By O. Delazar. University of North Dakota--Lake Region.
Individual agents T-20 (Enfuvirtide purchase lyrica overnight delivery, Fuzeon) is the prototype of the fusion inhibitors cheap generic lyrica uk. T-20 was licensed in Europe and the US in May 2003 for the treatment of HIV-1 infection in antiretroviral-experienced adults and children over 6 years of age proven 75mg lyrica. It is a relatively large peptide comprised of 36 amino acids, and therefore needs to be administered by subcutaneous injection. It binds to an intermediate structure of the HIV gp41 protein, which appears during fusion of HIV with the target cell. Antiviral activ- ity was dose-dependent, and at the higher dose of 100 mg BID, the viral load was reduced by almost 2 logs (Kilby 1998+2002). In early studies of the subcutaneous application, an effect on viral load was still evident in one third of patients after 48 weeks. TORO 1 (T-20 versus Optimized Regimen Only) enrolled 491 extensively pretreated patients in North America and Brazil, most with multiresistant viruses. In TORO 2, 504 patients in Europe and Australia were enrolled. Patients in both studies on an optimized ART regimen either received 90 mg T-20 BID subcutaneously or none at all (Lalezari 2003, Lazzarin 2003). A strong impact on viral load was also seen with tipranavir, darunavir, maraviroc or raltegravir. In all large studies evaluating these agents (RESIST, POWER, MOTIVATE, BENCHMRK), the additional use of T-20 was of significant benefit. If at least two active substances are not available, the option of T-20 should be discussed with the patient. Small pilot studies such as INTENSE or INDEED suggest that T-20, given as “induction”, i. The success of T-20 therapy should be monitored early on, particularly in view of the cost. Patients without a decrease in viral load of at least one log after 8-12 weeks will not benefit and can be spared the required twice-daily injections. It is also not recommended to inject the full daily dose of T-20 once a day: although 180 mg QD has the same bioequivalence (as measured by AUC) to the standard 90 mg BID, at least one study has shown a trend towards a smaller decrease in viral load with the QD dose that was clearly associated with lower trough levels (Thompson 2006). One observation in the TORO studies was the increased frequency of lym- phadenopathy and bacterial pneumonia in those on T-20 (6. Septicemia also occurred more often on T-20, but the difference was not significant. The reason for the increased rate of infections remains unclear, but binding of T-20 to granulocytes has been suspected. Substantial side effects remain constant (98% in the TORO studies), and over the course of therapy, severe local skin reactions occur at the injection site. These can be particularly painful and can result in interruption of therapy: 4. In our experience of everyday clinical treatment, therapy is interrupted frequently due to these skin problems (see section on Side Effects). Unfortunately the development of a bio-injection system in which T-20 is pressed into the skin was halted. Resistance mutations develop relatively rapidly on T-20, but seem to reduce viral fitness (Lu 2002, Menzo 2004). Receptor tropism of the virus seems to be not significantly affected. There are some changes to a short sequence on the gp41 gene, causing reduced susceptibility to T-20, which is due to simple point mutations (Mink 2005). In contrast, viruses resistant to NRTIs, NNRTIs and PIs are susceptible to T-20 (Greenberg 2003). As it is a relatively large peptide, it induces antibody production. This does not seem to impair efficacy (Walmsley 2003). More disturbing is the fact that in a large TDM study there was a very large interpatient variability and extremely low plasma levels were often found (Stocker 2006). In summary, patients with a well-controlled viral load or who still have options with classical ART do not require T-20. For salvage therapy the drug seems to be very valuable in individual cases. However, T-20 probably has only a minor role to play in the future of HIV treatment. Many patients have already successfully replaced T-20 with newer oral antiretrovirals like raltegravir (DeCastro 2009, Grant 2009, Santos 2009, Talbot 2009, Gallien 2011). Overview of antiretroviral agents 115 Increasing efficacy of ART and/or emptying latent reservoirs with T-20, as first reports suggested (Lehrmann 2005, Molto 2006), seem unlikely now (Gandhi 2010, Morant- Joubert 