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The treatment of anovulation is termed ovulation induction and is usually quite efficient. The main treatments are clomifene citrate and gonadotropins.
Clomifene citrate (or clomid) is the medication which is most commonly used to treat anovulation. It is a selective estrogen-receptor modulator, affecting the hypothalamic–pituitary–gonadal axis to respond as if there was an estrogen deficit in the body, in effect increasing the production of gonadotrophins. It is relatively easy and convenient to use. Clomifene appears to inhibit estrogen receptors in hypothalamus, thereby inhibiting negative feedback of estrogen on gonadotrophin production. It may also result in direct stimulation of the hypothalamic-pituitary axis. It also has an effect on cervical mucus quality and uterine mucosa, which might affect sperm penetration and survival, hence its early administration during the menstrual cycle. Clomifene citrate is a very efficient ovulation inductor, and has a success rate of 67%. Nevertheless, it only has a 37% success rate in inducing pregnancy. This difference may be due to the anti-estrogenic effect which clomifene citrate has on the endometrium, cervical mucus, uterine blood flow, as well as the resulting decrease in the motility of the fallopian tubes and the maturation of the oocytes.
The standard dosage for first-time takers is 50 or 100 mg of clomifene per day for five consecutive days, starting early in the menstrual cycle, usually on the third to fifth day counting from the beginning of the menstrual period. In case of amenorrhea, a period can be induced by intake of an oral progestin for 10 days. In absence of success, the dosage can be increased in subsequent cycles with increments of 50 mg. However, at a dosage of 200 mg, further increments are unlikely to increase pregnancy chances.
SERMs are a category of drugs, either synthetically produced or derived from a botanical source, that act selectively as agonists or antagonists on the estrogen receptors throughout the body. The most commonly prescribed SERMs are raloxifene and tamoxifen. Raloxifene exhibits oestrogen agonist activity on bone and lipids, and antagonist activity on breast and the endometrium. Tamoxifen is in widespread use for treatment of hormone sensitive breast cancer. Raloxifene prevents vertebral fractures in postmenopausal, osteoporotic women and reduces the risk of invasive breast cancer.
Some of the SSRIs and SNRIs appear to provide some relief. Low dose paroxetine has been FDA-approved for hot moderate-to-severe vasomotor symptoms associated with menopause. They may, however, be associated with sleeping problems.
Gabapentin or clonidine may help but does not work as well as hormone therapy. Clonidine may be associated with constipation and sleeping problems.
Treatments vary based on the underlying condition. Key issues are problems of surgical correction if appropriate and oestrogen therapy if oestrogen levels are low. For those who do not plan to have biological children, treatment may be unnecessary if the underlying cause of the amenorrhoea is not threatening to their health. However, in the case of athletic amenorrhoea, deficiencies in estrogen and leptin often simultaneously result in bone loss, potentially leading to osteoporosis.
"Athletic" amenorrhoea which is part of the female athlete triad is treated by eating more and decreasing the amount and intensity of exercise. If the underlying cause is the athlete triad then a multidisciplinary treatment including monitoring from a physician, dietitian, and mental health counselor is recommended, along with support from family, friends, and coaches. Although oral contraceptives can causes menses to return, oral contraceptives should not be the initial treatment as they can mask the underlying problem and allow other effects of the eating disorder, like osteoporosis, continue to develop. Weight recovery, or increased rest does not always catalyze the return of a menses. Recommencement of ovulation suggests a dependency on a whole network of neurotransmitters and hormones, altered in response to the initial triggers of secondary amenorrhoea. To treat drug-induced amenorrhoea, stopping the medication on the advice of a doctor is a usual course of action.
Looking at Hypothalamic amenorrhoea, studies have provided that the administration of a selective serotonin reuptake inhibitor (SSRI) might correct abnormalities of Functional Hypothalamic Amenorrhoea (FHA) related to the condition of stress-related amenorrhoea. This involves the repair of the PI3K signaling pathway, which facilitates the integration of metabolic and neural signals regulating gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH). In other words, it regulates the neuronal activity and expression of neuropeptide systems that promote GnRH release. However, SSRI therapy represents a possible hormonal solution to just one hormonal condition of hypothalamic amenorrhoea. Furthermore, because the condition involves the inter workings of many different neurotransmitters, much research is still to be done on presenting hormonal treatment that would counteract the hormonal affects.
