Clomiphene, commonly known as Clomid or Serophene, is a medication primarily used to address irregular or absent ovulation in individuals seeking pregnancy. As a selective estrogen receptor modulator (SERM), Clomid works by influencing the hormonal balance in the body, ultimately promoting ovulation and increasing the likelihood of conception. While Clomid is widely recognized for its fertility-enhancing properties, it's important to consider its potential side effects and its surprising impact on weight management.
What is Clomid and How Does It Work?
Clomiphene citrate (Clomid) is a non-steroidal fertility medicine. Clomid is classified as a selective estrogen receptor modulator (SERM). It functions by interacting with the body’s hormonal system to stimulate ovulation. It works by binding to estrogen receptors in the hypothalamus, a crucial part of the brain that regulates hormones. By blocking estrogen receptors in the brain, Clomid tricks the body into thinking estrogen levels are low. As a result, the body produces more gonadotropins, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), vital for stimulating testosterone and sperm production. Elevated levels of FSH encourage the ovaries to develop multiple follicles, each containing an egg. As the follicles mature, they release increasing amounts of estrogen, which eventually triggers a surge of LH. This surge prompts the release of an egg, making ovulation possible.
While primarily prescribed to women, Clomid can also be used off-label to treat male infertility by increasing sperm count and improving testosterone levels.
Uses of Clomid
Clomiphene is used as a fertility medicine in some women who are unable to become pregnant. Clomiphene probably works by changing the hormone balance of the body. Besides the known effect of massive obesity in inducing a partial hypogonadotropic hypogonadism, others factors appear to be involved in causing lowered T levels in this condition, in particular: i) insulin resistance, ii) abnormal adipokine and cytokine release, iii) chronic hypothalamus inflammation, and iv) increased estradiol (E2) production [5]. How to restore normal circulating T levels in these patients is still under debate. Weight loss, whether obtained by life style measures, eventually in association with insulin sensitizer drugs [10-12] or by bariatric surgery [13] has been proven to markedly increase T levels. Some new approaches, finalized at restoring endogenous T production in these patients with functional hypogonadism, are represented by aromatase inhibitors or selective estrogen receptor modulator (SERM).
Clomiphene may also be used for other conditions in both females and males as determined by your doctor.
Read also: Weight Loss Guide Andalusia, AL
Dosage and Administration
Clomid is usually prescribed as a pill that is to be taken for 5 days out of each month or cycle. Take this medicine only as directed by your doctor. If you are to begin on Day 5, count the first day of your menstrual period as Day 1. Beginning on Day 5, take the correct dose every day for as many days as your doctor ordered. To help you to remember to take your dose of medicine, take it at the same time every day. Typically, doctors will start patients on Clomid anywhere from Day 2 to 5 of their cycle and then taking it for five consecutive days in a row. A usual starting dose is about 50 mg per day but doctors can titrate it upwards to 100 mg or even 150 mg per day.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
For oral dosage form (tablets): For treating infertility: Adults-50 milligrams (mg) a day for five days of a menstrual cycle. The treatment is usually started on the fifth day of your menstrual period. If you do not have menstrual cycles, you can begin taking your medicine at any time. If you do not become pregnant after the first course, your doctor may increase your dose a little at a time up to 250 mg a day. Your treatment may be repeated until you do become pregnant or for up to four treatment cycles.
It is very important that your doctor check your progress at regular visits to make sure this medicine is working and to check for unwanted effects. At certain times in your menstrual cycle, your doctor may want you to use an ovulation prediction test kit. Follow your doctor's instructions carefully. Ovulation is controlled by luteinizing hormone (LH). LH is present in the blood and urine in very small amounts during most of the menstrual cycle but rises suddenly for a short time in the middle of the menstrual cycle. This sharp rise, the LH surge, usually causes ovulation within about 30 hours. A woman is most likely to become pregnant if she has intercourse within the 24 hours after detecting the LH surge. Ovulation prediction test kits are used to test for this large amount of LH in the urine. This method is better for predicting ovulation than measuring daily basal body temperature. It is important that intercourse take place at the correct time to give you the best chance of becoming pregnant.
