Introduction
Polycystic Ovary Syndrome (PCOS) is a serious endocrine system disorder that affects the normal functioning of ovaries in women who have attained the age of childbearing (Balen, Conway, Homburg, & Legro 2005). According to statistics released by the World Health Organization (WHO), this disorder has been reported in more than 5 million women in the United States alone. Globally, it affects between 5 and 10% of women who have attained the childbearing age. The disorder can have adverse effects on a woman’s menstrual cycle, hormones, blood vessels, heart, appearance, and ability to bear children (Homburg 2001). It is characterized by high levels of androgens, missed or irregular periods, and the presence of numerous small cysts in the ovaries. The cause of the disorder is unknown although scientists attribute it to factors such as genetics, hormonal imbalance, and heredity. Major symptoms include acne, anxiety or depression, irregular periods, infertility, cysts on the ovaries, pelvic pain, male-pattern baldness, hirsutism, skin tags, and sleep apnea (Homburg 2001). Research has established that these symptoms can show as early as during late teenage for some women. In addition, PCOS increases the vulnerability of women to chronic health conditions such as diabetes and high cholesterol levels (Radosh 2009). Treatments for PCOS include lifestyle modification, birth control pills, diabetes medications, fertility medications, surgery, and drugs for increased hair growth (Balen et al. 2005). This paper will discuss the pharmacological management of PCOS and outline its treatment guidelines.
Pharmacological management of PCOS
The pharmacological management of PCOS involves the use of drugs that target specific manifestations and individualized patient goals. In that regard, doctors usually prescribe medications that regulate the menstrual cycle, enhance ovulation, reduce excessive hair growth, and clear certain symptoms (Balen et al. 2005). Different medications are used to treat manifestations such as hirsutism, infertility, insulin resistance, and menstrual irregularities. Few agents have been approved by the Food and Drug Administration (FDA) for use in the treatment of PCOS. The choice of drug to use is primarily determined by comorbidities and the patient’s desire for pregnancy (Homburg 2001). Insulin-sensitizing agents are usually prescribed because they successfully control or manage menstrual irregularities, hirsutism, anovulation, insulin resistance, and obesity (Radosh 2009). Treatment should be individualized and address the specific manifestations of PCOS present in the patient.
Drugs for various PCOS manifestations
As mentioned earlier, successful management of PCOS involves the prescription of specific agents to clear various manifestations of the disease such as hirsutism, obesity, insulin resistance, and infertility (Radosh 2009). In each treatment regimen, there are first-line agents that have been approved by the FDA for the treatment of PCOS. Pharmacological management of PCOS targets the manifestations of the disorder such as menstrual irregularity, metabolic derangements, anovulation, and hirsutism (Balen et al. 2005). The recommendation to use insulin-sensitizing drugs is based on their ability to lower the levels of androgens, enhance ovulation rate, and increase tolerance to glucose. First-line treatment usually includes the administration of an oral contraceptive to initiate menstruation (Radosh 2009). The drug serves two functions namely cessation of the production of ovarian androgen and enhancement of the production of Sex Hormone-Binding Globulin (SHBG).
Guidelines and key recommendations
In 2013, the Endocrine Society released guidelines that were aimed at guiding medical practitioners with regard to the diagnosis and treatment of PCOS. Hormonal contraceptives are recommended as first-line treatment agents for women with manifestations of hirsutism and menstrual abnormalities (Radosh 2009). Clomiphene is recommended as the first-line treatment agent for infertility while metformin is recommended for improving menstrual and metabolic/glycemic abnormalities (Balen et al. 2005). The guidelines state that metformin is ineffective in the management of hirsutism, acne, and infertility. According to the American College of Obstetricians and Gynecologists (ACOG) and Society of Obstetricians and Gynecologists of Canada (SOGC), clomiphene citrate is the best agent for the treatment of PCOS with regard to manifestations of infertility (Ndefo, Eaton, & Green 2013). The second-line treatment is the use of gonadotropins or the application of surgery. In case gonadotropins are used, the physician should develop a low-dosage treatment program for the patient. Several studies have validated the claim that metformin s an effective medication in the enhancement of ovulation rates among women with PCOS (Balen et al. 2005). In addition, they have shown that it improves the efficiency of clomiphene with regard to the induction of ovulation. This combination is highly recommended when treating older women who show resistance to clomiphene or who have visceral obesity.
