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The risk of spreading the virus may also be increased by cardiopulmonary resuscitation erectile dysfunction treatment san antonio purchase kamagra polo overnight, bronchoscopy impotence grounds for divorce in tn kamagra polo 100mg for sale, endotracheal intubation erectile dysfunction tools buy kamagra polo from india, airway and sputum suction (Loeb erectile dysfunction new zealand kamagra polo 100 mg with amex, M erectile dysfunction treatment gurgaon buy on line kamagra polo. Nocosomial spread was reduced through use of surgical masks erectile dysfunction pills natural purchase genuine kamagra polo line, gloves and gowns (Seto, W. Thus patients are most infectious at the time of seeking health care (McDonald, L. A superspreading event was believed to be involved in the rapid propagation of the virus in the Amoy Gardens apartment building outbreak, where more than 300 residents were infected, presumably by a single patient (Cleri, D. Unfortunately, the initial symptoms and clinical appearance are not easily distinguishable from other common respiratory infections, and fever may be absent in older adults. The infection progresses through an inflammatory or exudative phase (characterized by hyaline-membrane formation, pneumocyte proliferation and edema), a proliferative phase and a fibrotic phase (Gralinski, L. In the first week after infection, symptoms usually consisted of fever and myalgia. Seroconversion was detected during the second week and was followed by a reduction of viral load. Nearly 100% of adults and children presented with fever, and approximately half with cough and/or myalgia. Others presented with symptoms unexpected in a respiratory infection, such as acute abdominal pain (Poutanen, S. During the outbreak, about 40% of infected patients developed respiratory failure requiring assisted ventilation, however 90% of patients recovered within a week after the first appearance of symptoms. Smokers required mechanical ventilation more frequently than nonsmokers (Poutanen, S. Older patients had greater morbidity and mortality, the result of an 10 aging-related attenuation in the adaptive immune response (Frieman, M. Independent correlates of adverse clinical outcome included known history of diabetes/hyperglycemia (Yang, J. Symptoms included chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep (Moldofsky, H. The virus is a cause for concern due to its zoonotic potential and the high case fatality rate (approximately 35%) (Li, F. The protease furin activates the S protein on the viral envelope, mediating membrane fusion and enabling virus entry into the host cell (Banik, G. Some patients present with gastrointestinal symptoms, including diarrhea, nausea and vomiting, and abdominal pain. Symptoms and manifestations of Middle East respiratory syndrome range from mild or asymptomatic infection to severe pneumonia, acute respiratory distress, septic shock and multiorgan failure resulting in death (Zumla, A. While the early case-fatality rate was close to 60%, this has decreased with improved awareness and surveillance; however, mortality remains above 35% (Al-Tawfiq, J. The probability of a fatal outcome is much greater among patients aged 50 years and older as compared to younger patients (77% vs. Mortality is also higher in men and in patients with multiple comorbidities (Banik, G. Several cases later occurred in clusters, including a hospital outbreak in Saudia Arabia, and confirmed that the virus can be transmitted between humans during close contact (Assiri, A. As of November 2019, the World Health Organization had been notified of 2,494 laboratory confirmed human cases of infection with the virus and 780 related deaths (case-fatality rate 37. However, a study of the general population of Saudi Arabia suggests that the rate of asymptomatic disease is much higher. The researchers estimated that approximately 3,300 cases of severe disease occurred in that span of time, a number that is 2. Nonethless, experts advise increased surveillance and active contact tracing as well as thorough investigation into potential animal hosts and routes of zoonotic reinfection, which appears to be perpetuating the outbreak (Breban, R. With an R0 of less than 1, chains of disease transmission are not self-sustaining in the presence of effective infection control measures (Zumla, A. Facts about 2019-nCoV In late 2019, a new coronavirus began causing febrile respiratory illness in China. Following an incubation ranging from 2-14 days, 2019-nCoV infection manifests as respiratory illness ranging from mild to severe, with symptoms that include fever, cough and dyspnea. In an early description of 41 clinical cases, patients had serious, sometimes fatal, pneumonia. Although the early case-fatality rate appeared to be low, the rapid spread and ease of transmission of the virus, even by asymptomatic individuals, is causing global alarm: experts point out that although a virus may pose a low health threat at the individual level, if easily transmissible it can nonetheless pose a significant risk at the population level. Diagnosis may be confirmed by chest radiography if there is evidence of infiltration consistent with pneumonia or respiratory distress syndrome. Neither virus isolation in cell cultures nor electron microscopy are sensitive enough for general diagnostic use and both methods are inconvenient. When appropriate, other epidemic or population-wide diseases may also need to be taken into consideration. Washing hands with soap and water or with alcohol-based handrubs is effective for interrupting virus transmission. Airborne precautions should be applied especially when performing aerosol-generating procedures such as intubation (Ben Embarek, P. The previous reporting requirements, formulated in 1951, required reporting for plague, cholera and yellow fever only, and the resulting delay in reporting cases early in the outbreak was likely to have contributed to its rapid spread (Enserink, M. Vaccines the successful containment of coronavirus epidemics in farm animals by vaccines, by either killed or attenuated virus, points to the potential success of vaccine programs. The S protein is currently considered to be one of the most promising targets for coronavirus vaccine development (Song, Z. The following table presents an up-to-date overview of the development of potential coronavirus vaccines. Supportive care is the mainstay of treatment for patients with severe disease (To, K. Some nonspecific immunosuppressive treatments or broad spectrum antiviral agents, such as ribavirin, were of limited success (Lee, N. Some physicians preferred to delay administration of corticosteroids until the second week of infection in order to reduce side effects. In the case of ribavirin, 26 trials were inconclusive and four suggested potential harm. Ribavirin and interferon were the most widely used combination in observational studies, and may warrant further investigation (Momattin, H. Broad-Spectrum Antiviral Agents Ribavirin is a ribonucleoside analogue that is active against some coronaviruses, as well as respiratory syncytial virus and metapneumoviruses. Unlike other infections agents (bacteria, fungi and parasites), viruses share extremely few common features that could be targeted by broad-spectrum agents. The development of broad-range agents requires a better understanding of pivotal virus-host interactions and the identification