Pleiotropic effects occur when a drug influences biological pathways outside of its intended target.
The term “pleiotropy” comes from the Greek words pleio (many) and tropos (ways), meaning that a single medication can produce a variety of effects across different systems in the body, extending beyond its primary purpose.
Medications can be powerful tools, but they are rarely without ripple effects on the body. No system works in isolation, so manipulating certain pathways or substances in the body can have unintended consequences. Understanding these broader impacts is key to making balanced treatment decisions that maximize benefits and minimize harm.
Aspirin
Intended effects: Reduces pain, inflammation, and fever (analgesic and anti-inflammatory). Inhibits blood clotting by blocking platelet aggregation (antiplatelet effect).
- Inhibits the aromatase limiting the conversion of testosterone to estrogen
- Lowers free fatty acids (FFAs) and improves glucose metabolism
- Reduces risk of preeclampsia and miscarriage
- May reduce the risk of certain cancers (colorectal, breast, lung, etc.)
- Increases progesterone
- Protects against cardiovascular events like heart attacks and strokes
Statins
Intended effects: Lowers cholesterol by inhibiting HMG-CoA reductase.
- Impair glucose metabolism, increasing risk of type 2 diabetes
- Reduce production of coenzyme Q10, affecting mitochondrial energy production
- Inhibit the synthesis of vitamin K, increasing calcification of soft tissues
- Reduce inflammation (lower C-reactive protein levels)
- Cause muscle pain or weakness (myopathy)
- High doses decrease angiogenesis (the formation of new blood vessels)
- Impair glucose metabolism, increasing risk of type 2 diabetes
SSRIs:
Intended effects: Treats depression & anxiety by increasing serotonin availability.
- Impair glucose metabolism, increasing risk of type 2 diabetes
- Increase intestinal inflammation and the risk of developing irritable bowel syndrome (IBS)
- May cause sexual dysfunction, including reduced libido
- May reduce leptin sensitivity and increase ghrelin, leading to weight gain
- Decrease dopamine levels
- Have potential cardiovascular benefits by reducing platelet aggregation
ACE Inhibitors
- Reduce proteinuria, protecting kidney function
- Reduce the production of reactive oxygen species (ROS), protecting cells from oxidative damage
- Increase bradykinin levels, causing a persistent dry cough
- Increase nitric oxide, impairing oxygen use in cells
- Can reduce brain inflammation by improving blood flow
- May lead to hyperkalemia (high potassium levels), affecting heart and muscle function
Corticosteroids
Intended effects: Reduces inflammation and suppresses immune responses by mimicking cortisol.
- Break down bone tissue, increasing risk of osteoporosis and bone fractures
- Decrease prostaglandins
- Lower antibodies associated with autoimmunity
- Increases blood pressure by increasing fluid retention
- Can cause hyperglycemia, increasing the risk of diabetes
- Suppress the immune system, raising the risk of infections
Metformin
Intended effects: Improves insulin sensitivity and lowers blood sugar levels.
- Activates AMPK, regulating ATP & energy production
- Can lower TSH in hypothyroidism
- Reduces inflammation by lowering cytokines & inhibits NF-κB
- Depletes vitamin B12 with long-term use, leading to anemia or nerve damage
- Can cause lactic acid buildup
- Promotes mitochondrial fatty acid oxidation
Combined Hormonal Contraceptives (Estrogen & Progestin pills)
Intended effects: (Estrogen / progestin pill) Prevents ovulation and alters cervical mucus to reduce the likelihood of pregnancy.
- Can reduce acne by reducing androgen levels
- Reduce irregular periods by masking underlying imbalances
- Increase risk of breast and cervical cancer by suppressing natural progesterone production
- Deplete levels of B vitamins (B2, B6, B12, and folate, vitamin C, vitamin E, magnesium, selenium, and zinc
- Increase C-reactive protein (CRP) and systemic inflammation
- Estrogen releases clotting factors, raising risk of blood clotting
Polypharmacy—the use of multiple medications—is increasingly common in healthcare and often driven by the negative pleiotropic effects of drugs. Prescribing one medication frequently leads to the need for additional drugs to manage side effects or unintended outcomes.
For example, hormonal birth control is often prescribed to regulate menstrual cycles or for contraception but has been linked to mood changes and depression. Hormonal contraceptives alter neurotransmitter levels like dopamine, reduce natural progesterone, and increase inflammation or cortisol, all of which can contribute to depressive symptoms. A large Danish study found that women using hormonal contraceptives were 80-120% more likely to start using antidepressants compared to non-users, with the risk being highest among adolescent girls (Skovlund et al., 2016).
Relying on these drugs long term and continuing to prescribe additional medications to manage their side effects prevents us from understanding what is happening in the body. Many of them act as a band-aid, masking underlying imbalances. These medications can be helpful, but should be used with care. A doctor’s goal should be to get you off of drugs that have serious pleiotropic side effects as soon as possible.
It’s important to research and understand what you’re taking, especially since doctors don’t always disclose all the potential effects of medications—often because the full extent of a drug’s impacts isn’t fully understood or communicated. Mytavin (mytavin.com) is a helpful resource that outlines nutrient depletions caused by common medications.
Medicine is often seen as a science, but at its core, it is also an art—one that requires a deep understanding of nuance. While the complexity of pleiotropic effects presents opportunities—like the added anti-inflammatory benefits of aspirin—it also calls for caution. A medication prescribed for one issue can sometimes lead to new challenges. Healing is rarely a straightforward process.
There are rarely any magic bullets, and with more than half of Americans (51.8%) on at least one medication to manage a long-term condition, it’s important we understand what we are taking. Thoughtful medical care acknowledges the complexity of pleiotropic effects and prioritizes an approach that addresses the whole person.