts recommends early assessment of at-risk populations and pre-emptive intervention using de-escalation techniques to prevent agitation. Time pressure, fluctuating work demands, and other systems-related factors pose challenges to efficient decision-making and adoption of best practice recommendations during an unfolding behavioural crisis. As such, we propose to design, develop and evaluate a computerised clinical decision support (CDS) system, Early Detection and Treatment to Reduce Events with Agitation Tool (ED-TREAT). We aim to identify patients at risk of agitation and guide ED clinicians through appropriate risk assessment and timely interventions to prevent agitation with a goal of minimising restraint use and improving patient experience and outcomes. METHODS AND ANALYSIS: This study describes the formative evaluation of the health record embedded CDS tool. Under aim 1, the study will collect qualitative data to design and develop ED-TREAT using a contextual design approach and an iterative user-centred design process. Participants will include potential CDS users, that is, ED physicians, nurses, technicians, as well as patients with lived experience of restraint use for behavioural crisis management during an ED visit. We will use purposive sampling to ensure the full spectrum of perspectives until we reach thematic saturation. Next, under aim 2, the study will conduct a pilot, randomised controlled trial of ED-TREAT at two adult ED sites in a regional health system in the Northeast USA to evaluate the feasibility, fidelity and bedside acceptability of ED-TREAT. We aim to recruit a total of at least 26 eligible subjects under the pilot trial. ETHICS AND DISSEMINATION: Ethical approval by the Yale University Human Investigation Committee was obtained in 2021 (HIC# 2000030893 and 2000030906). All participants will provide informed verbal consent prior to being enrolled in the study. Results will be disseminated through publications in open-access, peer-reviewed journals, via scientific presentations or through direct email notifications. TRIAL REGISTRATION NUMBER: NCT04959279; Pre-results.

A pilot study to compare fluoxetine, calcium, and placebo in the treatment of premenstrual syndrome.

Serotonin reuptake inhibitors and calcium supplements ameliorate symptoms of premenstrual syndrome. A comparison of these agents to placebo may guide treatment selection. The goal of this pilot study was to compare fluoxetine and calcium to placebo.We enrolled 39 women with at least 3 moderate to severe premenstrual symptoms and functional impairment. The trial compared fluoxetine (10 mg twice daily), calcium carbonate (600 mg twice daily), and placebo over the course of 4 menstrual cycles. The Inventory of Depressive Symptomatology, Premenstrual Tension Scale, Clinical Global Impression-Severity and -Improvement scales, and Daily Record of Severity of Problems were used to measure symptoms.Symptom improvement was greatest for the fluoxetine group, although significance was achieved only for the Daily Record of Severity of Problems (ß = -0.28; 95% confidence interval, -1.70 to -0.35; P = 0.02) and the Clinical Global Impression-Improvement (ß = -1.03; 95% confidence interval= -1.70 to -0.35; P = 0.04). The Cohen d effect sizes for fluoxetine relative to placebo were between 0.80 and 2.08, whereas the effect sizes for calcium were only between 0.10 and 0.44.Fluoxetine had clear therapeutic benefit for premenstrual syndrome, whereas the effect of calcium was much smaller. Results of this pilot do not support the need for a larger study that would compare these compounds.

ISPMD consensus on the management of premenstrual disorders.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.