As for physiological treatments to hypothalamic amenorrhoea, injections of metreleptin (r-metHuLeptin) have been tested as treatment to oestrogen deficiency resulting from low gonadotropins and other neuroendocrine defects such as low concentrations of thyroid and IGF-1. R-metHuLeptin has appeared effective in restoring defects in the hypothalamic-pituitary-gonadal axis and improving reproductive, thyroid, and IGF hormones, as well as bone formation, thus curing the amenorrhoea and infertility. However, it has not proved effective in restoring of cortisol and adrenocorticotropin levels, or bone resorption.
These have been ranked by the UK's National Institute for Health and Clinical Excellence:
- First line
- Intrauterine device with progesterone
- Second Line
- Tranexamic acid an antifibrinolytic agent
- Nonsteroidal anti-inflammatory drugs (NSAIDs).
- Combined oral contraceptive pills to prevent proliferation of the endometrium
- Third line
- Oral progestogen (e.g. norethisterone), to prevent proliferation of the endometrium
- Injected progestogen (e.g. Depo provera)
- Other options
- Gonadotropin-releasing hormone agonist
A review indicated the effectiveness of transdermal nitroglycerin.
Where an underlying cause can be identified, treatment may be directed at this. Clearly heavy periods at menarche and menopause may settle spontaneously (the menarche being the start and menopause being the cessation of periods).
If the degree of bleeding is mild, all that may be sought by the woman is the reassurance that there is no sinister underlying cause. If anemia occurs due to bleeding then iron tablets may be used to help restore normal hemoglobin levels.
The condition is often treated with hormones, particularly as abnormal uterine bleeding commonly occurs in the early and late menstrual years when contraception is also sought. Usually, oral combined contraceptive or progesterone only pills may be taken for a few months, but for longer-term treatment the alternatives of injected Depo Provera or the more recent progesterone releasing IntraUterine System (IUS) may be used. Fibroids may respond to hormonal treatment, and if they do not, then surgical removal may be required.
Tranexamic acid tablets that may also reduce loss by up to 50%. This may be combined with hormonal medication previously mentioned.
Anti-inflammatory medication like NSAIDs may also be used. NSAIDs are the first-line medications in ovulatory menorrhagia, resulting in an average reduction of 20-46% in menstrual blood flow. For this purpose, NSAIDs are ingested for only 5 days of the menstrual cycle, limiting their most common adverse effect of dyspepsia.
A definitive treatment for menorrhagia is to perform hysterectomy (removal of the uterus). The risks of the procedure have been reduced with measures to reduce the risk of deep vein thrombosis after surgery, and the switch from the front abdominal to vaginal approach greatly minimizing the discomfort and recuperation time for the patient; however extensive fibroids may make the womb too large for removal by the vaginal approach. Small fibroids may be dealt with by local removal (myomectomy). A further surgical technique is endometrial ablation (destruction) by the use of applied heat (thermoablation).
In the UK the use of hysterectomy for menorrhagia has been almost halved between 1989 and 2003. This has a number of causes: better medical management, endometrial ablation and particularly the introduction of IUS which may be inserted in the community and avoid the need for specialist referral; in one study up to 64% of women cancelled surgery.
Drug of choice is progesterone.
Management of dysfunctional uterine bleeding predominantly consists of reassurance, though mid-cycle estrogen and late-cycle progestin can be used for mid- and late-cycle bleeding respectively.
Also, non-specific hormonal therapy such as combined high-dose estrogen and high-dose progestin can be given. Ormeloxifene is a non-hormonal medication that treats DUB but is only legally available in India.
The goal of therapy should be to arrest bleeding, replace lost iron to avoid anemia, and prevent future bleeding.
Excessive movement before any treatments or surgeries will cause excessive bleeding.
A hysterectomy may be performed in some cases.
Use of hormonal birth control may improve symptoms of primary dysmenorrhea. A 2009 systematic review however found limited evidence that the birth control pill, containing low doses or medium doses of oestrogen, reduces pain associated with dysmenorrhea. In addition, no differences between different birth control pill preparations were found.
