Clomiphene or Clomid is used in the treatment of oligomenorrhea. Oligomenorrhea is a condition where a woman gets infrequent or light menstrual periods. The drug was introduced in 1960s. However, once it was approved, many medical practitioners found out that this drug increased the chances of fertility mainly due to ovulation’s induction. This information led to an investigation that Clomid could be potentially used as a treatment for infertility, which as it was assumed, was found effective. Even now, Clomid is one of the most popular medications for anovulation’s reversal. The chemical composition of Clomid includes two isomers – zuclomiphene and enclomiphene. Both of these act as SERM (selective estrogen receptor modulator). To be precise, these isomers get bound to the receptor sites of estrogen in the form of competitive antagonists, thereby preventing estrogen’s negative feedback on the release of gonadotropin.
This leads to yielding of increased hypothalamic-pituitary-gonadal axis (HPG) activation. It ultimately stimulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) for inducing ovulation. However, even though it has high efficiency for inducing ovulation, some users have complained of some adverse side effects like headaches, abnormal bleeding, vision changes and enlarged ovaries. Some of them have also had concerns of usage of Clomid leading to ovarian cancer. For this very reason, many people have stopped taking Clomid and also wondered as to how long it actually stays in their body once taken.
How Long Does Clomid Stay In Your System ?
First things first, you need to know that if you have just stopped taking Clomid, you might experience some side effects for a few days or in the worst case scenario, even for a few weeks post the last dose. This will understandably make you feel that Clomid or its metabolites are still present in your body and would want to know for how many days they will be there. To find that out, we need to know its elimination half life which is about 5 to 7 days. This means that it should take about a week after your last dose to eliminate about half of the Clomid dose from your body. Since Clomid has such a long elimination half life, it is possible that you are right about Clomid still being in your system, weeks after your last dose. On an average, it takes anywhere between 27.5 days to 38.5 days for complete elimination of Clomid from your system, meaning, around 4-6 weeks.
There are some other reports as well which claim that Clomid’s half life is about 2 weeks, which means that it could stay up to 11 weeks in your body post the last dose. For most users, they can expect Clomid to stay in their systemic circulation for anywhere between 1 to 3 months post the final dose. Clomid is made of these isomers – zuclomiphene (~38%) and enclomiphene (~62%). The elimination half life of zuclomiphene is longer than that of enclomiphene, which is 24 hours. Enclomiphene is estimated to be eliminated in a week whereas zuclomiphene stands responsible for a longer elimination time of Clomid. Zuclomiphene has shown to appear in plasma even after a month’s Clomid discontinuation; the remaining amounts tend to be excreted out via feces 6 weeks later.
- Factors influencing the stay of Clomid in your body:
We now know that Clomid stays in our system for about 4 weeks to 11 weeks after the final dose, but not everyone will eliminate it at the exact same speed. Some people tend to eliminate out zuclomiphene and enclomiphene faster than the usual time while others can have zuclomiphene in their bodies even after six weeks. There are various factors which influence the elimination time. They are listed below:
Administration term and cycles:
According to the medical instructions, Clomid is to be taken for 5 days consecutively which will trigger the ovulation in the next 5 days to 9 days. Some people take Clomid for a shorter duration while some take it for a longer duration than the ideal 5 days – all of these are based on the doctor’s prescription. So, logically, the shorter your duration for Clomid intake is, the shorter time it will take to be out of your system. Similarly, if your term for administration is longer, you can expect it to stay for a longer time, particularly, zuclomiphene. For example, for someone who has taken 50 mg dose for 4 days, she will have taken about 200 mg Clomidand will obviously eliminate it out faster than someone who has taken the same dose, but for 6 days, meaning 300 mg Clomid.
Therefore, the longer your term of administration is, the longer it will take for the metabolism and excretion of your last dose. Now this delayed metabolism along with more Clomid quantity leads to an increased elimination time as compared to someone who takes it for a shorter time. Moreover, the how many cycles passed during this interval of administration of Clomid are also to be considered. For the people who have taken it for more cycles might be asked to increase the dosages for consecutive cycles, Moreover, if Clomid is taken for over one cycle, it means that the dose from the previous intake would still be present in the plasma of the user. Since we know that the complete elimination of the plasma could take about 3 months, taking Clomid for more cycles could lead to greater accumulation in the body. This in turn leads to an even longer elimination time as compared to someone who has taken it for just a cycle or two.
The amount of daily dosage:
The amount of daily dosage of Clomid will affect as to how long it will stay in your body once you have discontinued it. For example, if you have take 50 mg dose, it would be eliminated much quicker than if you have taken a 250 mg dose. Here’s the thing – After about 5 -7 days of discontinuing 250 mg, there would still be about 125 mg in your system, but after discontinuing 50 mg dose, there would just be about 25 mg in your system. Hence, if you happen to take a higher dose, more amount of Clomid will stay in your plasma for a longer time, than a lower dose. Moreover, it should also be noted that a higher dose will put some more burden on your hepatic pathways which are actually responsibole for the metabolism of Clomid. Why this happens is that more Clomid amount makes is it necessary for its hepatic metabolism. But the thing is , the isoenzyemes can metabolize only a certain amount of drug at a given time.