Clomid's Impact on Weight Loss
Interestingly, Clomid may also have an unexpected side effect-weight loss. Clomid can be an effective treatment for male infertility, and for many men, it brings the added benefit of improving weight management. While weight loss is not the primary purpose of Clomid, many men experience positive changes in their body composition as a result of the medication. With its ability to increase testosterone production and balance hormone levels, Clomid may help with muscle growth, energy levels, and the reduction of stubborn belly fat.
Read also: Beef jerky: A high-protein option for shedding pounds?
How to Know if Clomid is Working for Weight Loss
For most men undergoing Clomid treatment, the primary indicators that Clomid is working are related to fertility. You may notice changes in your sperm count and testosterone levels as the medication stimulates the production of these vital hormones. But when we look through the lens of weight loss, there are a few other signs that might suggest Clomid is having a positive impact:
- Increased Energy Levels: One of the first signs that Clomid is working is a noticeable improvement in your energy levels. Clomid works to balance your hormones, and higher testosterone levels can give you more stamina and vitality. With more energy, you may find it easier to stay active, which naturally leads to weight loss.
- Improved Muscle Mass: Another way to measure Clomid’s effectiveness from a weight loss perspective is by looking at your body composition. With increased testosterone levels, many men experience an increase in muscle mass. Muscle burns more calories at rest compared to fat, which can lead to weight loss over time. If you’re noticing more definition in your muscles or an increase in strength, it could be a sign that Clomid is boosting your metabolism and supporting weight management.
- Reduction in Belly Fat: Weight loss, particularly the loss of stubborn belly fat, is a common challenge for many men. Testosterone plays a crucial role in fat distribution in the body, and when Clomid increases your testosterone levels, you may notice a reduction in the fat around your midsection. As your body begins to balance hormones, you may see a gradual decrease in visceral fat, which can harm your health.
- Better Mood and Motivation: Clomid’s effect on testosterone levels doesn’t only influence physical changes but also has an impact on your mood. Many men on Clomid report a noticeable improvement in their mood and a reduction in feelings of depression or anxiety, which can often accompany low testosterone. When you feel better mentally, you’re more likely to make healthier choices and stay motivated to maintain a healthy lifestyle, contributing to weight loss.
- Appetite Regulation: Testosterone can also influence your appetite. Many men notice that, with increased testosterone, their appetite is better regulated. This can result in healthier eating habits, which play a key role in achieving and maintaining weight loss.
The Role of Testosterone
Testosterone plays a crucial role in fat distribution in the body. When Clomid increases testosterone levels, men may experience a reduction in fat around their midsection and a decrease in visceral fat. Additionally, increased testosterone levels can lead to increased muscle mass, boosting metabolism and supporting weight management.
Low testosterone levels are noted to increase weight gain due to adipose tissue, and increasing testosterone levels are an effective adjunct treatment for weight loss in most men. Increases in lean muscle mass are noted in men with improved testosterone levels who are exercising, and muscle weighs more than fat (which can increase overall weight as well).
Clomid and Metabolic Parameters
In men, hypogonadism is generally regarded as a clinical condition which might yield and underpin obesity, metabolic syndrome (MS) and even overt type 2 diabetes mellitus (T2DM) [1,2], regardless of where (i.e. at hypothalamic, pituitary and/or testicular levels) and when it onsets (pre-pubertal or post-pubertal onset). On the other hand, men affected by metabolic disorders have low serum testosterone (T) levels [3] whose levels could vary according to individual MS components (i.e. hypertrigliceridemia, abdominal obesity and glycaemia, etc) [4]. Several mechanisms are known to interfere with the hypothalamic-pituitary-gonadal (HPG) axis and thus be responsible for low T level production in obese dysmetabolic patients [5].
During Clomid treatment, there is a tendency towards a decrease in both BMI and waist circumference, and a significant reduction of fasting glucose and insulin levels, and in the HOMA-IR, whereas no significant changes occur in either HbA1c or leptin levels.