2012). The price also remains significant – ART costs can skyrocket with the addition of T-20, the sponsor maintaining that it is one of the most complicated drugs it has ever manufactured. References Clotet B, Capetti A, Soto-Ramirez LE, et al. A randomized, controlled study evaluating an induction treatment strategy in which enfuvirtide was added to an oral, highly active antiretroviral therapy regimen in treatment- experienced patients: the INTENSE study. Switch from enfuvirtide to raltegravir in virologically suppressed mul- tidrug-resistant HIV-1-infected patients: a randomized open-label trial. No evidence for decay of the latent reservoir in HIV-1-infected patients receiv- ing intensive enfuvirtide-containing antiretroviral therapy. Switch from enfuvirtide to raltegravir in Virologically suppressed HIV-1 infected patients: effects on level of residual viremia and quality of life. Baseline and on-treatment susceptibility to enfuvirtide seen in TORO 1 and 2 to 24 weeks. AbstractID=1687 Kilby JM, Hopkins S, Venetta TM, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study.
If pregnancy is likely discount lyrica online, you length and it does not account for leap years discount lyrica 150 mg with visa. If you may confirm this by taking a urine pregnancy test want to be correct lyrica 150mg with amex, you have to use a calendar. Exact (UPT) or, even better, an ultrasound if available at 280 days past LMP is found by checking the day of your facility. Only perform a UPT if you are in the week of the LMP and adjusting the calculated date doubt of possible pregnancy. This could save costs to land on the same day of the week. The calculated date (15 February) is a After confirmation of her pregnancy, try to assess Friday; adjusting to the closest Tuesday produces 12 the duration (or gestational age) of the pregnancy. This can be obtained by verifying the first day of her last menstrual period. With the LMP and Naegele’s rule one can estimate All these questions can give insight in the severity the expected date of delivery (EDD) and deduce of the case. A woman who suffered from bleeding the gestational age of the pregnancy (Box 1). If the which started before pregnancy might have cervical woman does not know the exact LMP, try to make or vaginal lacerations due to multiple reasons. A a reasonable estimate of the gestational age in woman with acute bleeding, who has to change weeks. Naegele’s rule assumes an average cycle her underwear frequently and suffers from accom- length of 28 days, which is not true for everyone. Nowadays Do not forget to check for other accompanying there are several online calculators as well, e. After assessing the gestational age of the patient’s • Provoked bleeding Is the bleeding spontaneous or pregnancy, you should explore her complaint. This could indi- Suggested questions for assessment of the vaginal cate a cervical origin of the problem, e. Did it start Do ask for other accompanying symptoms: acutely or gradually? Was it already present be- • Abdominal cramping pain: acute, continuous, fore pregnancy? Also try to estimate the amount localized or general. Be aware though, as an ectopic preg- • Did she lose any tissue vaginally? This might nancy can present with little loss of blood. This could present with lacerations and It could also be a symptom of an infection which STI. Sometimes a urinary tract infection cal bleeding, ectopic pregnancy and miscarriage. Painless macro- hematuria is a sign for urinary schistosomiasis. This could point towards You should be aware that the patient might be sexually transmitted infection (STI) such as concerned about losing her pregnancy and there- gonorrhea. Chlamydia classically presents with fore she could be emotional. Pay special attention painless bleeding or bleeding after intercourse. She might have had an earlier treat- sure, temperature and pulse rate. An • Risk of criminal abortion Did the woman try to ectopic pregnancy can reoccur. Sometimes women do not dare to N Fundal height to assess the gestational age. More likely in (and most of the times septic) abortion. Then consider STI, pelvic abscesses or non- Assess her past medical history: gynecological causes of peritonitis (see • Obstetric history Is this her first pregnancy? Some drugs are known gynecological tumors (see Chapter 12 on to increase the risk of miscarriage, e. You might want to originates from the cervix, vagina or the uterine check your pharmaceutical