After this quantity gets increased beyond the threshold capacity, the metabolism efficiency is compromised and it takes more time to break down Clomid. When there is a high dose take, more quantity of zuclomiphene and enclomiphene will enter the systemic circulation. Clomiphene isomers’ increasing amount in the circulation leads to a higher accumulation of the isomers in the tissues and ultimately leads to enterohepatic recirculation. Furthermore, the higher doses can also get accumulated in the excretion pathways and even there if the level goes beyond its threshold capacity, excretion efficiency will be compromised. Hence, if you take a standard 50 mg dose of Clomid, you know that its metabolism and excretion will be carried out more efficiently than if you were to take any higher doses. With every doubled dose, you can expect the half life elimination to be increased.
Other individual factors:
Consider a hypothetical situation where 2 women have simultaneously taken the same 50 mg Clomid dose for 5 days continuously during early time of their individual menstrual cycles. Even then, both of them will eliminate the Clomid out at different rates. Why is there a difference in the elimination time even when all the factors were similar? That’s because the individual factors of both of them come into picture. These include – genetic, hepatic function, body mass and age. Let’s take a look at how each of them affects it:
- Renal function: the renal function of a person can have some influence on the speed at which the drug is excreted out the body. Even though renal pathways do not play a greater role in the elimination of Clomid, they excrete about 8% of its dose. Hence, people with different levels of impairment of renal function will not be able to eliminate the small amounts more efficiently. In fact, renal impairment influences the efficiency of many drugs’ elimination, thereby leading to some accumulation along with re-absorption in your plasma. Milder degrees of renal impairment would not cause any major impact on the elimination, but a more severe impairment could have a longer effect on the elimination of the drug. Therefore, if you have renal impairment, you are more likely to have Clomid for a bit longer in your body as compared to someone who has a normal kidney function.
- Hepatic function: For those people who have any kind of hepatic impairment, taking Clomid should be altogether avoided. However, if you ignore this and do take Clomid, there would be an abnormally high level of clomiphene in your plasma concentration. This happens because the functionality of liver isoenzymes (like CYP2D6) is interfered if there is a hepatic impairment. This in turn leads to a poor metabolism. How much a person’s hepatic impairment is will decide the elimination half life of clomiphene. For someone with a more severe impairment of hepatic function, clomiphene and their metabolites will stay for a much longer period of time than someone who has a normal hepatic function. For someone with just a mild impairment of hepatic system, clomiphene will stay for just a little longer than usual. Moreover, the half life elimination of some other selective estrogen receptor modulators (SERMs) will be doubled if the drug is administered in person with an impaired hepatic function. If something like this were to be found for Clomid, it would stay in the person’s system for anywhere between 8 weeks to 22 weeks once it is discontinued. The more severe the hepatic impairment is, the longer it will take for the elimination of Clomid from body.
- Sex: Even though women use Clomid for inducing ovulation, it is also used by some men for the treatment of hypogonadism. Now since men also use it, it can be understood that there are going to be difference, sex specific, for pharmacokinetics of Clomid. Men can show changed concentrations of plasma or changed volumes of distribution as compared to females, which leads to a difference in the elimination half lives.
- Body mass and fat %: Clomid is known to bind with the plasma proteins and it also has the propensity for accumulation in the fatty tissues of the body. Hence, the distribution of metabolites of Clomid and Clomid itself will vary for people with different BMIs. Women who are obese or have a high fat percentage tend to get higher levels of Clomid accumulation because of the presence of more fatty tissues and also because of the fact that they are highly likely to take higher doses. Why do obese women take higher dose? That’s because they have greater androgen levels as compared to slimmer women. Now this high dose when combined with more fatty acid which enables more accumulation could lead to a longer elimination half life. This happens especially if it is taken for longer duration of time. If you happen to have high fat percentage in your body, you would require Clomid’s supratherapeutic dose and hence it is possible that it will stay for much longer time once you discontinue it.
- Metabolic rate: A person’s Basal Metabolic Rate – BMR can also influence the stay of Clomid in the body once it is discontinued. For the people who have high BMR, they tend to burn more energy and are known to excrete out the exogenous substance quicker than the people with lower BMRs. So if you happen to have high BMR, you should know that the metabolism and excretion of Clomid will be faster than the average time. Now, BMR is also linked with the body fat amount in a person. So a person with high BMR has low body fat and vice versa. What happens with more fatty tissues in the body is explained in the above point. Hence, it can be said that BMR affects the elimination of Clomid indirectly through influencing a person’s body fat and BMI.