of targetable host cell proteins involved. Viral Enzyme Inhibitors the process of coronavirus replication is well understood. Several unique steps have been identified as potential targets for antiviral drugs. Targeted inhibitors of the serine proteases, which are required to activate the viral infectivity of some coronaviruses, may block the later stages of the viral life cycle (Kilianski, A. Following successful preclinical evaluation of lopinavir/ritonavir plus interferon-beta1b, in which significant reductions in mortality were obtained in a marmoset model, clinical evaluation of the combination was recommended (Chan, J. Since the combination of lopinavir and ritonavir was already available in the Wuhan, China hospital where early 2019-nCoV-infected patients were treated, a randomized controlled trial was quickly initiated to assess the efficacy and safety of the combination to treat this emerging coronavirus infection (Huang, C. Elements of the viral replication process have also been identified as potential therapeutic targets, including viral helicase, features of which are highly conserved among different coronaviruses (Adedeji, A. Despite a good understanding of viral targets and the identification of potential antiviral agents in vitro and in animal models, however, these findings have not translated into efficacy in humans (Zumla, A. Nine patients were given the combination therapy, while 13 patients were treated with corticosteroids alone. Most significantly, the incidence of mortality in the corticosteroid therapy group was 7. Furthermore, chest x-rays were normal within four days of initiating combination therapy, versus nine days in the corticosteroid monotherapy group (Loutfy, M. However, Saudi Arabian scientists reported that clinical trials evaluating this therapy would be challenging due to the limited availability of suitable donors, i. The antibody was tested in animal models, in which it protected against acute lung injury. Neutralization of Middle East respiratory syndrome coronavirus has also been achieved using monoclonal antibodies. Tables may also include drugs not covered in the preceding sections because their mechanism of action is unknown or not well characterized. The targetscape shows an overall cellular and molecular landscape or comprehensive network of connections among the current therapeutic targets for the treatment of the condition and their biological actions. Purple and pink text boxes indicate extracellular and intracellular effects, respectively. Enrollment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first 5 participants at the previous lower dose in each group. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment. At week 60, vaccine-induced humoral and cellular responses were detected in 51 of 66 participants (77%) and 42 of 66 participants (64%), respectively. The study will assess the safety of the vaccine and immune responses to the vaccinations. Themis has established a versatile technology platform for the discovery, development and production of vaccines as well as other immune system activation approaches. The 16 month study will enroll approximately 48 evaluable subjects, with 8 subjects in each one of six sequential ascending intravenous dose cohorts. The highest tolerated dose in the study, 50 mg/kg, was recommended for initial use in human efficacy trials (Beigel, J. The primary and secondary goals of the trial are to obtain safety and immunogenicity data. Inovio and 29 GeneOne are also working on a preclinical vaccine for the emerging Zika virus (see Thomson Reuters Drug News, January 26, 2016). Anemia, Iron Deficiency Iron deficiency anemia is one of the most common nutritional disorders and is due to excessive loss, deficient intake or poor absorption of iron. Red cells appear abnormal and are small (microcytic) and pale (hypochromic) in iron deficiency anemia. It is released from the liver and cleaved in the circulation by renin to form the biologically inactive decapeptide angiotensin I. See also Renin-Angiotensin System Anorexia A condition charaterized by an abnormal loss of appetite or an aversion to food. Anorexia Nervosa See Anorexia Antibody A protein synthesized by B lymphocytes in response to an antigen that has the ability to specifically bind with said antigen. Igs are produced in many different forms, each with different amino acid sequences and antigen binding sites. Through recruiting the complement system and various white blood cells, they protect the body by inactivating viruses and bacterial toxins and by killing invading microorganisms and larger parasites. Antigenic Drift Minor changes in viral proteins (antigens) due to gene mutations within an influenza hemagglutinin or neuraminidase subtype. Antigenic Shift the sudden emergence of a new strain of influenza due to an abrupt change in the influenza hemagglutinin or neuraminidase protein type on the viral surface. These nucleotide sequences are not templates for synthesis but interact with complementary sequences in other molecules thereby affecting their function. Antisense oligonucleotides have been used to inhibit viral infections and to treat cancer and other diseases. Autosomal Recessive A genetic trait that is only expressed when it is present on both alleles of a gene. The risk of transmitting an autosomal recessive disease is 1/4 (25%) at each pregnancy. Bioavailability the proportion of an administered drug absorbed into the bloodstream, indicating the physiological concentration of that drug. Biomarker Characteristic that is objectively measured and evaluated as an indicator of normal biological processess, pathogenic processess or pharmacologic responses to a therapeutic intervention. Acute bronchitis occurs suddenly and is resolved within a few days, while chronic bronchitis persists over a long period of time and may recur over several years. Bronchus One of two subdivisions of the trachea that conveys air to and from the lungs. Bronchi are lined with stratified ciliated columnar epithelium, possess a lamina propria and are composed of longitudinal networks of elastic fibers. There are three types of A subunits and two types of B subunits encoded by different genes. This cell does not mature noramlly and eventually die but it divides prolifically. Cancers arising from epithelial cells are called carcinomas and those arising from mesenchymal tissues are called sarcomas. These molecules display a certain degree of selectivity for various immune cell types and are involved in activation of leukocytes during transendothelial migration and chemotaxis in tissues. It is created by fusing two early blastula stage embryos, by reconstituting bone marrow in an irradiated recipient or by somatic segregation. Chlamydia A genus of prokaryotes that replicate in cytoplasmic vacuoles within susceptible eukaryotic cells. Chlamydia pneumoniae A bacteria belonging to the Chlamydiaceae family that causes pneumonia and diseases of the upper and lower respiratory tract. Consolidation the solidification into a firm dense mass as in inflammatory induration of a normally aerated lung due to the presence of cellular exudate in the pulmonary alveoli. Corticosteroids A class of steroid hormones that are produced in the adrenal cortex and are involved in many physiologic processes including among others stress responses, immune responses, inflammation, carbohydrate metabolism, protein catabolism, electrolyte homeostasis and behavior.