reference guides for cavity. Sometimes the cervix is very friable in possible association between drugs and mis- pregnancy. Toxins such as lead, mercury, formal- speculum, it starts to bleed. Be sure to perform the vaginal • Did she have any operations in the past? An examination carefully in cases where you suspect ectopic pregnancy due to pelvic inflammatory an ectopic pregnancy. HIV infection is also a risk factor for that cervical evaluation is not reliable in dis- developing cervical carcinoma and these patients tinguishing between complete and incom- may have had other STIs. Sometimes products of 23 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS conception are still present in the ostium of leukocyte count are both slightly elevated in the cervix and can be removed during digital pregnancy. If the ostium is closed, Urine: this could indicate a threatening miscarriage, • UPT: urine pregnancy test to confirm preg- missed abortion or ectopic pregnancy. This could indicate an infection or ectopic pregnancy. Make sure you explain to the N Assess for foreign bodies. If no blood is found on digital and visual vaginal examination, perform an inspection Direct light microscopy: of the entire genital area. Sometimes patients have diffi- is not responding to standard treatment. Schisto- culties assessing the origin of the blood loss soma in the urine may indicate (concomitant) themselves, especially in rural areas where no genital tract schistosomiasis but can be false proper sanitary facilities are present. If your facility has an ultrasound machine, every patient with first-trimester bleeding Other investigations should receive an ultrasound investigation to estab- lish a viable intrauterine pregnancy. Rule of thumb Ultrasound for referral is: if a patient (who has not been labelled Chapter 1 on gynecological examination presents as having a serious, possibly life-threatening, condi- detailed information on how to perform an tion which calls for imminent referral) presents ultrasound. However, the diagnosis Laboratory investigations depends on the quality of the ultrasound equip- ment, the experience of the sonographer, the speci- It should be noted that most of the causes of vaginal fic signs and symptoms of the patient and presence bleeding in the first trimester can be identified after of physical factors such as fibroids. The first two thorough history taking and physical examination. Additional laboratory investigations hardly contri- So, beware, a pregnant patient with peritoneal pain bute to the diagnosis. Blood: If no intrauterine pregnancy is visible on ultra- • Hemoglobin and cross-matching in case of sound, check for adnexal masses or clear ectopic severe bleeding or suspected ectopic pregnancy.
Atypical antipsychotics are associated with lower rates of the development of this neurological side effect in comparison with the older purchase genuine lyrica line, conventional agents buy lyrica 150 mg on line. Atypical antipsychotics may also treat negative symptoms and improve cognitive functioning order 75mg lyrica with visa. Table 1 describes drug indications approved by the US Food and Drug Administration, dosing, and mechanisms of action based on the current product labels for the 10 atypical antipsychotics available in the United States and Canada. Clozapine, the prototypic atypical antipsychotic, was introduced in 1989. Since then, 9 other atypical antipsychotics have been brought to market: risperidone (1993), risperidone long-acting injection (2003), olanzapine (1996), quetiapine (1997), ziprasidone (2001), aripiprazole (2002), extended-release paliperidone (2006), asenapine (2009), iloperidone (2009), and paliperidone long-acting injection (2009). Atypical antipsychotics vary from one another in receptor interaction selection and affinity. These differences in receptor activity are hypothesized to account for differences in efficacy, safety, and tolerability among atypical antipsychotics, as well as in comparison with conventional antipsychotics. Clozapine is an antagonist at dopamine (D1-5) receptors with relatively low affinity for D and D receptors and high affinity for D receptors. Its greater1 2 4 activity at limbic (opposed to striatal) dopamine receptors and lower affinity for D receptors2 may explain the low incidence of extrapyramidal side effects. The antipsychotic effect of risperidone, olanzapine, quetiapine, and ziprasidone is proposed to be primarily via D and