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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Medications for PCOS include oral contraceptives and metformin. The oral contraceptives increase sex hormone binding globulin production, which increases binding of free testosterone. This reduces the symptoms of hirsutism caused by high testosterone and regulates return to normal menstrual periods. Metformin is a drug commonly used in type 2 diabetes to reduce insulin resistance, and is used off label (in the UK, US, AU and EU) to treat insulin resistance seen in PCOS. In many cases, metformin also supports ovarian function and return to normal ovulation. Spironolactone can be used for its antiandrogenic effects, and the topical cream eflornithine can be used to reduce facial hair. A newer insulin resistance drug class, the thiazolidinediones (glitazones), have shown equivalent efficacy to metformin, but metformin has a more favorable side effect profile. The United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin when other therapy has failed to produce results. Metformin may not be effective in every type of PCOS, and therefore there is some disagreement about whether it should be used as a general first line therapy. The use of statins in the management of underlying metabolic syndrome remains unclear.
It can be difficult to become pregnant with PCOS because it causes irregular ovulation. Medications to induce fertility when trying to conceive include the ovulation inducer clomiphene or pulsatile leuprolide. Metformin improves the efficacy of fertility treatment when used in combination with clomiphene. Metformin is thought to be safe to use during pregnancy (pregnancy category B in the US). A review in 2014 concluded that the use of metformin does not increase the risk of major birth defects in women treated with metformin during the first trimester.
Although there are no approved pharmaceuticals for addressing female sexual disorders, several are under investigation for their effectiveness. A vacuum device is the only approved medical device for arousal and orgasm disorders. It is designed to increase blood flow to the clitoris and external genitalia. Women experiencing pain with intercourse are often prescribed pain relievers or desensitizing agents. Others are prescribed lubricants and/or hormone therapy. Many patients with female sexual dysfunction are often also referred to a counselor or therapist for psychosocial counseling.
When appropriate (e.g., in women of child-bearing age who require contraception), a standard contraceptive pill is frequently effective in reducing hirsutism. Progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.
Other drugs with anti-androgen effects include flutamide, and spironolactone, which can give some improvement in hirsutism. Metformin can reduce hirsutism, perhaps by reducing insulin resistance, and is often used if there are other features such as insulin resistance, diabetes, or obesity that should also benefit from metformin. Eflornithine (Vaniqa) is a drug that is applied to the skin in cream form, and acts directly on the hair follicles to inhibit hair growth. It is usually applied to the face. 5-alpha reductase inhibitors (such as finasteride and dutasteride) may also be used; they work by blocking the conversion of testosterone to dihydrotestosterone (the latter of which responsible for most hair growth alterations and androgenic acne).
Although these agents have shown significant efficacy in clinical trials (for oral contraceptives, in 60–100% of individuals), the reduction in hair growth may not be enough to eliminate the social embarrassment of hirsutism, or the inconvenience of plucking or shaving. Individuals vary in their response to different therapies. It is usually worth trying other drug treatments if one does not work, but drug treatments do not work well for all individuals.
Surgery is sometimes performed to alter the appearance of the genitals. However many surgeries performed on intersex people lack clear evidence of necessity, can be considered as mutilating, and are widely considered to be human rights violations when performed without the informed consent of the recipient.
Estrogens are responsible for the maintenance of collagen, elastic fibers, and vasoculature of the urogenital tract, all of which are important in maintaining vaginal structure and functional integrity; they are also important for maintaining vaginal pH and moisture levels, both of which aid in keeping the tissues lubricated and protected. Prolonged estrogen deficiency leads to atrophy, fibrosis, and reduced blood flow to the urogenital tract, which is what causes menopausal symptoms such as vaginal dryness and pain related to sexual activity and/or intercourse. It has been consistently demonstrated that women with lower sexual functioning have lower estradiol levels.
Androgen therapy for hypoactive sexual desire disorder (HSDD) has a small benefit but its safety is not known. It is not approved as a treatment in the United States. If used it is more common among women who have had an oophorectomy or who are in a postmenopausal state. However, like most treatments, this is also controversial. One study found that after a 24-week trial, those women taking androgens had higher scores of sexual desire compared to a placebo group. As with all pharmacological drugs, there are side effects in using androgens, which include hirutism, acne, ploycythaemia, increased high-density lipoproteins, cardiovascular risks, and endometrial hyperplasia is a possibility in women without hysterectomy. Alternative treatments include topical estrogen creams and gels can be applied to the vulva or vagina area to treat vaginal dryness and atrophy.
The genetic variation is irreversible, however, individuals who want to look more masculine can take testosterone. Treating adolescents with implants of controlled release testosterone has shown good results when appropriately monitored. Hormone therapy is also useful in preventing the onset of osteoporosis.