Women have two X chromosomes and men (A) and guanine (G) which are purines erectile dysfunction doctor milwaukee discount kamagra polo 100 mg overnight delivery, and thymine (T) have one X and one Y chromosome zocor impotence purchase kamagra polo 100mg otc. The gene that result in a change which is biologically signif amino acids are then joined together to form a polypeptide cant erectile dysfunction pills that work generic 100mg kamagra polo overnight delivery. The actual process of polypeptide synthesis as a result of a mutation in that gene would lead to an takes place on cytoplasmic organelles called ribosomes erectile dysfunction protocol scam or real kamagra polo 100 mg mastercard. The coding region (red) mutation (frameshift is the information used to define the sequence mutation) of amino acids in the protein impotence in women generic 100 mg kamagra polo with amex. The law of segregation oligogenic erectile dysfunction vacuum discount 100mg kamagra polo free shipping, polygenic refers to the behaviour of the chromosomes in meiosis. Pedigree of a family dent assortment means that inheritance of eye colour is in with Marfan syndrome. Pedigree chart of a family transmission with fxed predictable risk ratios and the risk with severe retinitis pigmentosa. Key to symbols used in pedigree charts Consultand: individual(s) seeking genetic counselling or testing Proband, propositus, index, case, or person examined who is the beginning of analysis or first affected family member coming to medical attention Deceased Pedigree symbols and abbreviations for pregnancies not carried to term. Offspring are depicted from left to right in descending order of age and denoted by Arabic numerals. This has to be ac Both males and females are equally at risk but sex infuence counted for when plotting the family tree for members who is sometimes seen such as in Fuchs endothelial dystrophy are younger than the age of manifestation of the disease. Risk to the off-spring is 25% if both parents are Certain forms of autosomal dominant mutations, such carriers, 50% if one is affected and the other a carrier as those causing Marfan syndrome and achondroplasia, and 100% if both are affected. X-linked Recessive Trait Many ocular diseases are inherited as X-linked recessive Autosomal Recessive Traits traits. There is a 50% risk for of chromosome 13 (13q associated with retinoblastoma), the daughters of a female carrier to become carriers and a deletion of a part or the entire short arm of chromosome 50% risk for her sons to be affected. Female-to-female transmission of Cytoplasmic or Mitochondrial Inheritance disease is seen, unlike in X-linked recessive and there is a theoretical risk for female members in the family to be Also known as maternal inheritance, cytoplasmic or mito affected at a rate twice as high as males. This is termed as polygenic ova but are lost by spermatozoa, and the few remaining to or multifactorial inheritance. Structural defects in chromo gene gives us a better understanding of human genetics in somes are detected by karyotype analysis and band-staining general. This enables us to protect future generations, to techniques using peripheral lymphocytes obtained by vene some extent, by genetic counselling, and opens the door to puncture. Earlier, bone marrow cells and fbroblasts obtained the possibility of cure by gene therapy. Chromo Several inherited eye diseases are due to defective somal abnormalities of the sex chromosomes are less severe. Better knowledge and Since this modifed recombinant engineered virus is now understanding of how mutated genes cause human ocular devoid of the normal viral genes required for its own disease will lead to improved methods of diagnosis and treat replication, the virus cannot proliferate and does not kill ment and eventually will improve the prognosis for vision. The There are also diseases caused by mutations that pro symptoms can be treated by medication, replacement ther duce gene products which are destructive to the cell. In some diseases a true cure at the molecu a useful approach for those diseases that are caused by lar level can be attempted. In summary, most approaches to gene therapy are At present, recognition of the limitation of therapy in presently targeted to the restoration of function in the genetic disorders and the reliable predictability of the pat somatic cells of the particular tissue affected (somatic tern of transmission of genes from one generation to the cell therapy). Evaluation of alternative (non-viral) means next has led to the realization that prevention is the most of introducing therapeutic genes is under way. This approach includes genetic screening, genetic matic cells affected by the disorder. In order to prevent either in the form of (i) complete absence of the protein or transfer of the disease to the progeny or offspring of the (ii) formation of a defective protein, which may not func affected individual, the gene therapy must be targeted at tion normally or attain a new function that may be harmful the germ-line cells. The new useful gene is selected lymphoma), relapsing or refractory neuroblastoma, and such that it either codes for a normal protein, or codes for even retinoblastoma. Chapter | 33 Genetics in Ophthalmology 559 effcacy of treatment or study the dynamics of stem cell disease and provides an option for the couple to have behaviour in vivo. A family pedigree up to a minimum of In summary, gene therapy has the potential to revolu three generations must be charted (Figs 33. The tionize the way in which diseases are treated but the feld information must then be assembled to determine the pat needs time to mature scientifcally with due attention to the tern of transmission within the family and compare it with future medical, economic and ethical ramifcations of this the pattern expected for that particular disease condition. Depending on the type of inheritance of disease (mono genic, multifactorial or chromosomal) and the reliability Genetic Screening of the diagnosis, the risk to subsequent offspring may be predicted with a fair degree of accuracy. In addition to Genetic screening programmes are for autosomal reces determining the risk, other information to be obtained prior sive disorders and are of two types: (i) homozygote to counselling includes the prognosis and treatment of screening or the search for individuals who have the the disorder and the availability of prenatal diagnosis and disorder and (ii) heterozygote screening or the search for testing for the carrier state. Successful homozygote certain congenital malformations and psychiatric disorders screening programmes have been put into practice in is presently imperfect and will remain so until we have a screening newborns for diseases such as phenylketon better insight into the complex interaction of the various uria, homocystinuria, maple syrup urine disease, galac genes and environmental factors which lead to the manifes tosaemia, cystic fibrosis, hypothyroidism and sickle cell tation of the disease. Ashkenazi produce only affected progeny, though there are rare excep Jews, in whom carrier frequency is as high as 1 in 25 as tions to this rule such as if there are different mutations in compared to approximately 1 in 300 in Anglo-Saxons) is the same gene which compensate for each other. In the case of a person who is Prenatal Diagnosis affected by an autosomal recessive disease (homozygous Following genetic counselling, the couple at risk for hav for the defective gene), 50% of the offspring will be ing a child with a genetic disorder has certain options, carriers. With cessive trait and partners a normal person, then 50% of their low risk or mild disease they may be reassured and may offspring will be carriers. On the other hand, in the case of fected female carrier to her daughters who will also be high-risk diseases with high morbidity they may perceive carriers with a risk of 50% for transmitting the disease. These disorders can also be passed from an In case both parents are heterozygous for an autosomal affected father to all his daughters, who will be carriers and recessive disease, they may choose to utilize artifcial at risk to a tune of 100% of becoming carriers, but are never insemination by an unaffected donor to reduce the risk. Finally, if the disease can be detected antena male to 100% of his daughters and none of his sons. The frequency and severity chromosomal and multifactorial disorders and up to 50% of the disease in the offspring depend on the number of for autosomal dominant disease. Very few mitochondria in comparison of the risk of the diagnostic procedure with the developing embryo are derived from the sperm; the risk of having an affected child. The choice of a par so males affected by mitochondrial disease rarely have ticular method of diagnosis is determined by the disease affected children. Chapter 34 the Causes and Prevention of Blindness Chapter Outline What is Blindnessfi The consequences placed in category 4, even if visual acuity is not impaired affect not only the individual but also the family and the (Table 34. Another 135 million people are deemed to be or early childhood has unique problems. In India, under the National Programme for Control of Blindness, l How do we define blindnessfi The geographic distribution of blindness shows that the l Why are people blind or what is the aetiology of blindnessfi National priorities Aetiology 1998 (40 Million) 1995 (38 Million) are set and programmes instituted to combat blindness. Cataract 43% 50% General and specifc details will be elaborated throughout Glaucoma 15% 15% the chapter. The Trachoma 11% 15% (trachoma/ corneal scar) approach to planning and implementation of blindness con trol measures should be based on (i) strategy, (ii) disease, Vitamin A 6% 4% (childhood (iii) services and (iv) community. Strategies for the control of blindness include: Others (diabetic 24% 8% (diabetic l Primary prevention, or the prevention of the dis retinopathy, macular retinopathy) ease occurring in the first place degeneration, optic 1% (trauma) l Secondary prevention, or the prevention of visual neuropathy, etc. A disease-oriented approach to blindness involves: national programmes, 2nd edition. The occur in specifc localized areas of the world, affect commu various levels include: nities, start in childhood, can be controlled with medicines l Primary care services at the community level and do not necessarily need an eye specialist for treatment l Secondary care services at the eye clinic level. This includes services provided by general medical the geographical distribution of the major causes of doctors and non-ophthalmologists, and blindness in the world today is another aspect worth paying l Tertiary care services at the training or referral cen attention to . The proportion is not uniform throughout the tre level and includes all eye specialists world (Table 34. A community approach for specific blindness control measures is directed at the target population at risk. This strategy is useful for Vitamin A defciency Diabetic retinopathy cataract, glaucoma and blinding trachoma with trichiasis. To be effective it has to be supported and who has decreased vision which is recorded to be worse sustained by an effective and adequate referral system and than 6/18 in any eye. The clinical activities of the establishment of an effective eye care delivery system the primary care worker are classifed as (i) those pertaining for the treatment of eye diseases and prevention of blind to diseases which should be recognized and treated by a ness is linked to the existing general health services and trained primary health care worker such as acute conjuncti resources available (Flowchart 34. Actions include administration areas, with the assistance of several non-governmental of antibiotics and referral to the next level if needed. A capsules, zinc sulphate eye drops, bandages, sticking l the teams provide comprehensive eye care facilities plaster, epilation forceps and eye shields. Pro grammes set the goals according to local problems and Tertiary Eye Care priorities and then, based on the fnancial and human re sources available, set targets for achieving the goals. It is Tertiary care units are large institutes in urban centres usu recommended that blindness prevention be based on activi ally linked to major hospitals and medical colleges, which ties related to primary health care (for example, vitamin A have all the state-of-the-art diagnostic and therapeutic defciency) but also be supplemented by provision of de facilities. These provide the following services: fnitive management at the secondary level for the treatment l Management of less common blinding conditions which of common blinding conditions such as corneal ulcers, require highly specialized staff and expensive, sophisti ocular trauma, acute angle-closure glaucoma and cataract cated equipment surgery. The treatments available for the pre implementation and retention of the system, ensure equi vention and cure of blindness are among the most suc table distribution in the country, even in geographically cessful and cost effective of all health interventions. It is remote areas and under-privileged sections of society estimated that unless prompt, effective and preventive who may be physically present in non-remote areas such health promotional measures are undertaken and imple as urban slums. It is also well recognized that the of all activities, maintenance of records and evaluation burden of blindness has an enormous personal, social and analysis of the impact of the programme are also and economic impact, limiting the educational potential important. At the 56th World Health Assembly in May 2003 Center of 20 a Vision 2020 resolution was accepted urging all member Excellence states to develop, implement and evaluate national plans and Training district/region/province plans to enable the Vision 2020 con 200 Centers cept to be introduced at the community level, especially in rural areas where the need for blindness prevention is most Service Centers 2000 required and where the greatest progress can be achieved. All these factors contribute to the development of cataract at Interventions for Prevention and Treatment an earlier age. In addition, cataract progresses faster in Vision lost due to glaucoma cannot be regained. In a screening programme the intraocu guideline (usually,3/60 or,6/60) for surgery. He or she lar pressure measured by a standard instrument (generally plays a role in counselling and motivating those affected to Goldmann applanation tonometer) is useful. Two-stage screening techniques have often been genital cataract, subluxated lens, complicated cataracts employed where intraocular pressure readings are taken and cataract associated with systemic diseases such as in large populations, and those with elevated pressures or uncontrolled or inadequately controlled diabetes. In addi fundus changes are further subjected to visual feld exami tion, tertiary care centres have the responsibility of train nation. Diabetic Retinopathy Primary angle-closure glaucoma is comparatively rare in Caucasian populations as it accounts for about 10% of glau Global View comas in these communities, but it is more common among Though originally perceived as being predominantly a dis Asians, accounting for 50% of glaucoma in countries such ease of developed countries, diabetic retinopathy has shown as India. Basically the choice of method selected for Aetiology screening and referral are determined by the availability Two different classifcation systems are used to categorize of personnel and fnancial resources in the particular the different causes of impaired vision in children. If either is present, referral to in Children* a specialist for laser photocoagulation is required. Whole globe: microphthalmos, anophthalmos, phthisis bulbi, atrophic bulbi Principles include identifcation of the population at risk and implementing pre-emptive measures. Other: cortical blindness, amblyopia Aetiological classifcation Action to be Taken at the Secondary Level Hereditary: chromosomal disorders, single-gene defects this includes proper management of eye injuries, corneal Intrauterine: congenital rubella, foetal alcohol syndrome ulcers, correction of refractive errors and appropriate refer ral of cases to a tertiary-level eye facility if required. Perinatal: ophthalmia neonatorum, retinopathy of prematurity, birth trauma Action to be Taken at the Tertiary Level Childhood: vitamin A defciency, measles, trauma At this level, screening and treatment of retinopathy of Unclassifed: impossible to determine the underlying cause prematurity is carried out, as well as management of cata ract, corneal scars, glaucoma, strabismus and complicated *Childhood blindness. Severe keratomalacia is usually seen below 5 years Ophthalmia neonatorum of age and is particularly common in children between 6 months and 3 years of age. Since affected individuals Obvious developmental abnormalities such as microphthalmos and anophthalmos are young, the impact in number of blind person-years is tremendous. The treat School ment schedule for individuals with keratomalacia is outlined Refractive error in Chapter 15. As vita and East Asia, Africa, parts of South and Central America, min A is teratogenic in high doses in early pregnancy, it the Eastern Mediterranean and Western Pacifc regions. Thus, the timing of supple Aetiopathogenesis mentation is critical and should be at birth or within Nutritional blindness (keratomalacia) results from pro 1 month of giving birth. Vitamin A is required for specifed for keratomalacia, but a single dose per episode vision, maintenance of the integrity of epithelial linings, is recommended as opposed to keratomalacia, in which growth and immunity. The vitamin A status of min A-rich foods are carrot, mango, papaya, dark green leafy an individual depends on the intake of retinal (vitamin A) vegetables and are all relatively inexpensive. Neonates get egg, fsh, milk and whole milk dairy products, but are more their vitamin A stores from the mother in utero and then expensive and are generally not available to families in high acquire it from the breast milk after birth. In many rural communities in developing countries, par It is well known that blinding trachoma is linked with pov ticularly in areas with hot, arid climates, endemic trachoma erty, overcrowding, inadequate face-washing, non-availability is still a major cause of blindness. Aetiopathogenesis Trachoma is a chronic infammatory disease of the surface Community Diagnosis of the eye affecting primarily the conjunctiva, but later Blinding trachoma is recognized to be prevalent in a com secondarily affecting the lids and the cornea. The organism munity if the prevalence of severe visual loss due to corneal responsible is Chlamydia trachomatis. Surgical correction of entropion and trichiasis has Trachoma is spread by eye-to-eye transmission through an immediate effect in preventing blindness, provided the fomites and housefies. In some communities with blinding Antibiotic treatment aims (i) to reduce the severity trachoma there are regular epidemics of non-chlamydial of infammation in active trachoma, thereby reducing the conjunctivitis once or twice a year, or a continuous preva potential for scarring and severe blinding complications, lence of bacterial and/or viral conjunctivitis all the year and (ii) to decrease disease transmission. The (topical and oral), erythromycin (oral), sulphonamides combination of active trachoma and recurrent episodes (oral) and rifampicin (oral) are effective drugs.