serotonin (5-HT ) receptor antagonism. However, each drug2 2 has varying effects on these and other receptors (see Table 1). Antagonism of the 5-HT2 receptors is thought to reduce the extent of D receptor antagonism in the striatum and cortex2 while leaving blockade of D receptors in the limbic area unaffected. These properties are2 thought to account for fewer extrapyramidal side effects and better effects on the negative symptoms of schizophrenia compared with conventional antipsychotics. However, in doses higher than 6 mg daily, the profile for risperidone may become more similar to a conventional antipsychotic due to increased D receptor blockade. Aripiprazole is a partial agonist at D receptors; thus it is an antagonist in the2 presence of high levels of endogenous dopamine and, conversely, acts as an agonist when minimal dopamine is present. Aripiprazole is also a partial agonist at 5-HT1A receptors that may contribute to improvements in anxiety, depression, negative symptoms, and lower incidence of extrapyramidal side effects. Paliperidone is a major active metabolite of risperidone. While risperidone is subject to drug interactions affecting the CYP2D6 enzyme, in vivo studies suggest this isozyme plays a limited role in the clearance of paliperidone. Paliperidone does not require dose adjustments in mild to moderate hepatic impairment, but awaits studies for use in patients with severe hepatic impairment. Iloperidone is an antagonist at the D and 5-HT receptors. It2 2 targets the 5-HT and histamine H1 receptors, thought to play a role in counteracting6 Atypical antipsychotic drugs Page 12 of 230 Final Report Update 3 Drug Effectiveness Review Project extrapyramidal symptoms, sedation, and weight gain. Efficacy of asenapine is believed be a combination of antagonist activity at the dopamine D and 5-HT2 2A receptors. The variation in receptor interaction among these drugs is thought to lead to differences in symptom response and adverse effects. Product labels state that antagonism of α1-adrenergic receptors may explain the orthostatic hypotension observed with aripiprazole, olanzapine, quetiapine, and ziprasidone. Antagonism of H receptors may explain the somnolence observed1 with olanzapine, quetiapine, and ziprasidone and antagonism of muscarinic M1-5 receptors with olanzapine may explain its anticholinergic effects. However, no specific effects related to symptom response based on receptor interaction profiles are known. Atypical antipsychotic drug indications and mechanisms of action Generic Indications approved by the US Food name Trade name and Drug Administration Pharmacodynamics Schizophrenia in adults and adolescents ® Abilify Tablet (13-17 years) Partial agonist at D2 and 5-HT1A Manic and mixed episodes associated receptors, antagonist at 5-HT2A ® b with bipolar I disorder in adults and receptors Abilify Discmelt ODT pediatric patients (10-17 years) High affinity for D2, D3, 5-HT1A, and Adjunctive treatment to antidepressants 5-HT2A receptors; moderate affinity Aripiprazole for major depressive disorder in adults for D4, 5-HT2C, 5-HT7, - α - ® b and pediatric patients (10-17 years) adrenergic and H1 receptors Abilify Liquid Treatment of irritability associated with Moderate affinity for the serotonin autistic disorder reuptake site and no appreciable affinity for cholinergic muscarinic ® Abilify Intramuscular Agitation associated with schizophrenia or receptors b bipolar disorder, manic or mixed in adults Injection High affinity for serotonin 5-HT1A, Acute treatment of schizophrenia in adults 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5- HT5-7 receptors, dopamine D1-4 ® b Acute treatment of manic or mixed Asenapine Saphris Tablet receptors, α1 and α2-adrenergic episodes associated with bipolar I receptors, and histamine H1 disorder with or without psychotic features receptors in adults Moderate affinity for H2 receptors ® d Treatment-resistant schizophrenia in Antagonist at D1-3,5 receptors, with Clozaril Tablet adults high affinity for D4 receptors. Also c Clozapine Reduction in risk of recurrent suicidal antagonist at serotonergic, ® b behavior in schizophrenia or adrenergic, cholinergic, and Fazaclo ODT histaminergic receptors schizoaffective disorder in adults High affinity to serotonin 5-HT2A and dopamine D2 and D3 receptors b Iloperidone Fanapt™ Tablet Schizophrenia in adults Moderate affinity for dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors Schizophrenia in