The most common first-line agents include metformin, clomiphene, eflornithine, oral contraceptives, pioglitazone, rosiglitazone, and spironolactone (Homburg 2001). On the other hand, second-line agents include acarbose (150 mg per day), desogestrel/ethinly estradiol (0.15 my per day and 30 mcg ethinly estardiol per day), finasteride, flutamide (formerly Eulexin) (250 mg once or twice per day), letrozole (2.5 mg per day), and sibutramine (10 mg per day). First-line agents for treatment of hirsutism include spironolactone, metformin, and eflornithine. First-line agents for initiation of ovulation include metformin and Clomiphene (Homburg 2001). In addition, the two agents can be combined to improve their effectiveness. Metformin, rosiglitazone, and pioglitazone improve insulin resistance (Balen et al. 2005). In cases of obese patients, metformin is recommended as the first-line agent.
Hirsutism
Treatment for hirsutism is executed using several medications. First-line agents for the treatment of hirsutism in patients with PCOS include spironolacone (Aldactone), metformin, and eflornithine (Vaniqa). The dosage for eflornithine involves the use of 13.9% cream that is applied to the face twice every day while that of metformin is 1,500 to 2, 250 mg every day. Some physicians also prescribe combinations of different oral contraceptives that contain progestins of drospirenone, norgestimate, and desogestrel (Homburg 2001). The dosage for oral contraceptives varies based on the physician’s recommendations and assessment. These combinations are not commonly used because they have not yet received approval from the FDA. A study to evaluate the effectiveness of such combination drugs found out that women whose prescriptions included combinations of desogestrel and Apri reported lower hirsutism scores on a Ferriman-Gallwey hirsutism score (Balen et al. 2005). Other medications that are effective for treatment of hirsutism include finasteride (Propecia) and flutamide (Eulexin). The dosage for finasteride is 5 mg per day while that for flutamide is 250 mg administered once or twice a day based on the recommendations of a doctor (Radosh 2009). However, they are not commonly used because they have been given a very low classification by the FDA and therefore, they are not recommended. Spironolactone is highly effective because it possesses antiandrogenic features (Homburg 2001). However, it is rarely used because it has not yet been approved by the FDA. Its recommended dosage is between 50 and 200 mg per day.
Several studies have proved that this medication is highly efficacious. In certain cases, spironolactone can be combined together with oral contraceptives (Mukherjee 2012). However, great caution should be taken because certain agents can lead to hyperkalemia. Examples of other medications that treat hirsutism include insulin-sensitizing agents such as acarbose and metformin. For many years, metformin was believed to be as effective as oral contraceptives in the treatment of PCO. However, recent systematic studies have found out that it is not as effective as previously believed to be (Mukherjee 2012). The FDA has approved an agent known as topical eflornithine for the elimination of excess facial hair. On the other hand, sibutramine has been approved form the management of obesity and studies have found that it can also be applied in the management of hirsutism (Homburg 2001).
Antiandrogens such as spironolactone, flutamide, and finasteride decrease the levels of androgens and therefore, reduce the manifestations of acne and hirsutism. In addition, the also increase the levels of lipids in the body. A study aimed at studying the effectiveness of spironolactone, finasteride, and flutamide found out that the three drugs are efficacious in the treatment of hirsutism and acne in women with acne (Balen et al. 2005). Participants were administered with 100mg of spironolactone, 5 mg of finasteride, and 250 mg of finasteride every day. The most commonly used drug is spironolactone. The recommended dosage is 25 to 100 mg administered twice every day (Mukherjee 2012). The drug is safe, readily available, and cheap compared to the other two. Women with manifestations of hirsutism who do not wish to become pregnant should use oral contraceptives. The major oral contraceptives sued include a combination of estrogen and progestin drugs (Homburg 2001). Some studies have suggested that oral contraceptives can be combined with antiandrogens for better health outcomes.