Read also: Inspiring Health Transformation
Potential Side Effects of Clomid
While Clomid is generally well-tolerated, it's essential to be aware of potential side effects.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
The most common effects are mood swings, which affect more than 50% of people, and hot flashes, which happen in about 20%. A smaller number report breast tenderness, nausea, pelvic pressure, or headaches.
Common Side Effects
- Hot flashes
- Mood swings and increased irritability
- Breast pain or tenderness
- Headache
- Irregular menstrual cycles or spotting
- Nausea
- Bloating
Less Common, but More Serious Side Effects
- Ovarian Hyperstimulation Syndrome (OHSS): A condition where the ovaries become excessively stimulated, leading to swollen and painful ovaries. Symptoms can include severe abdominal pain, rapid weight gain, shortness of breath, and decreased urination.
- Change in vision: Less commonly, Clomid may cause vision changes, such as blurred or double vision, light sensitivity, or small blind spots. Because rare cases of lasting vision symptoms have been reported, it’s important to tell your fertility doctor right away if this happens to you.
- Allergic reactions: skin rash, itching, hives, swelling of the face, lips, tongue, or throat
- Pancreatitis: severe stomach pain that spreads to your back or gets worse after eating or when touched, fever, nausea, vomiting
Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not clear-headed or able to see well. If these reactions are especially bothersome, check with your doctor.
Side Effects in Men
Clomiphene has a very good safety profile in men using it for fertility purposes. A meta-analysis of studies on this patient population showed no serious adverse events. [Huijben M. Andrology 2023] Though clomiphene has a bad reputation in women (since it can provoke significant mood swings in some women who use it, men do not seem to experience this same side effect profile. In fact, low T symptoms are often improved in men taking clomiphene for hypogonadism.
In the above mentioned meta-analysis, about 2.27% of men reported mild adverse side effects such as headache, gynecomastia (which should not occur if estradiol levels are being followed appropriately), dizziness, visual changes, mood changes, and fatigue. Another review of 393 men taking clomiphene for an average of 2.5 years reported a rate of 9% for adverse side effects. [Krzastek SC. JUrol 2019] These included mood changes (2.3%), blurred vision (1.8%), breast/nipple tenderness (1.5%), weight gain (1.3%) and acne (0.5%).
Considerations for Men on Clomid
- Mood changes: Adverse mood changes can occur. However, this must also be weighed against the finding in this study that 78% of men reported an overall improvement in their low-testosterone symptoms.
- Visual disturbances: Blurred vision, spots in vision, and flashes of light are the most common side effects that doctors have seen in men taking clomiphene, although they only occur in a small number (less than 2 percent) of them. Generally, the visual side effects resolve within a few weeks of lowering the dosage or stopping the medication. Men with a history of central retinal vein occlusion (CRVO) should consult with their ophthalmologist before starting SERMs.
- Breast/nipple tenderness: This side effect is generally related to estradiol levels which are too high and should be rare if estradiol levels are followed and kept within the normal range.
- Weight gain: Typically, this is minimal. Some men have reported some mild fluid retention which can cause some weight gain.
- Acne.
Multiple Pregnancies
One of the notable risks of Clomid treatment is its impact on the likelihood of multiple pregnancies, particularly twins. Studies indicate that the incidence of twin pregnancies with Clomid ranges from approximately 5% to 12%. This is significantly higher than the natural twinning rate of about 1-2% without the use of Clomid.
Compared to other fertility treatments, this medication does not greatly increase your chances of having multiple babies. An increased chance of having twins may occur in roughly 5 out of every 100 women who take this medication.
Alternative Treatments to Clomid for Male Fertility
While Clomid has proven effective for many men, it’s not the only option for increasing sperm count or improving testosterone levels. If Clomid isn’t providing the results you’re looking for, there are several alternative treatments to consider.
- Testosterone Replacement Therapy (TRT): For men who have low testosterone levels, TRT is often recommended as an alternative to Clomid. TRT can come in several forms, including injections, patches, or gels, and helps increase testosterone levels directly. While TRT is effective for boosting testosterone, it can sometimes suppress sperm production, so it may not be the best option for men trying to conceive.