Norplant and Depo-provera are also effective, since these methods often induce amenorrhea. The intrauterine system (Mirena IUD) may be useful in reducing symptoms.
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.
If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill. The purpose of regulating menstruation, in essence, is for the woman's convenience, and perhaps her sense of well-being; there is no medical requirement for regular periods, as long as they occur sufficiently often.
If a regular menstrual cycle is not desired, then therapy for an irregular cycle is not necessarily required. Most experts say that, if a menstrual bleed occurs at least every three months, then the endometrium (womb lining) is being shed sufficiently often to prevent an increased risk of endometrial abnormalities or cancer. If menstruation occurs less often or not at all, some form of progestogen replacement is recommended. An alternative is oral progestogen taken at intervals (e.g., every three months) to induce a predictable menstrual bleeding.
The pain is not harmful and does not signify the presence of disease. No treatment is usually necessary. Pain relievers (analgesics) may be needed in cases of prolonged or intense pain.
Hormonal forms of contraception can be taken to prevent ovulation—and therefore ovulatory pain—but otherwise there is no known prevention.
Medicinal and surgical interventions produce roughly equivalent pain-relief benefits. Recurrence of pain was found to be 44 and 53 percent with medicinal and surgical interventions, respectively. Each approach has advantages and disadvantages. Manual therapy showed a decrease in pain for 84 percent of study participants, and a 93 percent improvement in sexual function.
Evidence on how effective medication is for relieving pain associated with endometriosis is limited.
The advantages of surgery are demonstrated efficacy for pain control, it is more effective for infertility than medicinal intervention, it provides a definitive diagnosis, and surgery can often be performed as a minimally invasive (laparoscopic) procedure to reduce morbidity and minimize the risk of post-operative adhesions. Efforts to develop effective strategies to reduce or prevent adhesions have been undertaken, but their formation remain a frequent side effect of abdominal surgery.
The advantages of physical therapy techniques are decreased cost, absence of major side-effects, it does not interfere with fertility, and near-universal increase of sexual function. Disadvantages are that there are no large or long-term studies of its use for treating pain or infertility related to endometriosis.
The overall effectiveness of manual physical therapy to treat endometriosis has not yet been identified. There is no evidence to support nutritional therapy as effective.
Certain medications, particularly contraceptive medications, can induce amenorrhoea in a healthy woman. The lack of menstruation usually begins shortly after beginning the medication and can take up to a year to resume after stopping a medication. Hormonal contraceptives that contain only progestogen like the oral contraceptive Micronor, and especially higher-dose formulations like the injectable Depo Provera commonly induce this side-effect. Extended cycle use of combined hormonal contraceptives also allow suppression of menstruation. Patients who use and then cease using contraceptives like the combined oral contraceptive pill may experience secondary amenorrhoea as a withdrawal symptom. The link is not well understood, as studies have found no difference in hormone levels between women who develop amenorrhoea as a withdrawal symptom following the cessation of OCOP use and women who experience secondary amenorrhoea because of other reasons. New contraceptive pills, like continuous oral contraceptive pills (OCPs) which do not have the normal 7 days of placebo pills in each cycle, have been shown to increase rates of amenorrhoea in women. Studies show that women are most likely to experience amenorrhoea after 1 year of treatment with continuous OCP use.
The use of opiates (such as heroin) on a regular basis has also been known to cause amenorrhoea in longer term users.
Anti-psychotic drugs used to treat schizophrenia have been known to cause amenorrhoea as well. New research suggests that adding a dosage of Metformin to an anti-psychotic drug regimen can restore menstruation. Metformin decreases resistance to the hormone insulin, as well as levels of prolactin, testosterone, and lutenizing hormone (LH). Metformin also decreases the LH/FSH ratio. Results of the study on Metformin further implicate the regulation of these hormones as a main cause of secondary amenorrhoea.
Women charting with some form of fertility awareness may find mittelschmerz to be a helpful secondary sign in detecting ovulation. Because normal sperm life is up to five days, however, mittelschmerz alone does not provide sufficient advance warning to avoid pregnancy. Because other causes of minor abdominal pain are common, mittelschmerz alone also cannot be used to confirm the beginning of the post-ovulatory infertile period.