Infertility
Deviances in hormonal secretion and function in women with polycystic ovary syndrome can alter the normal menstrual cycle and cause irregularities such as oligomenorrhea and amenorrhea (Mukherjee 2012). These irregularities can lead to abnormalities such as uterine bleeding and infertility. Medications used as first-line treatment agents include metformin, clomiphene. These gents induce ovulation and treat infertility. Clomiphene can be used alone or can be combined with other agents (Balen et al. 2005). Clomiphene citrate is the most preferred drug to induce ovulation. The initial stage of treatment involves the administration of a dose of 50 mg/day for 5 consecutive days. This same dose is given if after the first time ovulation occurs but does not lead to pregnancy. Lack of ovulation after the first cycle of treatment, the does is increased. The second treatment cycle includes a dose of 100 grams for 5 consecutive days administered one month after the first treatment (Ndefo at al. 2013). In case the treatment does not work after six trials, alternative treatment methods are applied. Studies have shown that the success rate of clomiphene inducing pregnancy is 30%. The side effects of this drug include multiple pregnancies, bloating, Ovarian Hyper Stimulation Syndrome (OHSS), discomfort, hot flashes, and gastrointestinal distension (Mukherjee 2012). Antidiabetic agents can be combined with clomiphene to increase its efficiency.
On the other hand, clomiphene can be combine with metformin incase individual therapies involving the drugs fail to achieve the desired results. Gonadotropins are also used to enhance ovulation but they are only used if metformin and pioglitazone treatments fail (Mukherjee 2012). Examples of commonly used gonadotropins include Human Menopausal Gonadotropin (HMG) and Follicle-Stimulating Hormone (FSH). A gonadotropins treatment cycle involves the administration of injections on the second to fourth day of a menstrual flow. The number of injections depends on the treatment plan of each patient (Balen et al. 2005). However, many patients receive between 5 and 12 shots. During the treatment cycle, the woman is required to visit the doctor regularly for monitoring that includes blood tests, ultrasounds, and exams. In case an ultrasound reveals the presence of ripe follicles, the women is given Human Chorionic Gonadotropin (HCG) to induce ovulation (Mukherjee 2012). HCG initiates the release of the egg, secretion of progesterone, and egg maturation. Several brands of Gonadotropin have different formulations available in the market and administered through injection.
Letrozole is an aromatase inhibitor drug that regulates ovulation and enhances the chances of women becoming pregnant (Ndefo at al. 2013). The recommended dosage for this drug is 2.5 mg per day. The drug does not have positive reviews because it has been categorized by the FDA in pregnancy category D. In animals, the drug is toxic to the embryo hence the low categorization. However, a study was conducted to validate its effectiveness. The study involved 750 anovulatory women suffering from PCOS (Homburg 2001). They underwent treatment of up to five cycles. The results of the study found out that the birth rates for Letrozole were 27.5% while those for clomiphene were 19.1%. This showed that letrozole is a more effective agent than clomiphene with regard to treatment of infertility in women with PCOS. Medications that have been used to improve ovulation and fertility include insulin-sensitizing agents such as metformin, pioglitazone and rosiglitazone (Homburg 2001). A research study showed that pioglitazone is more effective than metformin in lowering insulin levels while metformin is more effective than pioglitazone in lowering body weight. In 2003, a study conducted by Cochrane suggested that metformin to be used as a first-line agent in the treatment with manifestations of infertility (Mukherjee 2012). A recent study validated the suggestion and showed the effectiveness of the drug. The results of the study revealed that six months of metformin therapy was more effective than clomiphene therapy administered for the same period (Homburg 2001).
The therapy was administered to enhance fertility in nonobese and anovulatory women with the disorder. Lack of ovulation is the main cause of infertility in women suffering from PCOS and the problem can be addressed through the administration of drugs that enhance ovulation (Ndefo at al. 2013). Before these drugs are used, a woman should be fully examined to ensure that the infertility is because of PCOS and not out of other problems. In that regard, treatment options for women with PCOS who want to get pregnant include clomiphene, metformin, and Gonadotropin (Mukherjee 2012). Clomiphene is recommended as the first-line treatment agent. If it fails, then it can be combined with metformin for better results. Gonadotropins are used sparingly because it is more expensive that the other drugs and increases the risk of multiple births.