In doubtful cases erectile dysfunction pills images buy kamagra polo 100 mg lowest price, an X-ray of the paranasal sinuses Lymphangioma Haemangiopericytoma would help confrm the diagnosis erectile dysfunction treatment pumps generic 100mg kamagra polo amex. Plexiform meningioma neurofbroma Schwannoma Neurofbroma Wegener Granulomatosis Mesenchymal Rhabdomyosarcoma Fibrous histiocytoma this is a rare insulin pump erectile dysfunction kamagra polo 100 mg sale, chronic disease affecting the upper respira tory tract bisoprolol causes erectile dysfunction discount kamagra polo 100 mg amex, lungs and kidneys and characterized by wide Haemopoietic Acute myeloid Lymphomas spread distribution of necrotizing angiitis with surrounding leukaemia granuloma formation erectile dysfunction drugs names order kamagra polo 100mg fast delivery. Histiocytosis the most common sign of Wegener granulomatosis is involvement of the upper respiratory tract chlamydia causes erectile dysfunction generic 100mg kamagra polo with amex, which occurs in Metastatic Neuroblastoma Breast, lung, prostate Wilm tumour carcinoma nearly all patients. Symptoms include pain in the paranasal sinuses, discoloured or bloody nasal discharge and, occa Ewing sarcoma sionally, nasal ulcerations. Ocular manifestations occur secondary to an adjacent granulomatous sinusitis or as a result of focal vasculitis. The nasolacrimal duct may be obstructed and there may be episcleritis, scleritis, proptosis and extraocular muscle or optic nerve involvement. Standard therapy consists of a combination of a cortico steroid that reduces infammation and a cytotoxic drug that interferes with the abnormal growth of cells. Cyclophosphamide is the preferred cytotoxic drug when used in low dosage with careful monitoring of the white blood cell count. Clinically they may be mistaken for meningoencepha loceles (protrusions of the cerebral contents), which usually occur at the upper and inner angle where there are the most Benign Growths sutures between the bones. In the latter (i) the tumour is these include dermoid cyst, dermolipoma angioma, osteoma immovably attached to the bones; (ii) the hole in the bone (Fig. These lesions vary in size, have smooth Orbital Haemangiomas contours and are non-invasive. The lesions are well these are commonly capillary in the younger age group defned with internal spaces giving rise to a characteristic and cavernous haemangiomata in the elderly (Fig. If vision is threatened in young children, treatment may be with oral, intravenous or Orbital Varices Orbital varices are due to an engorgement of the orbital veins. Surgical excision is required for laser tumours producing a cosmetic blemish or functional dehiscence. Haemopoietic Tumours these may occur as various types of reticular tumours (lymphoma, lymphosarcoma, reticulosarcoma, Hodgkin disease, etc. Proptosis may occur due to deposits in the orbit itself or the lacrimal gland (Fig. In adults, dissemination occurs in half the cases and radiotherapy alone is probably the best initial treatment. Cytotoxic therapy should be held in reserve for those cases which later show evidence of dissemination. Simple glial tumours derived from astrocytes and oligo dendroglial cells of the optic nerve are either a solitary manifestation or a component of von Recklinghausen neu rofbromatosis. There may be a place for radical surgery for a minority of patients in whom there is progressive growth without evidence of chiasmal involvement. Patients present with swollen or Malignant tumours of the orbit are usually sarcomata, atrophic optic discs when frst examined and, in many although carcinomata derived from the lacrimal gland or by cases, opticociliary shunt vessels are present, particularly extension from the nasal mucous membrane also occur. Patients with relatively good vision are is by biopsy in which cross-striations in the tumour cells are kept under observation until it deteriorates and then the pathognomonic. The treatment of rhabdomyosarcoma is a combination Biopsy or any surgery which transgresses the dura is to be of chemotherapy and radiotherapy. Two injections of vin avoided unless the rate of growth suggests a malignant cristine, cyclophosphamide and actinomycin D are given type of meningioma, when biopsy is indicated. After radiotherapy, a combination of vincristine, Apart from those originating in association with the cyclophosphamide and doxorubicin is given three times optic nerve sheath, meningiomas generally arise in associa weekly for a year or longer in those patients in whom tion with the intracranial meninges and invade the orbit metastases were detected. In adults metastasis commonly originates from the lung, thyroid, breast and prostate, and nasopharyn Therapy of Orbital Tumours geal carcinomas spread into the orbit most frequently. In young children neuroblastomas from the adrenal medulla A thorough evaluation of the orbit by ultrasound (Fig. Anterior masses can be subjected to a fne needle biopsy or, if necessary, an explor Malignant Nasopharyngeal Tumours atory operation with removal of a portion of the growth for these form 0. It ophthalmoneurological symptoms, these being the earliest may be feasible to remove dermoid cysts and some other signs in 16% of cases (Fig. The ffth and sixth benign tumours without injury to the globe, although its nerves are most frequently involved; more rarely the third, mobility is likely to be impaired in extensive operations. These changes are bital extension of malignant intraocular growths (retino probably due to a generalized disturbance of the endocrine blastoma, malignant melanoma of the uveal tract), it system, possibly associated with the thyrotrophic hormone may be necessary to remove all the contents of the orbit by secreted by the anterior lobe of the pituitary gland which exenteration. From the the level of the lateral canthus over the zygomatic arch for ocular point of view, the exophthalmos in the early stages about 4 cm. The bone is cut through at the upper and lower may be unilateral but usually becomes bilateral. A peculiar outer angles of the orbit with a Stryker saw and bone, stare with retraction of the upper eyelid is seen, so that muscle and skin are refected backwards in one fap. The there is an unnatural degree of separation between the part of the orbit immediately posterior to the globe is thus margins of the two lids (Dalrymple sign, Fig. Exenteration would delay this symptom is not always present and may occur or prevent systemic spread of the disease. The lids may be re frequency of blinking with defcient closure of the lids tained if they are not implicated in the growth, but the free (Stellwag sign). If vergence (Mobius sign), and often the skin of the eyelids this is not done the lashes are troublesome when the lids shows pigmentation. Ophthalmoscopically, veins and become retracted into the orbit, as invariably follows. One or more of the cardinal symptoms may be at the margin of the orbit in its whole circumference. The common signs of Graves disease are listed in orbital contents are separated from the walls by a periosteal Table 30. A mild exophthalmos may be associated with thyrotoxicosis and an extreme exophthalmos in any state of thyroid activity, but usually in hypothyroidism, often after a thyroidectomy. The retraction of the lid in thyrotoxicosis is due to con traction of Muller muscle owing to the sensitizing action of thyroxine on sympathomimetic receptors. Once the disease stabilizes, myopathy, lid retraction and minor corneal exposure require an elective lateral canthoplasty with release of the upper and lower retractors of the Exophthalmic ophthalmoplegia usually commences in eyelid. The ocular muscles are enor Pulsatile Proptosis mously swollen, pale, oedematous and infltrated, giving rise to an irreducible exophthalmos which may easily result this is generally due to an arteriovenous fstula, the com in the development of an exposure keratitis or even disloca munication taking place between the internal carotid tion of the globe. The disease runs a