Yaz® and Yasmin® are birth control pills (oral contraceptives) made of ethinyl estradiol (an estrogen) and the progestin drospirenone. Yaz, which contains a lower dose of estrogen than Yasmin, is the best-selling oral contraceptive in the US. But since the FDA approved Yasmin in 2001, and Yaz in 2006, it has become clear that drospirenone can have uniquely dangerous side effects.

Goes Beyond Birth Control to Side Effects

Bayer, the manufacturer of Yaz, has marketed it as the “third generation” birth control pill that “goes beyond birth control.” The third generation label is meant to imply that the drospirenone in Yaz is an advance in oral contraceptives, but the truth is that this synthetic progesterone (progestin) is keeping Bayer in court with lawsuits over side effects.

The “goes beyond birth control” marketing refers to the two conditions that the FDA has approved Yaz for, which is to treat “moderate” acne and premenstrual dysphoric disorder (PMDD), which is severe PMS. Yaz has not been approved for treatment of regular PMS. Yaz was promoted so aggressively as an anti-acne and anti-PMS pill, that in 2009 the FDA cited Bayer for misleading advertising that underplayed the potentially serious side effects of Yaz, and required that it run ads correcting the misperception that it is a lifestyle drug rather than a birth control pill.

It's Not More Like Progesterone

Early on, drospirenone was marketed to doctors as being closer to progesterone than most of the progestins found in oral contraceptives, but the truth is that it’s far from similar to progesterone in its effects, and in fact closely resembles the drug spironolactone, used as a diuretic and anti-androgen. A diuretic stimulates the body to release water and thus can reduce bloating, but it can also cause dehydration, low blood pressure, heart palpitations and more. Androgens are male hormones, which play a pivotal role in a healthy libido.

According to Bayer’s Physician Information, “Yaz contains 3 mg of the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to a 25 mg dose of spironolactone.” This means that drospirenone can increase potassium to dangerous levels, which is called hyperkalemia.

Potassium is a mineral and ion, one of the body’s electrolytes, which maintain fluid balance in the cells. Other electrolytes include sodium (salt), calcium and magnesium. Potassium is closely tied to muscle, brain and digestive functions.

Your doctor may or may not be aware of the possible side effects associated with drospirenone. As Ob/Gyn Dr. Jennifer Landa points out, “I was mildly warned by the drug rep who came to my office to introduce Yaz, and was just told not to prescribe it in women with kidney disease. There are many more circumstances in which a woman can run the risk of hyperkalemia and a doctor may unknowingly add to the mix by not being educated fully on the risks that women may incur in taking this form of progestin.  Many doctors are not even fully aware of the risks of progestins in general and how they differ very much from progesterone.  There are some very important differences to be aware of with progestins in general and drospirenone in particular.

“Side effects are very common with progestins that are not seen with progesterone.  These can include increased appetite, weight gain, fluid retention, irritability, depression, headaches, decreased energy, acne, decreased sexual interest and so much more. Even more serious, progestins have been associated with an increased risk of breast cancer and clots.  I now avoid prescribing progestins to my patients and tend to favor non-hormonal contraceptive methods such as the paraguard IUD or barrier methods as appropriate.”

Symptoms of Hyperkalemia (high potassium)

Symptoms of hyperkalemia include fatigue, muscle weakness, heart palpitations and rapid breathing, and if potassium gets high enough it can cause heart rhythm disturbances, which can disrupt blood flow enough to cause stroke, heart attack, kidney failure and clots in the lungs. Yaz has also been reported to cause gallbladder disease.

According to the prescribing information for spironolactone regarding hyperkalemia, warning signs of electrolyte imbalance can include “…dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension [low blood pressure], oliguria [decreased production of urine], tachycardia [irregular heart rate], and gastrointestinal disturbances such as nausea and vomiting.”

In spite of all these possible warning signs, hyperkalemia often comes on suddenly, with no warning signs, and can be fatal.

What Raises Potassium Levels

Although hyperkalemia is relatively rare among Yaz users, when millions of women are using it, even a rare side effect can cause problems in hundreds, if not thousands of women.

There are many ways that potassium can become elevated, which all users of Yaz should be aware of.

The kidneys are responsible for removing excess potassium from the body, so first and foremost, those with kidney disease need to be aware of hyperkalemia, and in fact should not even take Yaz.

Aldosterone is the hormone, made by the adrenal glands, that helps the kidneys regulate potassium levels. It is affected most by Addison’s disease, which causes low adrenal hormones. Addison’s is the extreme form of low adrenal hormones, but “tired” adrenals or adrenal insufficiency is virtually epidemic among 40-something women who are chronically stressed because they are trying to manage motherhood and jobs. Tired adrenals lead to low aldosterone levels, which leads to poor regulations of potassium levels.

Since 98% of potassium is stored in the cells, anything that moves potassium out of cells and into the bloodstream can cause or contribute to hyperkalemia. One good example is insulin resistance, which is common in people who are obese.

Liver disease, diabetes, and heart disease can also make hyperkalemia more likely and more risky.

Taking high doses of the amino acids lysine and arginine can cause potassium to move out of cells and into the bloodstream.

Excess ingestion of fluoride, which applies to most people drinking fluoridated water, and/or using fluoridated toothpaste and mouthwash, can inhibit the manufacture of aldosterone in the adrenal glands, which can increase potassium levels.

Salt substitutes (AlsoSalt, NoSalt) substitute potassium chloride for salt.

Many blood pressure drugs increase the risk of hyperkalemia, include the ACE inhibitors, angiotensin-II receptor agonists, beta-blockers, potassium-sparing diuretics and of course, spironolactone. Heparin and digitalis can also increase potassium levels.

The non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and naproxen (Aleve) are associated with elevated potassium levels.

While none of the above factors, aside from diabetes, and kidney and heart disease and their attendant drugs, are likely to raise potassium to dangerous levels, it’s not hard to imagine a scenario where a combination of events could lead to hyperkalemia. For example, let’s say that an overweight, chronically stressed 40-something woman taking Yaz, is taking ibuprofen for headaches, lysine for herpes, washes the pills down with noni juice (high in potassium), eats a banana (high in potassium) and then gargles with a fluoridated mouthwash. She has high blood pressure so her doctor has told her to cut down on salt, so she’s using AlsoSalt. Is this a recipe for a stroke or heart attack? Maybe.

Be Aware

Some women may prefer Yaz because it doesn’t have androgenic (male hormone) effects, but it’s important to be aware that it does carry the usual risks of oral contraceptives and an extra risk of hyperkalemia that could lead to any number of side effects, as minor as occasional muscle weakness and as major as a stroke or heart attack.

The take-home message here is that women who take Yaz should be well-educated and aware of its risks and side effects.

References

Hollander JC, Calvert FJ, Hyperkalemia, Am Fam Physician, 2006 Jan 15;73(2):283-290, http://www.aafp.org/afp/2006/0115/p283.html#afp20060115p283-t1.

Kemmeren JM, Algra A, Grobbee DE, “Third generation oral contraceptives and risk of venous thromboembolism: meta-analysis. BMJ,” 2001;323:1–9.

Pearce HM, Layton D, Lynda V et al, “Deep vein thrombosis and pulmonary embolism reported in the Prescription Event Monitoring Study of Yasmin,” Br J Clin Pharmacol. 2005 July; 60(1): 98–102.

Van Grootheest K, Vrieling T, “Thromboembolism associated with the new contraceptive Yasmin. BMJ,” 2003;326:257.

van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP et al, “The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study,” BMJ 2009 339: b2921.