Insulin resistance
The main symptom of insulin resistance in women with PCOS is the impairment of glucose tolerance. Insulin resistance is dangerous because it can lead to diabetes and increased risks of cardiovascular disease (Radosh 2009). Therefore, it is important to for women with the disorder to practice lifestyle modifications in addition to taking prescribed medications. A drug that improves insulin resistance is metformin and it is highly recommended as a first-line treatment for women who are not obese. Its effectiveness is evident from its classification by FDA in pregnancy category B. Other agents including pioglitazone and rosiglitazone are also used to improve insulin resistance (Homburg 2001). However, they are not commonly used because they expose women under treatment to risks of congestive heart failure and unwanted weight gain. In addition to medication, women with excessive weight should consider developing a weight loss-training program. Drugs that have been shown to be effective for weight loss include acarbose, metformin, orlistat, and sibutramine (Homburg 2001). The most highly recommended first-line agent for obesity and weight loss in metformin.
Menstrual irregularities
The most common drugs used to treat menstrual irregularities in women with PCOS are oral contraceptives. Several research studies have found out that several drugs that improve menstrual irregularities exist. Examples include spironolactone, acarbose, metformin, and rosiglitazone (Lucidi n.d.). Among these drugs, metformin is the most highly recommended because in addition to improving menstrual irregularities, it improves insulin resistance. Many doctors prescribe both control pills that comprise a combination of estrogen and progestin (Ndefo at al. 2013). Birth control pills regulate the production of androgen and allow the body to function without the continuous secretion of estrogen. This lowers the risk of contracting endometrial cancer and stops abnormal bleeding.
Some physicians advise women with PCOS to use vaginal rings or skin patches instead of birth control pills (Homburg 2001). They contain a combination of estrogen and progestin that serve the same function. Some women are allergic to combination birth control pills. Therefore, they are placed under a progesterone therapy program that is carried out after two months for 10-14 days. This therapy regulates periods and protects women against endometrial cancer. However, it does not affect the levels of androgens in the body (Lucidi n.d.). For women who do not want to get pregnant during treatment, pills that contain progestin only or intrauterine devices that contain progestin are efficacious alternatives to progestin therapy. Metformin prescription is aimed at improving insulin resistance, lowering the levels of insulin the body, enhancing ovulation, and addressing irregular menstrual cycles.
Conclusion
Over the last couple of decades, there has been a growing concern on the effectiveness of global health care delivery systems owing to the speedy rate of prevalence shown by health conditions such as Polycystic Ovary Syndrome (PCOS). PCOS refers to a chronic endocrine system disorder that affects the normal functioning of ovaries. Studies have established that it mainly affects women who have attained the age of child bearing. Some of the clinical manifestations of PCOS include high levels of androgens, missed or irregular periods, and presence of numerous small cysts in the ovaries. Before diagnosis, health care experts advise women to be very observant in noticing certain changes that give an indication of one suffering from the chronic syndrome. Some of the notable symptoms of PCOS include acne, depression, irregular periods, infertility, cysts, pelvic pain, male-pattern baldness, skin tags, and sleep apnea. Health care experts advise women to be observant as soon as possible because these symptoms can show as early as during late teenage. Other than affecting the ability of women to bear children, PCOS also increases the vulnerability of women to chronic health conditions such as diabetes and obesity. Although there is no specific treatment available for this syndrome, health care experts argue that the condition is manageable by eliminating the symptoms. Management of PCOS entails giving patients’ medications that regulate their menstrual cycle, enhance ovulation, and reduce excessive hair growth. In addition, healthy living choices such as eating a balanced diet and regular exercise apply as some of the most effective management strategies for PCOS patients because they afford a patient more freedom and responsibility in managing the symptoms.
References
Balen, A, Conway, G, Homburg, R, & Legro, R 2005, Polycystic Ovary Syndrome: A Guide to Clinical Management, CRC Press, New York.
Homburg, R 2001, Polycystic Ovary Syndrome, CRC Press, New York.
Lucidi, R n.d., Polycystic Ovarian Syndrome Treatment & Management.
Mukherjee, G. G 2012, Polycystic Ovary Syndrome, Elsevier Health Sciences, New York.
Ndefo, U, Eaton, A., & Green, M 2013, “Polycystic Ovary Syndrome: A Review of Treatment Options With a Focus on Pharmacological Approaches”, Pharmacy & Therapeutics, vol. 38, no. 6, pp. 336-355.
Radosh, L 2009, “Drug Treatments for Polycystic Ovary Syndrome”, American Family Physician, vol. 179, no. 8, pp. 671-676.