Introduction:
Tramadol is an opioid medication. Doctors may prescribe Tramadol medications to treat moderate to moderately severe pain. When Tramadol enters a person’s body, the liver changes it to its active form which is O-desmethyl Tramadol also known as M1. Both M1 and Tramadol can relieve pain and may also cause side effects in some people. M1 has stronger opioid effects compared to Tramadol. However, only a few studies exist exploring the risk of an adverse effect of this drug on fertility, pregnancy, and breastfeeding women. Studies have consistently found that prescription opioids are the most commonly prescribed drugs and the prevalence of its use is increasing among women.
What Is the Mechanism of Action of Tramadol?
Tramadol's mechanism of action implicates multiple pathways, including following:
- Mu-opioid receptor agonism that inhibits pain signals.
- Inhibits norepinephrine and serotonin reuptake for raised availability of these neurotransmitters.
- Activation of descending inhibitory pathways.
- N-methyl-D-aspartate (NMDA) receptor antagonism.
- Metabolism to an active metabolite, O-desmethyl-tramadol.
These actions collectively deliver analgesic effects. Tramadol may also impact other neurotransmitter systems such as glutamate, gamma-aminobutyric acid (GABA), and adenosine. Its unique dual mechanism, involving both opioid and non-opioid pathways, sets it apart from traditional opioids.
What Are the Effects of Taking Tramadol During Pregnancy?
Many studies have established that opiates or opioids during pregnancy have harmful effects on the fetus or child of a mother taking the drug during pregnancy, especially during the late stage of pregnancy neonatal abstinence symptoms are common. Tramadol administration during pregnancy results in profound structural abnormalities on the cerebellar cortex (a part of the brain) of the fetus and can be associated with oxidative stress indicated by raised lipid peroxidation products and the lowering of antioxidant enzyme activities. These effects result in neonatal abstinence syndrome in newborns.
What Impact Does Tramadol Have on the Fetus When Taken During Pregnancy?
Very little is known about the effects of prescribed opioids as painkillers during early pregnancy on the fetus. Some studies suggest a weak teratogenic effect (possibility of congenital disorders in a growing embryo or fetus) of Tramadol, specifically regarding cardiovascular defects and congenital talipes equinovarus also known as club-foot. Club foot is a common developmental disorder of the legs of a newborn, despite the appearance of deformity of the lower limb, the baby does not have any other abnormalities in the club foot. However, If exposure to Tramadol has occurred during early pregnancy, the actual risk is small, and also the malformations if occurred are not very serious. However, taking Tramadol during the late stage of pregnancy commonly causes neonatal abstinence syndrome.
Neonatal Abstinence Syndrome: It is a spectrum of clinical manifestations in neonates caused by withdrawal from intrauterine drug exposure. A baby with this syndrome may have clinical symptoms such as the followings;
- Body tremors.
- Seizures.
- Overactive reflexes.
- Tight muscle tone.
- Fussiness, excessive high-pitched crying.
- Poor feeding, sucking, and slow weight gain.
- Breathing problems including fast-paced breathing.
- Fever and sweating.
- Blotchiness of the skin.
- Trouble sleeping with lots of yawning.
- Diarrhea.
- Vomiting.
What Are the Effects of Tramadol While Breastfeeding?
Almost all drugs including Tramadol, get transferred into the breast milk to a certain extent. Drugs can enter the breast milk through passive diffusion, but carrier-mediated transport or some active transport are also present. Breast milk has a pH little lower than blood plasma. Thus, due to its higher acidity, ion trapping can occur in breast milk for drug particles with weak bases. In addition, infant exposure to drugs due to breastfeeding is dependent on the ratio of milk to plasma, infant drug clearance, and breast milk intake.
Effect of Tramadol on Baby - A small clinical trial noted infants were exposed to less than three percent of a mother’s dose of Tramadol through breast milk with no indication of harmful effects and instructed short-term use by the mother of Tramadol was compatible with breastfeeding. However, the literature is quite contradictive regarding the safety of Tramadol for use in breastfeeding mothers. A case study strongly instructs against Tramadol in breastfeeding mothers due to the death of a baby exposed to Tramadol via breast milk of a Tramadol-addicted mother.
Hence, the Food and Drug Administration (FDA) of The United States does not recommend breastfeeding during treatment with Tramadol due to the risk of serious adverse reactions in breastfed babies such as excessive sleepiness, difficulty in breastfeeding, and serious breathing difficulties, which may lead to the death of the infant.
Does Tramadol Intake Impact the Fertility of Women?
Current data regarding the impact of Tramadol use on women's fertility are very scarce and nonconclusive. On the other hand, the mechanism of the chronic pain with depression relationship may induce changes with respect to endocrine (hormonal), immune, and mechanical factors. These may reduce women's fertility, whereas psychological factors including depression, anxiety, and stress can also negatively impact the fertility of women.
Severe pain affects the endocrine system by the stimulation of the hypothalamic–pituitary–adrenal axis system, which in turn leads to elevated levels of adrenocorticotropic hormone, cortisol, and pregnenolone levels. In cases where pain persists for too long, it can harm the hormonal system, and hormone production may decline which leads to serum hormone levels decreasing below normal. For female reproductive system regularization, hormonal balance is critical. Hence, any irregularities in hormonal balance may negatively hamper a woman's fertility as well as sexual functions.
There is no clear evidence currently that suggests the impact of Tramadol on women’s fertility. However, a few studies have reported that Tramadol may affect the menstrual cycle of women. On the contrary, not taking painkillers despite the pain, or having non-effective painkillers may chronically increase the stress level in women, which can negatively impact women’s fertility.
In a study of a female animal model, the use of Tramadol led to a decrease in the number of ovarian follicles with ovarian dysfunction. This study suggests that Tramadol inhibits female reproductive system functions and hormones. Tramadol was found to significantly lower the fertility of female animal subjects.
Conclusion:
Due to its popularity and wide use especially among the younger population as a pain killer Tramadol dependence has become a problem. Women should take safe and effective medications during pregnancy and while breastfeeding. Careful consideration is paramount for both the pregnant woman’s medical concerns and the potential harm to the fetus inside the womb. Even in the case of breastfeeding women, potential adverse effects on the baby may occur. In situations where the use of Tramadol can be avoided, it is better to consider the usage of other alternative safer medications such as Paracetamol, Ibuprofen, and Naproxen. With the usual dosage that a doctor may prescribe, the amount of drug excreted into breast milk is very less. However, medical data regarding Tramadol use during breastfeeding found numerous cases of excessive sleepiness and serious breathing difficulties, including one baby’s death, in babies of breastfeeding mothers taking Tramadol. The FDA advises breastfeeding mothers and caregivers to watch closely on the baby for signs of problems when the mothers are using any opioid pain medicine, especially when they are using Tramadol for pain.