adults and adolescents Selective monaminergic antagonist ® d Olanzapine Zyprexa Tablet (13-17 years) with high affinity binding to 5- HT2A/2C, 5-HT6, D1-4, histamine H1, Atypical antipsychotic drugs Page 13 of 230 Final Report Update 3 Drug Effectiveness Review Project Generic Indications approved by the US Food name Trade name and Drug Administration Pharmacodynamics Monotherapy or in combination therapy and α1-adrenergic receptors for acute mixed or manic episodes ® ® d associated with bipolar I disorder in adults Zyprexa Zydis ODT and adolescents (13-17 years) Maintenance monotherapy of bipolar I disorder in adults ® Zyprexa Intramuscular Acute agitation associated with Injection schizophrenia or bipolar I mania in adults ® Acute and maintenance treatment of Invega ER Tablet schizophrenia in adults Antagonist at D2 receptors and 5- Mono or adjunctive therapy for HT2A receptors Paliperidone schizoaffective disorder in adults Also antagonist at α1-2 and H1 ® ® Invega Sustenna receptors Acute and maintenance treatment of ER Intramuscular schizophrenia in adults Schizophrenia in adults and adolescents (13-17 years) Acute treatment of manic episodes associated with bipolar I disorder, both as monotherapy and as an adjunct to lithium or divalproex in adults and as ® d monotherapy in pediatric patients (10-17 Seroquel Tablet years) Acute treatment of depressive episodes associated with bipolar disorder in adults Maintenance treatment of bipolar disorder as an adjunct to lithium or divalproex in adults Antagonist at D1-2, 5HT 1A-2A, Quetiapine Acute and maintenance treatment of norepinephrine transporter (NET), schizophrenia in adults H1, M1, and α1b-2, receptors Acute treatment of manic or mixed episodes associated with bipolar I disorder, both as monotherapy and as an adjunct to lithium or divalproex in adults ® Seroquel XR Tablet Acute treatment of depressive episodes associated with bipolar I disorder in adults Maintenance treatment of bipolar I disorder as an adjunct to lithium or divalproex in adults Adjunctive treatment of major depressive disorder in adults ® Acute and maintenance treatment of d Risperdal Tablet, Liquid schizophrenia in adults and acute treatment in adolescents (13-17 years) Monotherapy (for adults and children 10- Antagonist with high affinity d 17 years) or combination therapy (for binding to 5-HT2 and D2 receptors Risperidone adults) for acute mixed or manic episodes Antagonist at H1, and α1-2 ® ® d Risperdal M-TAB ODT associated with bipolar I disorder receptors Treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years Atypical antipsychotic drugs Page 14 of 230 Final Report Update 3 Drug Effectiveness Review Project Generic Indications approved by the US Food name Trade name and Drug Administration Pharmacodynamics ® ® Schizophrenia in adults Risperdal Consta Long-acting Intramuscular Monotherapy or adjunctive therapy to Injection lithium or valproate in adults Schizophrenia in adults Acute mixed or manic episodes ® Geodon Capsule associated with bipolar I disorder in adults Adjunctive therapy for maintenance e treatment of bipolar disorder in adults Antagonist with high affinity Ziprasidone ® Geodon Intramuscular binding to 5-HT2 and D2 receptors b Acute agitation in schizophrenia in adults Injection Schizophrenia in adults ® b Geodon Suspension Acute manic and mixed episodes associated with bipolar disorder in adults Abbreviations: ER, extended release; Max, maximum; ODT, orally disintegrating tablet; XR, extended release. All information in this table is derived from individual product labels. Refer to the product labels for information on dosing. Indications Addressed This review addresses the use of atypical antipsychotics to treat schizophrenia, bipolar disorder, major depressive disorder, behavioral and psychological symptoms of dementia in adults, and pervasive developmental disorders and disruptive behavior disorders in children. Descriptions of these populations are based on the Diagnostic and Statistical Manual of Mental Disorders-Fourth 2 Edition (DSM-IV). It is important to note that patients with severe symptoms of mental illness will often not be included in trials because of their inability or refusal to provide consent, unless the patient is a child and their parent or guardian gives consent. Therefore, clinical trials are generally not a good source of evidence specific to this group of patients. Schizophrenia The essential features of schizophrenia include