Often individuals that have noticeable breast tissue or hypogonadism experience depression and/or social anxiety because they are outside of social norms. An academic term for this is psychosocial morbidity. At least one study indicates that planned and timed support should be provided for young men with Klinefelter syndrome to ameliorate current poor psychosocial outcomes. The surgical removal of the breasts may be considered for both the psychological reasons and to reduce the risk of breast cancer.
The use of behavioral therapy can mitigate any language disorders, difficulties at school and socialization. An approach by occupational therapy is useful in children, especially those who have dyspraxia.
One possible treatment is with anastrozole. Histrelin acetate (Supprelin LA), triptorelin or leuprolide, any GnRH agonists, may be used. Non-continuous usage of GnRH agonists stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). However, when used regularly, GnRH agonists cause a decreased release of FSH and LH. Prolonged use has a risk of causing osteoporosis. After stopping GnRH agonists, pubertal changes resume within 3 to 12 months.
Upon diagnosis, estrogen and progesterone therapy is typically commenced, promoting the development of female characteristics.
The consequences of streak gonads to a person with Swyer syndrome:
1. Gonads cannot make estrogen, so the breasts will not develop and the uterus will not grow and menstruate until estrogen is administered. This is often given transdermally.
2. Gonads cannot make progesterone, so menstrual periods will not be predictable until progestin is administered, usually as a pill.
3. Gonads cannot produce eggs so conceiving children naturally is not possible. A woman with a uterus and ovaries but without female gamete is able to become pregnant by implantation of another woman's fertilized egg (embryo transfer).
4. Streak gonads with Y chromosome-containing cells have a high likelihood of developing cancer, especially gonadoblastoma. Streak gonads are usually removed within a year or so of diagnosis since the cancer can begin during infancy.
By 2010 over 100 successful pregnancies have been reported using IVF technology with surgically removed sperm material from males with Klinefelter syndrome. Microdissection testicular sperm extraction in adult men with Klinefelter syndrome reported success rates of up to 45%.
There is no known cure available for the Wilson-Turner Syndrome. Instead, treatment options are available to fight individual symptoms. For obesity, a nutritional diet manipulation is combined with an exercise regimen that has a greater energy expenditure than intake. For hypogonadism, testosterone replacement is done. Finally, for gynecomastia, weight loss using similar methods for obesity is prescribed. However, if the individual finds his increased breast tissue psychologically distressing and/or is too severe, reduction mammaplasty is done. Currently, researchers are investigating therapy using antiestrogens and aromatase inhibitors to treat persistent pubertal gynecomastia.
A few studies suggest that the antidepressant, bupropion, can improve sexual function in women who are not depressed, if they have HSDD. The same is true for the anxiolytic, buspirone, which is a 5-HT receptor agonist similarly to flibanserin.
Testosterone supplementation is effective in the short-term. However, its long-term safety is unclear.
Flibanserin is the first and only medication approved for women for the treatment of HSDD. It is only slightly effective over placebo, having been found to increase the average number of satisfying sexual events per month by 0.5 to 1. The side effects of dizziness, sleepiness, and nausea occur about three to four times more often. Overall improvement is slight to none.
Patients will generally need to be followed by an endocrinologist. If hypogonadism is present, testosterone treatment should be considered in all individuals regardless of cognitive abilities due to positive effects on bone health, muscle strength, fatigue, and endurance, with possible mental health/behavioral benefits as well.
Most children with XXYY will have some developmental delays and learning disabilities. Therefore the following aspects should be checked and monitored: psychology (cognitive and social–emotional development), speech/language therapy, occupational therapy, and physical therapy. Consultation with a developmental pediatrician, psychiatrist, or neurologist to develop a treatment plan including therapies, behavioral interventions, educational supports, and psychotropic medications for behavioral and psychiatric symptoms should be arranged.
Common diagnoses such as learning disability/ID, ADHD, autism spectrum disorders, mood disorders, tic disorders, and other mental health problems should be considered, screened for, and treated. Good responses to standard medication treatments for inattention, impulsivity, anxiety, and mood instability are seen in this group and such treatment can positively impact academic progress, emotional wellbeing and long-term outcome.
Poor fine motor coordination and the development of intention tremor can make handwriting slow and laborious, and occupational therapy and keyboarding should be introduced at an early age to facilitate schoolwork and self-help skills. Educational difficulties should be evaluated with a full psychological evaluation to identify discrepancies between verbal and performance skills and to identify individual academic needs. Expressive language skills are often affected throughout the lifespan and speech therapy interventions targeting expressive language skills, dyspraxia, and language pragmatics may be needed into adulthood. Adaptive skills (life skills) are a significant area of weakness necessitating community-based supports for almost all individuals in adulthood.
Additional treatment recommendations based on the individual strengths and weaknesses in XXYY syndrome may be required.
A number of medications have been used to treat vulvodynia. Evidence to support their use, however, is often poor. These include creams and ointments containing lidocaine, estrogen or tricyclic antidepressants. Antidepressants and anticonvulsants in pill form are sometimes tried but have been poorly studied. Injectable medications included steroids and botulinum toxin have been tried with limited success.
