Pill-Induced PCOS - A Myth or Reality

Introduction:

Oral contraceptives are one of the most commonly used medicines. Around 25 percent of women between the age of 15 to 44 consume oral contraceptives. These drugs can also be used for other medical purposes. But these drugs have several side effects also. The development of polycystic ovarian syndrome-like symptoms is also associated with using oral contraceptives.

What Is PCOS?

PCOS, or polycystic ovarian syndrome, is a condition characterized by the increased level of male hormones in the body. In this condition, multiple fluid-filled sacks in the ovary can be detected. Almost four to twenty percent of women worldwide are suffering from this hormonal disorder.

What Are the Causative Factors?

The cause of this condition is unknown. But several risk factors have been identified which may cause this disorder. These are:

1. Familial and Genetic Factors: Familial factor is one of the most distinctive features of PCOS. Different genes associated with steroidogenesis are responsible for this condition. Malfunctioning associated with CYP11a, CYP21, CYP17, and CYP19 genes is related to PCOS.

2. Lifestyle Factors: PCOS is very much related to lifestyle. Obesity is one of the key factors which is responsible for PCOS. Obesity is responsible for altering metabolic functions, which causes PCOS. Smoking, drinking, and unhealthy food habit are associated with PCOS.

These two factors are responsible for defects in the hypothalamic–pituitary–ovarian (HPO) axis. Due to the effect of these factors, the level of androgen (male sex hormone) remains high. The high level of androgen causes an elevation in the level of luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH). The level of follicular-stimulating hormone (FSH) remains unchanged or slightly decreases. This causes alliteration in the ratio between luteinizing hormone (LH) and follicular-stimulating hormone (FSH). As a result, ovulatory events may decrease, and the amount of circulating progesterone decreases. Insulin resistance is a crucial factor for hormonal imbalance. In insulin resistance, the amount of sugar the in the blood is high; also, the production of insulin is increased. This is associated with the abnormal functioning of serine/threonine kinase (an enzyme that regulates cell functioning) enzyme. These enzymes are also associated with androgen biosynthesis. Also, increased insulin level lowers the level of sex hormone binding globulin, which disrupts the body's androgen level regulatory mechanism. Excessive insulin also decreases the level of DHEAS (dehydroepiandrosterone sulfate, a type of steroid), which regulates the amount of estrogen and androgen in the female body. Obesity and chronic inflammation also play crucial roles in PCOS, as all these factors disrupt the function of neurotransmitters and the hypothalamic-pituitary-adrenal (HPA) axis.

What Are Oral Contraceptives?

Oral contraceptives are hormonal pills will are used but birth control. Based on hormonal components, oral contraceptives can be divided into two types, these are:

1. Combined oral contraceptive (COC).

2. Progesterone-only pill (POP).

Combined Oral Contraceptive (COC) - A combination of two hormones is found in this pill. These are estrogen and progesterone. While the estrogen component remains the same for these drugs, the progesterone component may vary in different drugs, and this component is known as progestin. Different generations of progesterone can be used:

• First-Generation Progestin: These are the least potent, and the molecules are: Norethindrone acetate, Ethynodiol diacetate, Lynestrenol, and Norethynodrel.

• Second Generation Progestin: Levonorgestrel and dl-Norgestrel are the molecules belonging to this generation.

• Third Generation Progestin: These molecules are Norgestimate, Gestodene, and Desogestrel.

The first two generations of progesterones are derived from testosterone derivatives; as a result, they have androgen receptor (male receptor hormone) affinities. Also, they may cause androgenic side effects (side effects due to male hormones). But the third-generation progesterones have negligible side effects on adrenergic receptors. Recently, several new forms of progestin like Trimegestone, Nestorone, Nomegestrol, Cyproterone Acetate (CPA), and Chlormadinone acetate have developed to reduce the androgenic side effects, and all these are derived from progesterone.

Progesterone-only Pill (POP) - These are mini-pills used in cases where patients are intolerant to combined oral contraceptives. These are either derived from Drospirenone or Norethindrone. These pills are taken in low daily doses of progestins (e.g., Levonorgestrel 30 micro-grams, Norethindrone 35 micro-grams, Desogestrel 75 micro-grams) and need to be used continuously, except for the Drospirenone-only pill, which is taken daily for 24 days followed by four days of placebo.

What Is the Mechanism of Contraception?

The combined oral contraceptives are administered for a 21-day cycle followed by a 7-day pill-free cycle to mimic a 28-day menstrual cycle. Progesterone on the pill acts on the hypothalamus to decrease the pulse frequency of the gonadotropin-releasing hormone. This causes a reduction in the secretion of follicle-stimulating hormone (FSH) and decreases the secretion of luteinizing hormone (LH). This also alters the level of estrogen in the body. As a result, the follicles are unable the develop, and the release of the egg is prevented.

The mechanism of action of the progesterone-only pill is different. The amount of progesterone in such pills is less to prevent ovulation. But these pills change the molecular structure of the mucus and increase its viscosity and cell content. This prevents the sperm from penetrating and prevents fertilization.

What Is the Role of Contraceptives in PCOS?

The most commonly used medication for PCOS is combined oral contraceptives. The hormonal component present in these drugs maintains the hormonal balance in the following ways:

• The progestin component of contraceptives inhibits ovarian androgen production by suppressing luteinizing hormone (LH) production.

• Progestin prevents the androgen from binding to its receptors.

• The estradiol component of the contraceptive increases the level of sex hormone-binding globulins and reduces the concentration of s serum-free androgens.

• It also decreases adrenal androgen production.

What Are the Complications?

As oral contraceptives are increasing daily, many patients are suffering from different types of complications related to the use of such medications. These are:

1. Breakthrough bleeding: Bleeding in between periods is the most common side effect.

2. Nasua, vomiting, and headache are commonly observed.

3. The incidence of venous thromboembolism (blood clot in the vein) is a serious side effect of oral contraceptives. Women over 35, smoking, or drinking age are the key risk factors associated with developing venous thromboembolism after taking oral contraceptives for prolonged periods.

4. Chronic use of contraceptives increases the risk of myocardial infarction and stroke (less oxygen supply to the heart and brain). That is why it is contraindicated in PCOS patients with cardiac disorders.

5. Pill-induced PCOS: This is a misnomer and is often called temporary PCOS. This is not true PCOS. After the stoppage of the pills, withdrawal symptoms developed due to the serge of the androgen. As a result, irregular periods or absence of periods may be observed. This is mainly associated with pills containing drospirenone or cyproterone. These conditions are self-limiting and usually automatically disappear after three to four months.

Conclusion:

PCOS is caused by hormonal imbalance. Oral contraceptives can be used in PCOS to treat such imbalances. Proper medical history should be taken before prescribing these drugs, as serious complications like strokes may happen. Pill-induced PCOS is a temporary condition caused by the withdrawal of contraceptive pills. This should not be confused with PCOS. Moreover, oral contraceptives are safe drugs and can be used in various conditions.