a constellation of positive and negative symptoms that persist for at least 6 months. Positive symptoms include specific distortions of thought and perception (i. The negative symptom spectrum is characterized by restrictions on emotions, thought processes, speech, and goal-directed behavior. The course of schizophrenia is variable but generally leads to marked impairment in major areas of functioning. Clinical trials have reported that 10% to 20% of individuals with schizophrenia do not 3 significantly benefit from conventional antipsychotic therapy. Subsequently, a large body of research has emerged that focuses specifically on this subgroup of individuals with treatment- resistant schizophrenia. Atypical antipsychotic drugs Page 15 of 230 Final Report Update 3 Drug Effectiveness Review Project Schizoaffective Disorder Mood disturbance distinguishes schizoaffective disorder from schizophrenia. In schizoaffective disorder, a major depressive, manic, or mixed mood episode must be concurrent with positive and negative symptoms characteristic of schizophrenia and must be present for a substantial portion of the duration of illness preceded or followed by at least 2 weeks of delusions or hallucinations without prominent mood symptoms (DSM-IV). The typical age of onset for schizoaffective disorder is early adulthood. The DSM-IV suggests that schizoaffective disorder is less prevalent than schizophrenia, with a prognosis that is somewhat better. Schizoaffective disorder is nevertheless associated with occupational impairment and increased risk of suicide. Schizophreniform Disorder Schizophreniform disorder differs from schizophrenia primarily in duration of illness. Schizophreniform disorder is characterized by a course of positive and negative symptoms that resolve within a 6-month time period or when a person is currently symptomatic less than the 6 months required for a diagnosis of schizophrenia (DSM-IV). Schizophreniform disorder is less prevalent than schizophrenia. The DSM-IV states that the course of schizophreniform disorder persists beyond 6 months in approximately two-thirds of all cases, progressing to a diagnosis of schizophrenia. Bipolar Disorder The course of bipolar disorder is generally chronic and involves 1 or more episodes of mania or mixed mood.
Hyperprolactinemia caused by Polycystic ovary syndrome (PCOS) is present a prolactinoma needs treatment if a woman wants when two out of three criteria are present: oligo- to conceive order lyrica 150 mg. Bromocriptine 150mg lyrica visa, a dopamine agonist buy lyrica 150 mg mastercard, amenorrhea, signs of hyperandrogenism (hirsutism, 2. Vaginal surgery obesity is not part of the criteria, many women for congenital anomalies. Clin Obst Gynaecol 2010;53: 115–24 with PCOS are overweight or obese. Treatment of tuberculosis: an intra-ovarian environment that is not conducive Guidelines, 4th edn. Geneva: WHO, 2010 for development of a dominant follicle. Genital tuber- with this syndrome respond with a withdrawal culosis: an important cause of Asherman’s syndrome in bleeding when given norethisterone because their India. Asherman syn- endometrium has been stimulated by estrogens. Obstet Gynecol 1995; This unopposed endometrial stimulation might be 85:8–9 a risk factor for endometrial cancer and in women 10. J Obstet with no wish to conceive, the oral contraceptive Gynecol 2007;27:55–9 pill should be advised. Sheehan’s syn- also has a positive effect on hirsutism when used for drome in a developing country, Nigeria: a rare disease 9 months or longer. Am J Med Sci 2010;340:402–6 used for women who wish to conceive: start with 13. Epidemiologic 50mg daily for 5 days to be increased to maximally aspects of postpartum pituitary hypofunction (Sheehan’s 150mg daily for 5 days (see Chapter 16 on syndrome). Delayed puberty: experience of a tertiary care centre in REFERENCES India. The Practice Committee of the American Society of Best Pract Res Clin Endocrinol Metab 2002;16:73–90 Reproductive Medicine. Fertil Steril 2008;90:S19–25 Consensus Workshop Group. Deligeoroglou E, Athanasopoulos N, Tsimaris P, et al. Fertil Steril 2004;81: Ann NY Acad Sci 2010;1205:23–32 19–25 3. International variability of ages at menarche and menopause: patterns Further reading (free e-books) and main determinants. HTM estimates of puberty timing in Senegalese adolescent girls. The prevalence of AUB is estimated at 12% in the general population Chronic abnormal uterine bleeding and