self-limited of the conjunctiva and lids are widely dilated (Fig. Retained foreign bodies are liable to set up is often considerable pain from stretching of the branches suppuration and orbital cellulitis. These resolve into densely scarred areas fringed most cases subsides spontaneously. Both eyes applied to the carotid artery stops the pulsation, ligation of should be examined as the missile may have traversed the carotid artery may affect a cure, but recurrence of both orbits. Ligation of Non-penetrating Injury both internal and external carotids does not appear to give better results. Forward this procedure also may fail to relieve the condition, dislocation of the globe between the lids occurs most and in these cases intracranial ligation proximal and distal often when the blow is directed from the outer side where to the aneurysm has been practised, but is both diffcult and the orbital margin affords least protection, but does not dangerous. Injuries to the bone most commonly affect the margin of the orbit but deep fractures may be caused by pene Intermittent Proptosis trating wounds or by severe contusions. It is sema, which may cause proptosis, but is usually most usually due to varicosity of the orbital veins and has also evident in the lids. The signs depend upon the object transmits force into the orbit, which is then refected particular structures injured. As the orbital foor fractures, the eye and its sur injury or damage to the motor nerves. The optic nerve rounding tissues may collapse into the maxillary sinus, may be injured or severed with resultant atrophy. Avul causing enophthalmos and entrapment of the inferior sion of the optic nerve head, with the formation of a rectus muscle. Such fractures are diag the treatment of a retained foreign body depends upon nosed accurately by computerized coronal tomography its situation and the probability of subsequent infection. If the position is such that serious Tomography can be used to estimate the size of the manipulations would be necessary for its removal, and if fracture. Large fractures (greater than one-half of the orbital there is evidence that the substance is aseptic, expectant foor) need early repair, preferably within 2 weeks after treatment may be adopted. If suppuration occurs, the injury, as do fractures producing substantial muscle foreign body must be removed and the case treated as dysfunction due to entrapment of the tissue. The orbital vascular channels A study and teaching collection of clinical ophthalmic cases and their are connected with the intracranial system and infectious pathology. Ultrasonography and other radiological investigations help in the diagnosis and management of orbital lesions. Invasive investigations like fine needle aspiration cytology and orbital biopsy are required in specific situations. Ocular examination should specif they are readily explained by the anatomy of that part of the cally include visual acuity, visual felds, colour perception, nervous system. More importantly, there are several poten extraocular movements including nystagmus, and fundus tially serious diseases of the nervous system which may copy for papilloedema or optic atrophy. The craniopharyngioma, lesions at the orbital apex especially commonest clinical form is homonymous hemianopia, in bone fragments in fractures of the optic canal, haemorrhage which the right or left half of the binocular feld of vision is of the optic nerve sheath and dysthyroid ophthalmopathy. This condition is due to a lesion where attempts are made to demonstrate the physiological situated in any part of the visual paths from the chiasma to and metabolic functions of parts of the brain and their the occipital lobe. A non-invasive, well tolerated, relatively inex often discovered when the patient does not see food on the pensive technique which is effective in rapidly studying left side of the plate. Optokinetic testing in occipital lobe hemianopias should elicit a normal response to each side. Partial giomas, temporal lobe gliomas or aneurysms of the upper hemianopia of a quadrantic type is then commoner than basilar distribution or on the superior cerebellar arteries or the typical homonymous defect, usually greater on the posterior cerebral arteries are the common causes. Lesions of the Optic Chiasma Bitemporal hemianopia is usually caused by tumours in Lesions of the Optic Tract the region of the sella turcica, pressure by a suprasellar In these cases, since the afferent pupillary fbres part com aneurysm or by chronic arachnoiditis; these press upon pany with the visual fbres before the latter enter the lateral the chiasma, so that the fbres going to the nasal halves geniculate body, Wernicke hemianopic pupil reaction of each retina are destroyed (Fig. Tumours of should be present, but the reaction is always diffcult to the pituitary body are most common; but suprasellar elicit. More assistance in diagnosis is afforded by collateral tumours, particularly craniopharyngiomata derived from symptoms. The earliest visual symptoms of the pituitary fossa or vascular calcifcation; simple may be a unilateral central scotoma simulating retrobulbar radiography should be supplemented by computerized neuritis, for one side is usually compressed before the other. If, as frequently occurs, vision progressively There may be contralateral superior quadrantanopia due deteriorates, transfrontal or nasopharyngeal extirpation to involvement of von Willebrand knee which consists of may be advisable in many cases, particularly of pituitary fbres from the inferonasal retina of the other side which tumours; the prognosis of operative removal, if undertaken loop forward slightly into the opposite optic nerve after in time, is reasonably good. Neurological disorders can affect the control of eye move More commonly, bitemporal hemiachromatopsia, passing ments by involving the higher cortical centres (supranuclear into a bitemporal hemianopia, supervenes. Lesions of the nerve type and progress of the visual defects are thus not uncom trunks could be anywhere along the intracranial course or mon. This often occurs because of variation in the site locally in the orbit and could be due to compression, isch of pressure and also anatomical variations in the position aemia or infammation. It may be due to distension of the only through the absence of mid-brain or peripheral nerve third ventricle, causing the optic nerves to be pressed down disease. It is found with cerebellar tumours, acoustic sensory-motor apparatus controlling normal binocular neuromas, compressive lesions, platybasia and vascular position. It is infrequent with Congenital jerky nystagmus is not associated with any demyelinating lesions. Pendular Chapter | 31 Diseases of the Nervous System with Ocular Manifestations 511 in extreme lateral position of the eyes. Nystagmus may be congenital or early infantile, or Types and Clinical Features it may be acquired. These two groups of cases should In congenital and early infantile nystagmus the patient be carefully distinguished on account of their different is wholly unaware of the movements, since objects do not pathological foundations. The cause in these cases is inability to develop cases of acquired nystagmus in adults, objects appear normal fxation. In such cases it may be necessary to examine the eye carried out by the rods alone, and there is therefore a cen very carefully with an ophthalmoscope because the pres tral scotoma. The nystagmus may disappear in alternating sursumduction or dissociated vertical devia one eye before the other; such cases may be mistaken for tion characterized by either eye slowly elevating with an true unilateral nystagmus. When either eye is covered, the There are some important types of nystagmus with lo nystagmus increases. It may be congenital or acquired and it may be features of the Sylvian aqueduct syndrome consist of: caused by blindness, or by lesions at the cervicomedullary junction. Adduction movements with attempted vertical gaze sions produce fast phase in the same direction.

