Polycystic Ovary Syndrome and its Most Common Drug List

Polycystic ovary syndrome (PCOS) is a metabolic disorder occurring due to hormonal imbalance and affecting women in their reproductive age. It is a condition affecting the proper functioning of ovaries. A woman is required to have at least two of the three below mentioned symptoms for having PCOS:

• Irregular menstrual periods, indicating intermittent ovulation
• Elevated levels of androgens or male hormones
• Polycystic ovaries, in which the ovaries have small sac shaped fluid filled structures called cysts, causing hormonal imbalance.

Contrary to popular belief, having PCOS does not mean that you will have cysts in your ovary. The name might be misleading as polycystic ovary (PCO), polycystic ovary disorder (PCOD) and polycystic ovary syndrome (PCOS) are all different conditions. PCO is not a disease but an alternate form of normal ovaries. A number of factors can cause multiple cysts to develop in the ovary. These women do not have any problem in conception and the condition is only discovered by chance. PCOD is a condition arising solely due to hormonal imbalance. Cysts are immature follicles which are found in the ovary. PCOS is a metabolic condition in which polycystic ovaries might or might not be present. Pituitary and thyroid dysfunction are first ascertained before diagnosing a woman with PCOS. Patients of PCOS also have high levels of insulin in their blood.

PCOS affects about 5-10% women in child bearing age, causing the U.S. government to spend nearly 4 billion USD on correctly diagnosing and managing PCOS.

Symptoms of PCOS

Some of the commonly observed symptoms of PCOS are:

• ‘String of pearl’ cysts on the ovaries
• Irregular menses
• Infertility
• Insulin resistance
• Excessive hair growth on face and body (hirsutism)
• Acne
• Male pattern baldness
• Dark, thick patches of skin on the neck, arms, breasts or thighs
• Skin tags in the armpits or neck area
• Pelvic pain
• Anxiety and Depression
• Sleep apnea

Treatment of PCOS

Currently, there is no cure for PCOS. However, its symptoms can be effectively managed by making certain lifestyle changes like weight reduction, being physically active and following a healthy and balanced diet. It can also be managed through different medicines. Treatments of PCOS can be done according to the symptoms the patient is experiencing and includes the following

I. Regulating menstrual cycle

a. Birth Control Pills
Birth control pills or oral contraceptives contain synthetic derivatives of two female hormones, estrogen and progesterone. These pills help in inducing regular predictable, cyclic periods.

1. Progesterin: These are drugs which are the chemical derivative of female hormone, progesterone. They perform the following functions:

• Suppression of luteinizing hormone
• Inhibition of luteinizing hormone surge
• Reduction in secretion of ovarian androgen
• Possession of androgen blocking effects

Some of the drugs belonging to this class are:

• drospirenone
• norgestimate
• norethindrone
• norgesterol
• levonorgesterol
• desogestrel

2. Estrogen: Ethinyl estradiol is the chemical derivative of the naturally occurring female hormone, estrogen. It is added in the OCPs for the following effects:

• Suppression of follicle stimulating hormone (FSH)
• Stabilization of endometrium
• Potentiation of progestin action
• Suppression of dominant follicle formation
• Escalation in sex hormone binding globulin
• Reduction in free androgen

These drugs are generally given in the form of birth control or contraceptive pills and are given as combination of progestins and synthetic estrogen.

Drug Combination: ethinyl estradiol and levonorgestrel
Brand: Alesse
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and levonorgestrel
Brand: Aviane
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and levonorgestrel
Brand: Enpresse
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and norethindrone acetate
Brand: Estrostep Fe
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and levonorgestrel
Brand: Lessina-28
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and norethindrone acetate
Brand: Lo Loestrin Fe
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and norethindrone acetate
Brand: Loestrin Fe 1/20
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Side Effects of OCPs: Intermenstrual bleeding, nausea, headache, weight gain, mood changes, decreased libido, abnormal vaginal discharge and breast tenderness

II. Fertility Problem

a. Ovulatory stimulants: These are the drugs that stimulate the ovaries to release eggs or ovum. These drugs are structurally similar to estrogen and bind to estrogen receptors, tricking the brain to believe that estrogen levels are low in the body so the brain is unable to provide accurate negative feedback to hypothalamus. Therefore, gonadotropin releasing hormone is released, which stimulates pituitary gland to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). These hormones enhance the growth and development of ovarian follicles and promote ova release.