Treatment of hyperandrogenism varies with the underlying condition that causes it. As a hormonal symptom of polycystic ovary syndrome, menopause, and other endocrine disorders, it is primarily treated as a symptom of these disorders. Systemically, it is treated with antiandrogens such as cyproterone acetate, flutamide and spironolactone to control the androgen levels in the patient's body. For Hyperandrogenism caused by Late-Onset Congenital Adrenal Hyperplasia (CAH), treatment is primarily focused on providing the patient with Glucocorticoids to combat the low cortisol production and the corresponding increase in androgens caused by the swelling of the Adrenal Glands. Oestrogen-based oral contraceptives are used to treat both CAH and PCOS caused hyperandrogenism. These hormonal treatments have been found to reduce the androgen excess and suppress adrenal androgen production and cause a significant decrease in hirsutism.
Hyperandrogenism is often managed symptomatically. Hirsutism and acne both respond well to the hormonal treatments described above, with 60-100% reporting an improvement in hirsutism. Androgenic alopecia however, does not show a significant improvement with hormonal treatments and requires other treatments, such as hair transplantation.
Treatment may consist of surgery in the case of tumors, lower doses of estrogen in the case of exogenously-mediated estrogen excess, and estrogen-suppressing medications like gonadotropin-releasing hormone analogues and progestogens. In addition, androgens may be supplemented in the case of males.
Pain associated with ovarian cysts may be treated in several ways:
- Pain relievers such as acetaminophen, nonsteroidal anti-inflammatory drugs, or opioids.
- While hormonal birth control prevents the development of new cysts in those who frequently get them, it is not useful for the treatment of current cysts.
Since risk factors are not known and vary among individuals with hyperandrogegism, there is no sure method to prevent this medical condition. Therefore, more longterm studies are needed first to find a cause for the condition before being able to find a sufficient method of prevention.
However, there are a few things that can help avoid long-term medical issues related to hyperandrogenism like PCOS. Getting checked by a medical professional for hyperandrogenism; especially if one has a family history of the condition, irregular periods, or diabetes; can be beneficial. Watching your weight and diet is also important in decreasing your chances, especially in obese females, since continued exercise and maintaining a healthy diet leads to an improved menstrual cycle as well as to decreased insulin levels and androgen concentrations.
Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen.
Treatment depends on the type of ovary apoplexy and the severity of intra-abdominal bleeding, but the condition must be treated in a hospital. In the case of pain without signs of intraabdominal bleeding, conservative therapy may be initiated, which includes bed rest, antispasmodics, and physiotherapy. In the presence or suspected internal bleeding, surgery is indicated via laparoscopy or laparotomy. Other treatments may include efforts to stop the bleeding or resection of the affected portion of the ovary. However, in cases in which there is extensive damage to the ovary, it may be necessary to remove it.
After being discharged from the hospital, it is important to take steps to prevent a recurrence in the future. Such steps include avoiding risk factors or beginning a regimen of oral contraceptives to control ovarian activity.
SSRIs like fluoxetine, sertraline can be used to treat severe PMS. Women with PMS may be able to take medication only on the days when symptoms are expected to occur. Although intermittent therapy might be more acceptable to some women, this might be less effective than continuous regimens. Side effect such as nausea and weakness are however relatively common.
As endosalpingiosis, generally, is not considered a pathology, treatment is not always necessary. However the treatment of other problems caused by this condition, such as ovarian cysts, chocolate cysts, fertility, pelvic pain, adhesions, dyspareunia may need to be addressed depending on the case.
Similar to Endometriosis, cases of endosalpingiosis that cause significant amounts of pain can be treated with excision surgery by a specialist, though this is not a cure. Removal of the tissues, cysts, and adhesions can help to greatly reduce symptoms. Some surgeons believe add-back therapy with progesterone to also be helpful in reducing symptoms. Taking progesterone continuously keeps a woman at a specific time in her menstrual cycle. This prevents the body from reaching high levels of estrogen found in ovulation and further aggravating the condition. Dietary estrogen can wreak havoc in highly sensitive cases, and similar to endometriosis women are encouraged to eat diets low in estrogens. This means avoiding foods like soy, black liquorice, and tofu, to name a few.