In a Chinese study erectile dysfunction causes emotional order kamagra polo 100mg with visa, unilateral oophorectomy (with or without hysterectomy) performed before age of natural menopause was also associated with worse word recall erectile dysfunction shake recipe order generic kamagra polo canada, one of the first markers of dementia (Zhou erectile dysfunction treatment new zealand buy generic kamagra polo 100 mg, et al impotence new relationship order kamagra polo overnight delivery. Each year of earlier surgical menopause 100 was similar to the cognitive effects associated with 6 months of aging erectile dysfunction pump ratings purchase kamagra polo with a mastercard. An earlier age at time of surgical menopause also significantly decreased episodic memory (p = 0 erectile dysfunction pump prescription purchase kamagra polo with a visa. In this study, there was no association between age at natural menopause and cognition at follow-up. Several smaller prospective studies also showed that surgical menopause has an acute detrimental effect on cognitive (in particular verbal memory) function, although these studies were not limited to women who had undergone surgical menopause before the age of 40 (Sherwin, 1988; Nappi, et al. The negative effect on verbal memory was worse when surgery occurred at a younger age (Nappi, et al. Another prospective 6 month follow-up study of women (average age 41 years, n=53), undergoing surgical menopause indicated a decline in global cognitive function, whereas controls had stable function over time (Farrag, et al. No consistent conclusions could be drawn from the included studies as only few considered menopausal status as a possible contributor to cognitive dysfunction after chemotherapy and setup, data, and results are mixed. Differences in findings and the lack of strong conclusions may be explained by experimental design of the studies; not stratifying for age at induction, not including women with cognitive impairment or too young an age at assessment, not recording whether hormone treatment was given up to age 50, and whether or not hysterectomy had also been performed. Recommendation the possible detrimental effect on cognition should be discussed when planning hysterectomy and/or oophorectomy under the age of 50 years, D especially for prophylactic reasons. For older women (> age 60 years) the health risks of treatment exceed the benefits. The effect of different treatments on neurological function in Turner Syndrome girls has been reported in several studies from the same research group. The oxandrolone-treated group had improved performance on the working memory domain score after 2 years compared to the placebo group (p < 0. This study showed a decline in verbal memory performance which was reversed by estrogen treatment (as assessed by Paragraph recall, but not seen on Digit span or visual memory tests) (Sherwin and Tulandi, 1996). They also did not find an estradiol related improvement in cognitive test performance (no changes in measures of attention, concentration, or memory function (either verbal or visual)) (Schmidt, et al. These findings were consistent with a small study showing an average of 10 words more recalled after a high dose intramuscular injection of estradiol or testosterone (Sherwin, 1988). In the observational studies mentioned above investigating risk for cognitive impairment/dementia, estrogen treatment up to age 50 (Rocca, et al. However, duration of hormone use in this study was associated with slower decline in global cognition when administered within the 5-year perimenopausal window. This beneficial effect of hormone replacement in women who had undergone surgical menopause was not always found in one systematic review including women undergoing surgery pre and postmenopausal (without separate analysis) (Vearncombe and Pachana, 2009). The lack of effect in this group was also described by Rocca and colleagues (Rocca, et al. Finally, two observational studies reported that women with surgical menopause who were still using hormone therapy a decade after natural menopause (around age 60) actually had worse memory function than those untreated with hormones ((File, et al. Hence, the majority of these studies suggest that hormone treatment up to the age of 50 may be beneficial for neurological function in women who have undergone an early (surgical) menopause with hysterectomy and that this does not increase risk for dementia. Hormone treatment at an older age (>60 years of age) may confer added risk for dementia and vascular disease. Hormone treatment for dementia Two Cochrane reviews have suggested that neither transdermal estradiol nor conjugated equine estrogens have any positive effects on cognition in women without dementia (Lethaby, et al. However, some short-term positive effects on cognition (for up to 4 months) with either type of estrogen were 103 reported in women with dementia (Hogervorst, et al. Conclusions and considerations There is a relatively weak quality of evidence with contrasting conclusions ranging from no effect of estrogen treatment (Vearncombe and Pachana, 2009) to possibly some effect (Hogervorst and Bandelow, 2010; Hogervorst, 2013) to a substantial effect and risk for cognitive impairment/dementia without hormone treatment (Rocca, et al. Differences in meta-analysis conclusions may be due to insufficient analyses of differences in methods (Vearncombe and Pachana, 2009) or selective reporting (Rocca, et al. There is no evidence of adverse effects of estrogen replacement therapy on brain function before the age of natural menopause (at age 50) but this may not be true after the age of natural menopause. Hormone treatment should probably be part of a lifestyle change to reduce risk for vascular disorders associated with later life age-related cognitive impairment and dementia, such as lowering abdominal fat, hypertension, hyperlipidaemia, and insulin resistance risk in midlife by cessation of smoking, exercising and eating a healthy diet (Clifford, 2009). Baldereschi M, Di Carlo A, Lepore V, Bracco L, Maggi S, Grigoletto F, Scarlato G, Amaducci L. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Early age at menopause is associated with increased risk of dementia and mortality in women with Down syndrome. Gonadotropin hormone releasing hormone agonists alter prefrontal function during verbal encoding in young women. Trough oestradiol levels associated with cognitive impairment in post-menopausal women after 10 years of oestradiol implants. Sex steroids to maintain cognitive function in women after the menopause: a meta-analyses of treatment trials. Hormone replacement therapy to maintain cognitive function in women with dementia. Cognitive function across the life course and the menopausal transition in a British birth cohort. Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity. The effect of genetic differences and ovarian failure: intact cognitive function in adult women with premature ovarian failure versus turner syndrome. Cognitive performance in healthy women during induced hypogonadism and ovarian steroid addback. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Life course socioeconomic adversity and age at natural menopause in women from Latin America and the Caribbean. Cognitive functioning in elderly women who underwent unilateral oophorectomy before menopause. The next section reviews the choice of existing preparations, regimen, route of administration, dosage, and recommendations of treatment duration. The risk may be ameliorated by estrogen replacement therapy, but the quality of evidence is poor and limited to two studies. Bone health the beneficial effects of estrogen on bone health have long been recognized, and likewise the adverse effect of natural menopause on bone loss, mineral density and fracture risk (Ahlborg, et al. Estrogen has a major effect on both cortical and trabecular bone turnover through stimulatory effects on osteoblast and inhibitory effects on osteoclast differentiation, activity and cell survival (Manolagas, et al. In a group of 150 women with Turner syndrome (mean age 31 years) undergoing standardized multidisciplinary assessment, 12% were found to have osteoporosis, with a further 52% having osteopenia (Freriks, et al. Large, randomized trials have shown that estrogen therapy in postmenopausal women can improve bone mineral density and reduce vertebral and hip fracture risk (Wells, et al. Premature atherosclerosis (Clarkson, 2007), increased risk for non-procedurally-related venous thromboembolism (Canonico, et al. However, observational and non-randomised intervention studies have shown a decrease in myocardial infarction risk (Bain, et al. Adequate estrogen replacement should be ensured as estrogen is important for the health of the genito-urinary system, sexual function, and desire. The effect of different 108 treatments on neurological function in Turner Syndrome girls has been reported in several studies from the same research group. For women who underwent bilateral salpingo-oophorectomy before the onset of menopause, studies suggest that hormone treatment up to the age of 50 may be beneficial for neurological function (Sherwin, 1988; Phillips and Sherwin, 1992; Sherwin, 1994; Hogervorst and Bandelow, 2010). Estrogen replacement to reduce the possible risk of cognitive Neurological functionfi It has been reported that breast cancer risk increases with increasing age at menopause, and this risk seems lowest in women experiencing menopause before the age of 40 years (2012). In postmenopausal women, increased breast density, as assessed by mammography, is associated with increased breast cancer risk. They concluded that there was no statistically significant difference in breast density between the two groups (Soares, et al. The other study compared these mammography findings with 31 regularly menstruating age-matched controls and again found no statistically significant differences. While high breast density is associated with increased breast cancer risk, none of these women had an increase in breast density. Furthermore, none of these women were diagnosed with breast cancer or a benign breast disorder (Bosze, et al. A higher risk of breast cancer has been demonstrated with the continuous combined estrogen-progestogen regimen compared with the cyclical one, in several large cohort studies of postmenopausal women 110 (Lambrinoudaki, 2014). There has also been considerable debate on the effect of different progestins on the risk of breast cancer (Stahlberg, et al. In a recent review paper, it was suggested that the type of progestin may modulate breast cancer risk, with limited evidence supporting a favour for micronized progesterone over synthetic progestins (Davey, 2013). They conclude that the risks of regimens combining estrogens with continuous progestogens are not significantly different from placebo at two years (Furness, et al. Recommendation Progestogen should be given in combination with estrogen therapy to B protect the endometrium in women with an intact uterus. Patient preference is important for compliance and must therefore be taken into consideration when prescribing. Oral contraceptives contain the potent synthetic estrogen ethinylestradiol, which in effect provides more steroid hormone than is needed for physiologic replacement, with unfavourable effects on lipid profile, on haemostatic factors and with an increased risk of thromboembolic events related to the progestogen and first pass effect of the liver. Achieving an inadequate peak bone mass increases the risk of osteoporosis and bone fracture in later life. Other studies have shown that physiological sex steroid replacement with 17fi-estradiol has a beneficial effect on bone mass acquisition mediated by increased bone formation and decreased bone resorption. Progestogens Progesterone protects the endometrium from the mitogenic effect of estrogen, as discussed in Section 12. Synthetic progestogens provide effective endometrial protection and cycle control but should not be used for endometrial preparation for embryo transfer (Fatemi, et al. It appears to have a better cardiovascular safety profile when compared to synthetic progestogens (Mueck, 2012). Also, as described above, micronized natural progesterone may be preferred over synthetic progestogens with regard to breast cancer risk (Davey, 2013). Natural progesterone may have a more favourable cardiovascular profile and possibly a reduced risk of breast cancer. Some women using the combined oral contraceptive pill for estrogen replacement will be symptomatic during the pill-free (or inactive pill) week. Unopposed estrogen therapy is associated with an increased risk of endometrial hyperplasia after 1 to 3 years of treatment at all doses in postmenopausal women. Therefore, estrogen replacement in postmenopausal women with an intact uterus should always be supplemented with a progestogen to prevent endometrial hyperplasia and increased risk of malignant neoplasia (Furness, et al. Studies of menopausal women over 50 years of age have shown that supplementation with cyclical progestogen (progestogen for 10 days or more a month or 14 days up to every 12 weeks) lowers (but not eliminates) this risk, while continuous combined estrogen-progestogen therapy may even prevent endometrial hyperplasia and cancer (Furness, et al. The exact length of the cycle can be individualized to the patient, but probably should not be longer than 12-weeks to protect the endometrium from hyperplasia and malignant change. Some estrogen replacement regimens are protective against endometrial cancer in healthy women. Those 114 desiring a pregnancy may be better treated with a sequential regimen rather than a continuous combined one, even though the risk of endometrial hyperplasia/carcinoma may be slightly higher. Estrogen alone has the least influence on the breast tissue in postmenopausal women (Stefanick, et al. Subcutaneous implants and, more recently, nasal sprays and injectable estrogen preparations are also available, although not in all European countries. Local estrogen treatment can be administered in the form of an estrogen-releasing vaginal ring and estrogen-based vaginal creams and pessaries. Locally administered estrogen is mainly prescribed for genito-urinary symptoms (Suckling, et al. Compared to oral administration, the transdermal route can achieve higher plasma levels of circulating estradiol with a lower treatment dose and therefore fewer circulating estrogen metabolites, closer matching the normal premenopausal state (Goodman, 2012). There is a vast amount of data regarding the route-dependent effect of the metabolic actions of estrogen. Postmenopausal women over 50 years of age have a lower risk of myocardial infarction with transdermal estrogen compared with oral (Lokkegaard, et al. Also, breast density is less pronounced in postmenopausal women treated with transdermal preparations compared to oral (Goodman, 2012).

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