Drug: clomiphene
Brand Names: Clomid
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Nausea, diarrhea, flushing, abnormal vaginal/uterine bleeding and breast tenderness

b. Aromatase Inhibitor: Aromatase is an enzyme which is expressed in ovarian granulosa cells, placental cells and others. Estradiol, a form of female hormone estrogen, is also secreted by the ovarian granulosa cells. This estradiol is produced from cholesterol in our body and its rate of synthesis is controlled by aromatase. These drugs inhibit the activity of aromatase enzyme and hence the amount of estradiol produced also decreases, which stimulates the pituitary gland to secrete follicle stimulating hormone (FSH), causing ovulation. It is prescribed in women who are resistant to ovulatory stimulants like clomifene.

Drug: letrozole
Brand Names: Femara
Dosage Form: Tablet
The U.S. FDA Status: Approved
Availability: Prescription only
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Bone fracture, edema, dizziness, fatigue, osteoporosis, flushing and hypercholesterolemia

c. Selective Estrogen Receptor Modulator (SERM): Although these drugs are chemically related to ovulatory stimulants, they have complex actions. It has a potent estrogen inhibitory action in breast cancer while weak estrogen stimulatory action in uterus, liver, bone and pituitary. The weak stimulatory action of estrogen on uterus causes thickening of endometrium- the inner most lining of uterus. These drugs block the action of estrogen in hypothalamus- a part of brain, which sends a strong signal to the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone, causing ovulation.

Drug: tamoxifen
Brand Name: Nolvadex
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No, unless the benefits outweigh the risks
Alcohol Content: No
Side Effects: Amenorrhea, hot flashes, nausea, vaginal discharge and hemorrhage, weight loss and skin changes

III. Increased level of insulin or Hyperinsulinemia

a. Biguanides: Pancreas produces insulin, which facilitates the uptake of glucose by the cells to produce energy. In PCOS patients there is a chance of insulin resistance where cells do not respond properly to insulin. This increased amount of insulin in the body can cause the ovaries to produce more amounts of male hormone, testosterone.

In order to decrease your blood glucose levels, biguanides are prescribed. By lowering your blood glucose levels, your body decreases the synthesis of insulin and hence testosterone. Although the U.S. FDA has not approved use of biguanides in PCOS, it is still prescribed.

Side Effects: Nausea, diarrhea, loss of appetite and flatulence.
Drug: Metformin
Brand Names: Glucophage, Fortamet, Riomet
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: Yes, only during first trimester
Alcohol Content: No
Side Effects: Lactic acidosis, nausea, diarrhea, flatulence and deficiency of vitamin B12

IV. Hair loss and Hirsutism:

Women having PCOS tend to develop male pattern baldness and excessive facial and body hair due to increased testosterone levels in the body. A healthy lifestyle, frequent exercise, nutritional supplement and a good diet along with medicines are useful in treating PCOS symptoms. Some of the drugs that are prescribed for managing hair loss and hirsutism symptoms are:

a. Oral contraceptive pills (OCP): Hormonal contraception provided by the oral contraceptive pill (OCP) decreases the production of testosterone and other androgens from ovaries along with sex binding globulin (SHBG), which is a protein synthesized by your liver, adhering tightly with sex hormones like estrogen, testosterone and dihydrotestosterone found in both men and women. The amount of SHBG is very low in women with PCOS and therefore, the level of free testosterone in the blood increases and causes excess facial and body hair, and male pattern baldness. Through the pill, SHBG production is increased which binds the extra testosterone and helps in reducing the symptoms produced by excessive androgen.

Side Effects: Intermenstrual bleeding, nausea, headache, weight gain, mood changes, decreased libido, abnormal vaginal discharge and breast tenderness

Drugs: Following drugs are generally present in combination in OCPs:

• cyproterone acetate
• ethinyl estradiol
• desoestrol
• drospireone
• norgestimate

Drug Combination: desogestrel and ethinyl estradiol
Brand: Desogen
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: desogestrel and ethinyl estradiol
Brand: Ortho-Cept
The U.S. FDA Status: Discontinued
Dosage Form: Oral
Indicated in Pregnancy: No
Alcohol Content: No

Drug Combination: ethinyl estradiol and norgestimate
Brand: Ortho Tri-Cyclen
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No

b. Diuretic as Androgen Inhibitors: Spironolactone, a diuretic, is used for treating hair loss in women because of its additional androgen inhibiting property. Although it is not approved by the U.S. FDA for treating hair loss, it is still prescribed by the doctors. It prevents synthesis of androgens, like testosterone, and existing androgen, like dihydrotestosterone (DHT)- which is responsible for hair loss- are prevented from binding to the androgen receptors.[Source]