- Genetics: Clomid is said to undergo extensive hepatic metabolism, according to medicine. Even though the hepatic pathways which are responsible for the metabolism of Clomid are not completely elucidated, there in one pathway which plays an important role – CYP2D6 (cytochrome P450 2D6). CYP2D6 is a highly polymorphic gene. So, about 3 to 10% people can carry CYP2D6 alleles which are not functional, and it can result in poorer metabolism of Clomid. Pooer metabolism of CYP2D6 will lead to a failure of yielding necessary metabolites for inducing ovulation. It also causes accumulation of clomiphene’s plasma concentrations and thereby increasing its elimination half life. Now ultrarapid CYP2D6 metabolizers are considered to carry many functional alleles of CYP2D6 which results in a quicker clomiphene metabolism and enough metabolites concentrations for inducing ovulation. Hence, Ultrarapid CYP2D6 metabolizers might help your body to eliminate Clomid out from your systemic circulation faster than the average speed. Most of the Clomid users – about 70% of them can be considered as extensive metabolizers as they have one functional allele of CYP2D6. In such cases, the metabolism and excretion of the drug is carried out at the normal pace. Genesight is a test you could take to know what level of Clomid metabolizer you are.
- Other drugs: Clomid is known to undergo the hepatic metabolism through CYP2D6 isoenzymes, so, chances are, if there is a co administration of other drugs, the altered functionality of CYP2D6 can affect the pharmacokinetics. To be more specific, the drugs which are co ingested if inhibit the function of CYP2D6; Clomid’s elimination will take a longer time. If those drugs happen to induce the function of CYP2D6, the elimination process of Clomid will be boosted. Some coomon examples of CYP2D6 inhibitors are: Ritonavir, Cinacalcet, Paroxetine, Bupropion, Fluoxetine and Quinidine. Therefore, if you end up taking Clomid along with an inhibitor of Quinidine, its metabolism is going to be compromised which will lead to an elevation in the plasma level and ultimately, a longer time in elimination. On the other hand, if you take up an inducer of CYP2D6 along with Clomid, it will be metabolized quickly and its elimination process will be expedited. Some of the commone examples of CYP2D6 inducers are – Rifampicin, Glutethimide, Promethazine and Dexamethasone. However, it is important to note that the level to which a co administered drug will either inhibit or induce CYP2D6 will depend on the drug itself and its dosage.
Easy ways for clearing Clomid from the system:
If you take Clomid and want to get it eliminated from your body effectively, there are some things you could do to make sure it happens on time. However, if you are seriously planning to do something for the expedition of the process of Clomid elimination, it is of utmost importance that you consult a doctor. Their suggestions and feedback can always provide better benefits of detoxification than anything else. Have a look at some of those tips:
- Exercise: Since we already know that Clomid is lipophilic and is known to get accumulated in the fatty tissues of the body, exercising could help burning of the extra fat and thereby harbor the metabolites of clomiphene and clomiphene itself. Even though regular exercise won’t have any high impact on the elimination process, it could make the expedition of the process slightly easier. You could either go for a quick jog or indulge in some cardio exercise for burning some fats and helping the body excrete out Clomid quickly.
- Calcium-d-glucarate: A tiny amount of clomiphene, almost 8% is thrown out of the body through the kidneys. Now your kidneys don’t really need any help for throwing out such a small amount, but calcium-d-glucarate’s supplements could elevate renal excretion. Calcium-d-glucarate acts as an inhibitor of beta-glucuronidase, and hence helps clear out the built up molecules in the pathways of renal detoxification. Thus, the 8% of clomiphene to be renally excreted could be done at a quicker rate by using calcium-d-glucarate.
- Activated charcoal: activated charcoal always acts as great supplement when you are trying to detox your body from any drugs. It will bind to the unmetabolized substances along with binding to endotoxins which might have been formed due to Clomid’s administration. Even though activated charcoal will not leave any major impact on Clomid elimination, it will definitely help in the detoxification post treatment.
The process of absorption, metabolism and excretion of Clomid – explained:
Once Clomid is orally administered, clomiphene, the active ingredient gets rapidly absorbed through the GI tract (gastrointestinal). The isomers of clomiphene – (38%) zuclomiphene and (62%) enclomiphene are subjected for hepatic metabolism. According to some studies, both of these isomers are highly likely to be metabolized through CYP2D6 isoenzymes and they yield metabolites including (E)-4-hydroxy-N-desethylclomiphene and (E)-4-hydroxyclomiphene. These are the metabolites which are responsible for most of the estrogenic receptor competitive antagonism. Once zuclomiphene and enclomiphene are metabolized, theyextensively bind to plasma proteins and get distributed, including their respective metabolites. Plasma concentrations should peal after 6 hours of ingestion. The metabolites and isomers of Clomiphene get accumulated in the fatty tissues and are thought of exhibiting a great degree for lipophilicity.
Enclomiphene isomers have an elimination half life of about 5 days and zuclomiphene’s elimination half life is comparatively longer. Clomiphene‘s elimination half life is reported to be anywhere between 5 and 14 days. Most of the enclomiphene gets eliminated in about 28 days post the last dose and zuclomiphene gets eliminated in about 77 days. These differences in the elimination of the isomers is there because of an elevated propensity of zuclomiphene‘s enterohepatic recirculation. The metabolites of zuclomiphene are most commonly found in feces collected after 6 weeks post a single dose of Clomid. About 50% clomiphene is excreted out through feces and about 8% is excreted out through renal pathways.