- Human Chorionic Gonadotropin (hCG) Injections: hCG is a hormone that stimulates the production of testosterone and sperm. It’s sometimes used in combination with Clomid to boost fertility, especially in men with low sperm counts. hCG injections are often used when Clomid alone doesn’t yield the desired results.
- Lifestyle Changes: Sometimes, addressing lifestyle factors such as diet, exercise, and stress levels can significantly affect male fertility. Weight loss, improved nutrition, and regular exercise can boost testosterone production and improve sperm count. For men dealing with obesity or excess belly fat, losing weight can have a profound effect on fertility and overall health.
- Surgical Options: In some cases, male infertility is caused by a physical issue, such as a varicocele (enlarged veins in the scrotum) or a blockage in the reproductive tract.
Alternatives to Clomid for Women
Luckily, Clomid is but one drug that can be used to treat unexplained infertility. Another popular alternative to Clomid is a drug called Letrozole.
Precautions and When to Avoid Clomid
There is a chance that clomiphene may cause birth defects if it is taken after you become pregnant. Stop taking this medicine and tell your doctor immediately if you think you have become pregnant while still taking clomiphene.
For women who have liver disease, are breastfeeding, have undiagnosed uterine bleeding or ovarian cysts, Clomid should not be taken due to the risks it poses for those with those conditions.
Other SERMs
Selective estrogen receptor modulators (SERMs) are medications that impact the function of different estrogen receptors throughout the body. There are 3 main SERMs used clinically for the management of male fertility:
- Clomiphene citrate (Clomid)
- Tamoxifen (Nolvadex, Soltamox)
- Enclomiphene (Androxal)
The ability of SERMs to increase testosterone levels is roughly comparable to that of testosterone gels and has the ability to increase libido, energy and sense of well-being in hypogonadal men. [Katz DJ. BJUI 2012] A long term (mean follow-up 4.5 years) study of 120 men on clomiphene noted sustained normalization of testosterone levels in 88% of men with improvement in their hypogonadal symptoms in 77%. [Krzastek SC. JUrol 2019]
Tamoxifen (Nolvadex, soltamox)
Tamoxifen is a SERM that historically has been used its ability to inhibit the stimulatory effect of estrogens on breast tissue. It has therefore found a role in the management of estrogen-receptor positive breast cancer as well as gynecomastia. In terms of male fertility, the mechanism of action is the same as with clomiphene, namely antagonism of the function of estrogen receptors in the pituitary gland which thereby increases the release of LH and FSH. [Wibowo E. Andrology 2016]
Multiple randomized controlled trials over the years have shown the ability of tamoxifen to improve sperm counts and motility in men with hypogonadism and abnormal semen parameters. [Cakan M. UrolInt 2009][Kotoulas I. FertSteril 1994][Maier U. EurUrol 1988]
The current 2024 cheapest listed price on GoodRx.Com for a month of brand name tamoxifen (10mg twice daily) is $14.08. Price is one of the primary drivers of increased use of tamoxifen in the treatment of male fertility because in 2023 generic clomiphene became unavailable. In 2020, a month’s supply of generic clomiphene (50mg every other day) could be purchased on GoodRx for $17.99- now that same prescription for brand name Clomid is listed for $67.50.
Enclomiphene (androxal)
Biochemically, clomiphene is made up of 2 stereoisomers (defined as molecules with the same composition but just with their atoms lined up in different patterns). 62% of clomiphene is made up of the stereoisomer enclomiphene which has more anti-estrogenic effect, while 38% is zuclomiphene which has more estrogenic effects. Androxal was produced by a process which isolated just the enclomiphene component while not including the zuclomiphene element in an attempt to produce a medication with a bigger potential impact on fertility with fewer side effects. Studies have confirmed that enclomiphene has the ability increase the production of LH and FSH in men as well as testosterone levels similar to that of clomiphene. [Wiehle R. BJUI 2013]. Studies have also shown improvements in sperm counts and motility with the use of enclomiphene in men with hypogonadism and fertility issues. [Thomas J. Cureus 2023].