Drug: spironolactone
Brand Name: Aldactone
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No. Prescribed only if there is edema during pregnancy [Source]
Alcohol Content: No
Side Effects: Abdominal cramping, bleeding gums, breast pain, chest pain, chills, dizziness and headache

c. Anti-Androgens: These drugs work by blocking the action of androgens, which are responsible for causing male patterned baldness and hirsutism in women having PCOS. Androgen receptors present on the hair follicles are blocked by these drugs so that androgens cannot act on them and hence, are unable to produce the unwanted effects. By taking these drugs, you might notice you have thicker hair and less body hair.

Drug: flutamide
Brand: Eulexin
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Diarrhea, stomach pain, frequent urge to urinate, black stools, pale skin, unusual bleeding

Drug: finasteride
Brand: Proscar
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Chills, confusion, dizziness, cold sweats, itchy skin, skin rash and unusual weight gain

d. Ornithine Decarboxylase Inhibitors: These drugs decrease hair growth but do not remove them completely. Hair follicles undergo rapid growth and maturation when they transform into hair and require certain proteins, called polyamines, whose production depends on the activity of any enzyme, ornithine decarboxylase (ODC). These drugs block the activity of ODC and decrease the growth and differentiation of cells present within hair follicle.

Drug: eflornithine
Brand: Vaniqa
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Topical cream
Indicated in Pregnancy: No
Alcohol Content: No
Side Effect: Acne, stinging skin, rash, numbness and tingling skin

V. Weight Loss:

a. Lipase Inhibitors: These are the drugs that work by inhibiting the absorption of fat from the gut. The unabsorbed fat is then excreted out of body in feces. These drugs are used along with low-calorie, low-fat diet and regular exercise program in order to help people in weight reduction.

Drug: orlistat
Brand: Xenical
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Capsule
Side Effects: Bladder pain, body aches, muscle pain, nausea, diarrhea, fever, sweating and headache

VI. Cholesterol Lowering Drugs:

a. Statins: These are the drugs which help in reducing blood cholesterol level by decreasing the production of cholesterol by liver by inhibiting the action of an enzyme HMG CoA reductase.

Drug: atorvastatin
Brand: Lipitor
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Fever, weight gain, tiredness, dark colored urine, unexplained muscle pain and tenderness

Drug: lovastatin
Brand: Altoprev
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: cough, fever, headache, joint pain, lower back pain, unusual tiredness, stuffy nose and muscle ache

VII. Acne Treatment:

a. Retinoids: These drugs help in shrinking the sebaceous glands and thereby decrease production of sebum. This reduces the outbreak of acne. It should not be used by pregnant women or those who are trying to conceive.

Drug: isotretinoin
Brand: Absorica
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Capsule
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Eczema, dry skin

b. Oral Contraceptive Pills (OCP): These medicines contain hormones which can help in reducing acne and give clearer skin. However, you have to be patient with this treatment as it might take a few months to show its effect.

Drugs: norethindrone and ethinyl estradiol
Brand: Estrostep FE
US FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Nausea, headache, bloating, vomiting, breast tenderness, weight change, abnormal vaginal bleeding and hypertension.

Drugs: norgestimate and ethiny estradiol
Brand: Ortho Tri-Cyclen
US FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Abdominal pain, irregular periods, anxiety, chills, diarrhea, fainting, fever, headaches, itching and rashes

c. Anti-androgen drugs: Spironolactone, a diuretic, is also an anti-androgen drug. It is used for managing conditions like hypertension and congestive heart disease. Spironolactone helps by blocking testosterone receptors and decreases testosterone production in the body. This helps in reducing sebum production and hence acne outbreak is reduced.

Drug: spironolactone
Brand: Aldactone
US FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Abdominal pain, bloody urine, chest pain, chills, constipation, diarrhea, dizziness and headache

OTC Drug List

Some of the drugs that are available over-the-counter in some of the most traveled countries are:

Levonogestrel	Orlistat	Isotretinoin
China	China	India
Mexico	The U.S.A.
Denmark	Austria
South Korea	Greece
Australia	UK
The Netherlands	Ireland
France	Croatia
Greece	Hungary
Czech Republic	France
Spain	The Netherlands
UK	Czech Republic
Switzerland	Italy
Ireland	Singapore
Austria	Switzerland
The U.S.A.	Spain
	Germany
	Mexico
	Denmark
	Philippines
	Australia