Botulinum toxin A (Botox) has been considered as a treatment option, under the idea of temporarily reducing the hypertonicity of the pelvic floor muscles. Although no random controlled trials have been done with this treatment, experimental studies with small samples have shown it to be effective, with sustained positive results through 10 months. Similar in its mechanism of treatment, lidocaine has also been tried as an experimental option.
Anxiolytics and antidepressants are other pharmacotherapies that have been offered to patients in conjunction with other psychotherapy modalities, or if these patients experience high levels of anxiety from their condition. Results from these types of pharmacologic therapies have not been consistent.
The consequences to the girl with XX gonadal dysgenesis:
1. Her gonads cannot make estrogen, so her breasts will not develop and her uterus will not grow and menstruate until she is given estrogen. This is often given through the skin now.
2. Her gonads cannot make progesterone, so her menstrual periods will not be predictable until she is given a progestin, still usually as a pill.
3. Her gonads cannot produce eggs so she will not be able to conceive children naturally. A woman with a uterus but no ovaries may be able to become pregnant by implantation of another woman's fertilized egg (embryo transfer).
Treatment is often started without confirmation of infection because of the serious complications that may result from delayed treatment. Treatment depends on the infectious agent and generally involves the use of antibiotic therapy. If there is no improvement within two to three days, the patient is typically advised to seek further medical attention. Hospitalization sometimes becomes necessary if there are other complications. Treating sexual partners for possible STIs can help in treatment and prevention.
For women with PID of mild to moderate severity, parenteral and oral therapies appear to be effective. It does not matter to their short- or long-term outcome whether antibiotics are administered to them as inpatients or outpatients. Typical regimens include cefoxitin or cefotetan plus doxycycline, and clindamycin plus gentamicin. An alternative parenteral regimen is ampicillin/sulbactam plus doxycycline. Erythromycin-based medications can also be used. Another alternative is to use a parenteral regimen with ceftriaxone or cefoxitin plus doxycycline. Clinical experience guides decisions regarding transition from parenteral to oral therapy, which usually can be initiated within 24–48 hours of clinical improvement.
Often, when faced with a person experiencing painful intercourse, a gynecologist will recommend Kegel exercises and provide some additional lubricants. Strengthening the muscles that unconsciously tighten during vaginismus may be extremely counter-intuitive for some people. Although vaginismus has not been shown to affect a person's ability to produce lubrication, providing additional lubricant can be helpful in achieving successful penetration. This is due to the fact that women may not produce natural lubrication if anxious or in pain. Treatment of vaginismus may involve the use Hegar dilators, (sometimes called vaginal trainers) progressively increasing the size of the dilator inserted into the vagina.
There are a number of possible treatments with none being uniformly effective. Treatments include:
The treatment of genetic disorders is an ongoing battle with over 1800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating the symptoms of the disorders in an attempt to improve patient quality of life.
Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of disease. A major obstacle has been the delivery of genes to the appropriate cell, tissue, and organ affected by the disorder. How does one introduce a gene into the potentially trillions of cells which carry the defective copy? This question has been the roadblock between understanding the genetic disorder and correcting the genetic disorder.
Treatment includes androgen (testosterone) supplementation to artificially initiate puberty, testicular prosthetic implantation, and psychological support. Gender Dysphoria may result in anorchic individuals who are assigned male at birth and raised as male despite lacking the necessary masculinizing hormones during prenatal, childhood, and adolescent development. Anorchic individuals who have a female identity may be administered estrogen alone in place of testosterone as no androgen blockers are necessary due to the lack of gonads.
46,XX testicular disorders of sex development (46,XX DSD) describes a condition in which individuals with two X chromosomes in each cell, the pattern typically found in females, have a male phenotype appearance. 46,XX testicular disorders of sex development may also be named 46,XX sex reversal, nonsyndromic 46,XX testicular DSD, XX male syndrome, and XX sex reversal.
At puberty, most affected individuals require treatment with the male sex hormone testosterone to induce development of male secondary sex characteristics such as facial hair and deepening of the voice (masculinization). Hormone treatment can also help prevent breast enlargement (gynecomastia). Adults with this disorder are usually shorter than average for males and are unable to have children (infertile).
Psychosexual disorders can vary greatly in severity and treatability. Medical professionals and licensed therapists are necessary in diagnosis and treatment plans. Treatment can vary from therapy to prescription medication. Sex therapy, behavioral therapy, and group therapy may be helpful to those suffering distress from sexual dysfunction. More serious sexual perversions may be treated with androgen blockers or selective serotonin reuptake inhibitors (SSRIs) to help restore hormonal and neurochemical balances.
Treatment depends on diagnosis and may include hormonal therapy, iv fluids, blood transfusion, and/or a dilation and curettage. Internal bleeding requires laparoscopy or abdominal surgery, in rare and extreme cases a hysterectomy is performed.