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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.
The treatment of anovulation is termed ovulation induction and is usually quite efficient. The main treatments are clomifene citrate and gonadotropins.
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.
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.
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.
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.
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.
Male primary or hypergonadogropic hypogonadism is often treated with testosterone replacement therapy if they are not trying to conceive. Adverse effects of testosterone replacement therapy include increased cardiovascular events (including strokes and heart attacks) and death. The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.
Commonly used testosterone replacement therapies include transdermal (through the skin) using a patch or gel, injections, or pellets. Oral testosterone is no longer used in the U.S. because it is broken down in the liver and rendered inactive; it also can cause severe liver damage. Like many hormonal therapies, changes take place over time. It may take as long as 2–3 months at optimum level to reduce the symptoms, particularly wordfinding and cognitive dysfunction. Testosterone levels in the blood should be evaluated to ensure the increase is adequate. Levels between 400 and 700 ng/dL are considered appropriate mid-dose levels. Treatment usually starts with 200 mg intramuscular testosterone, repeated every 14 days.
While historically, men with prostate cancer risk were warned against testosterone therapy, that has shown to be a myth.
Other side effects can include an elevation of the hematocrit to levels that require blood withdrawal (phlebotomy) to prevent complications from excessively thick blood. Gynecomastia (growth of breasts in men) sometimes occurs. Finally, some physicians worry that obstructive sleep apnea may worsen with testosterone therapy, and should be monitored.
Another treatment for hypogonadism is human chorionic gonadotropin (hCG). This stimulates the LH receptor, thereby promoting testosterone synthesis. This will not be effective in men who simply cannot make testosterone anymore (primary hypogonadism) and the failure of hCG therapy is further support for the existence of true testicular failure in a patient. It is particularly indicated in men with hypogonadism who wish to retain their fertility, as it does not suppress spermatogenesis like testosterone replacement therapy does.
For both men and women, an alternative to testosterone replacement is low-dose clomifene treatment, which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects that can result from direct hormone replacement therapy. This therapy has only been shown helpful for men with secondary hypogonadism. Recent studies have shown it can be safe and effective monotherapy for up to 2 years in patients with intact testicular function and impaired function of the HPTA(http://www.nature.com/ijir/journal/v15/n3/full/3900981a.html). Clomifene blocks estrogen from binding to some estrogen receptors in the hypothalamus, thereby causing an increased release gNRH and subsequently LH from the pituitary. Clomifene is a Selective Estrogen Reuptake Modulator (SERM).
Generally clomifene does not have adverse effects at the doses used for this purpose. Clomifene at much higher doses is used to induce ovulation and has significant adverse effects in such a setting.
For women with hypogonadism, estradiol and progesterone are often replaced. Some types of fertility defects can be treated, others cannot. Some physicians also give testosterone to women, mainly to increase libido.
Exercise amenorrhoea can be managed by eating a diet rich in calories and by decreasing the duration and intensity of exercise for at least 12 months. Amenorrhea usually persists and may take over 6 months to reverse .
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.
A review indicated the effectiveness of transdermal nitroglycerin.
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.
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.
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 is usually medication with dopamine agonists such as cabergoline, bromocriptine (often preferred when pregnancy is possible), and less frequently lisuride. A new drug in use is norprolac with the active ingredient quinagolide. Terguride is also used.
"Vitex agnus-castus" extract can be tried in cases of mild hyperprolactinaemia.
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.
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.
While there is no cure for endometriosis, there are two types of interventions; treatment of pain and treatment of endometriosis-associated infertility. In many women menopause (natural or surgical) will abate the process. In women in the reproductive years, endometriosis is merely managed: the goal is to provide pain relief, to restrict progression of the process, and to restore or preserve fertility where needed. In younger women, surgical treatment attempts to remove endometrial tissue and preserve the ovaries without damaging normal tissue.
In general, the diagnosis of endometriosis is confirmed during surgery, at which time ablative steps can be taken. Further steps depend on circumstances: a woman without infertility can be managed with hormonal medication that suppresses the natural cycle and pain medication, while an infertile woman may be treated expectantly after surgery, with fertility medication, or with IVF. As to the surgical procedure, ablation (or fulguration) of endometriosis (burning and vaporizing the lesions with an electric device) has shown a high rate of short-term recurrence after the procedure. The best surgical procedure with much lower rate of short-term recurrence is to excise (cut and remove) the lesions completely.
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.
Danazol, an estrogen biosynthesis inhibitor, tamoxifen, an antagonistic modulator of the estrogen receptor, and bromocriptine, a prolactin-lowering D receptor agonist, are the main drugs used in the treatment of mastodynia and are effective.
Other medications and supplements have been found to be of benefit. Spironolactone (Aldactone), low dose oral contraceptives, low-dose estrogen have helped to relieve pain. Topical anti-inflammatory medications can be used for localized pain. For anti hormonal treatment, danazol (Danocrine) can be helpful. Tamoxifen citrate is used in some cases of severe breast pain. Vitamin E is not effective in relieving pain nor is Evening primrose oil. Vitamin B and Vitamin A have not been consistently found to be beneficial. Flaxseed has shown some activity in the treatment of cyclic mastalgia.
Pain may be relieved by the use of nonsteroidal anti-inflammatory drugs or, for more severe localized pain, by local anaesthetic. Pain may be relieved psychologically by reassurance that it does not signal a serious underlying problem, and an active life style can also effect an improvement.
Information regarding how the pain is real but not necessarily caused by disease can help to understand the problem. Learning breast self-examination helps to orient the woman to normal and expected texture and structure of the breast and nipple. Yearly breast exams may be suggested. Counseling can also be to describe changes that vary during the monthly cycle. Women on hormone replacement therapy may benefit from a dose adjustment. Another non-pharmacological measure to help relieve symptoms of pain may be to use good bra support. Breasts change during adolescence and menopause and refitting may be beneficial. Applying heat and/or ice can bring relief. Dietary changes may also help with the pain. Methylxanthines can be eliminated from the diet to see if a sensitivity is present. Some clinicians recommending a reduction in salt, though no evidence supports this practice.
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.
Pseudocyesis is not known to have a direct underlying physical cause and there are no general recommendations regarding treatment with medications. In some cases, however, the patient may be given medications for such symptoms as the cessation of menstruation. When some patients with pseudocyesis have underlying psychological problems, they should be referred to a psychotherapist for the treatment of these problems. It is important at the same time, however, for the treating professional not to minimize the reality of the patient's physical symptoms. The treatment that has had the most success is demonstrating to the patient that she is not really pregnant by the use of ultrasound or other imaging techniques.
A menstrual disorder is an abnormal condition in a woman's menstrual cycle.