increases with age, reaching 24% in those aged 36–40 years. When it is a single episode of irregular Chronic AUB is defined by the International Fed- blood loss in non-pregnant women, it is most of eration of Gynecology and Obstetrics (FIGO) as the time harmless, but it can also be a first sign of bleeding from the uterine corpus that is abnormal serious pathology such as cancer of the cervix. For in volume, regularity, and/or timing, and has been this reason it is important to do a full gynecological present for the majority of the past 6 months in history, a speculum examination and a vaginal non-pregnant women. For practical purposes it is important to rule out Acute abnormal uterine bleeding (unrecognized) pregnancy problems or infection in Acute AUB is defined as an episode of heavy bleed- AUB of short duration. A longer duration of AUB ing in non-pregnant women that, in the opinion of points to more structural abnormalities like fibroids, the clinician, is of sufficient quantity to require im- polyps or malignancies. This chapter will describe the problems and Acute AUB may present in the context of existing how to establish the diagnosis. A flow chart for chronic AUB or might occur without such a history. In Chapter 20 appropriate treatment of abnormal CAUSES OF UTERINE BLEEDING uterine bleeding will be explained. For bleeding after the menopause, please see Chapter 10. FIGO have developed a classification system for AUB (Table 1)2. Definition • Polyps and pendiculated fibroids: (generally) benign growths of uterine muscle (fibroids) or endo- Terms like menorrhagia, metrorrhagia, meno- metrium (polyps). Adenomyosis describes the pres- speak of ‘abnormal uterine bleeding’: ence of endometrial tissue in the myometrium. The main menstrual blood partly related to the absolute presence of endo- flow during a period is 35ml with 65% of metrial tissue in the myometrium and partly due women losing <60ml each period. PALM refers to structural abnormalities causing about 25–40%) and should be treated surgic- the abnormal bleeding, COEIN are non-structural causes ally. When no atypia is present conservative treatment with Mirena intrauterine device P Polyps C Coagulopathy (IUD) or cyclic progestogens (medroxy- A Adenomyosis O Ovulatory dysfunctions progesterone acetate (10mg/day for 12–14 L Leiomyoma E Endometrial days in the luteal phase of the cycle for 3 months), and repeated sampling is justified. M Malignancy or I Iatrogenic N Cervical ectopia or ectropion can cause spot- hyperplasia N Not yet classified ting and postcoital bleeding (often in young women or pill users). N Infections: Sexually transmitted infections (STIs) like chlamydia, urogenital schistoso- miasis or genital tuberculosis. Chapter 28) of the ovaries produce estrogen and N Tricyclic antidepressants like amitriptyline cause endometrial hyperplasia and AUB and may cause AUB. The term ovarian dysfunction HISTORY TAKING (OD) is used when hormonal imbalance is present. Common groups affected by OD are: • Duration of complaints (primary/secondary, N Young girls and perimenopausal women: how many months/years). Primary AUB starts both groups have anovulatory cycles (cycles from the first period, secondary AUB starts later without an ovulation). Cervical cancer is often accompa- menstrual cycle see Chapter 16 on subfertility. In obesity peripheral fat tissue produces estro- • Swelling in the abdomen is a symptom of gen and morbidly obese women have a high fibroids and ovarian masses but also of unrecog- level of estrogen that disturbs the menstrual nized pregnancy. Weight loss and emaceration can lead to • Easy bleeding tendency. Some women have in- anovulatory cycles and cause irregular periods herited bleeding disorders. They often have a • Endometrial causes of AUB are: history of prolonged bleeding during surgery, N A primary disorder of mechanisms regulating trauma or childbirth. It is difficult in low- local endometrial ‘hemostasis’ itself: endo- resource settings to establish the exact diagnosis metrial hemostasis is a very complex process but you can treat heavy periods in these women and local hormonal imbalance in the prosta- the same as in women without bleeding dis- glandin mechanism can cause AUB. Make women with N Endometrial hyperplasia is a precursor to inherited bleeding disorders aware that it is endometrial cancer and is classified as simplex important to deliver in a hospital with blood or complex and with or without atypia.