Comparing Enclomiphene With Clomiphene, IVF, And TRT: Which Is Best For You?

Enclomiphene is a derivative of clomiphene meaning it is similar (but not identical) in structure and biochemical function. Clomiphene citrate works as an agonist, which can mimic or suppress estrogen in different tissues. In contrast, enclomiphene behaves as an antagonist competing against estrogen to bind to estrogen receptors.

In the hypothalamus, both molecules bind to estrogen receptors and result in an increase of gonadotropins (FSH and LH hormones). The increase of gonadotropins then stimulates hormone-mediated processes like ovulating in those assigned female at birth (AFAB) and testosterone production in those assigned male at birth (AMAB).

A key symptom and quality of life stressor associated with low testosterone in those AMAB is a decrease in fertility. A multitude of research has shown the clomiphene effectiveness and enclomiphene effectiveness for increasing testosterone.³ While both enclomiphene and clomiphene have success in increasing testosterone levels in those AMAB, enclomiphene has also been seen to have more consistent research in increasing sperm production as well.⁴ Recent comparative research suggests there are great benefits to enclomiphene that should be examined further.⁵

The common enclomiphene side effects as well as clomiphene side effects are often mild and infrequent. These side effects can include headaches, nausea, increase in libido, hot flashes, and joint pain. In addition to this are rare yet severe clomiphene side effects, such as allergic reactions, pancreatitis, and vision impairment.

Accessing hormonal treatments requires a review of the financial burden and availability. Both clomiphene and enclomiphene require a prescription to be bought. Costs associated with both medications are impacted by factors such as insurance coverage, reason for your prescription and your location. Enclomiphene costs can range from $50-150 depending on dosage, while clomiphene averages $180-200 for 30 tablets.

While enclomiphene citrate and IVF can both be paths to treat infertility, their mechanisms look very different biologically. Enclomiphene binds to the estrogen receptors in the hypothalamus inhibiting the estrogen feedback loop and increasing gonadotropins. Remember, a rise in gonadotropins leads to ovulation in people AFAB and testosterone production in people AMAB.

Alternatively, IVF brings eggs and sperm in direct contact, outside of the body, to achieve fertilization. After fertilization is achieved and the embryos have been monitored for development; the mature embryo is released into the uterus of those AFAB for implantation. When IVF is sought in response to issues with sperm, there is often an addition of an intracytoplasmic sperm injection. This procedure takes sperm from a semen sample or even directly from the testes to be inserted into the egg.

IVF is a well documented and researched procedure that has substantial data around its birth efficacy. In 2019, 46.7% of IVF egg retrievals resulted in live birth for individuals under 35. The success rate dropped to 3.2% for IVF transfers in those older than 42. Enclomiphene citrate has been identified as a successful treatment for low testosterone and possible benefits with maintaining sperm count and motility. However, more research is needed to determine its consistent impact on sperm and fertility.

Enclomiphene citrate and IVF also share some common side effects such as nausea, headaches, and hot flashes. IVF can have additional side effects that are unique to the birth parent and highly dependent on their medical history.

Evaluating the cost and accessibility of these treatments is going to vary greatly depending on your circumstances. For instance, where you live, what insurance you have, the prescribed reason for these treatments, and quantity are all important considerations. Enclomiphene citrate has an average cost ranging from $50-150 per prescription. IVF treatments have an even wider range, yet the national average sits around $14,000 for a full round (egg stimulation, fertilization and transfer).

Testosterone replacement therapy (TRT) and enclomiphene citrate have both been used to treat testosterone deficiency.⁶ Their mechanism of action, however, is different due to their biochemical makeup and function.

Enclomiphene citrate stops the estrogen feedback loop early in the pathway by binding to estrogen receptors inhibiting the signal. Estrogen inhibition increases gonadotropins levels and stimulates testosterone production.

In contrast, TRT is the synthetic replacement of the hormone testosterone which simply increases testosterone serum levels by directly adding more testosterone to the body.

Enclomiphene and TRT have notably different outcomes due to their differences in their biochemical behaviors. Research shows that both enclomiphene and TRT increase testosterone levels and are suitable treatments for different types of testosterone deficiency.⁷

However, TRT significantly increases testosterone levels and disrupts processes like sperm production through hormonal imbalance. Thus, enclomiphene is the more viable option for success in increasing testosterone levels and maintaining sperm efficacy.

Let’s look at the most notable differences in enclomiphene and TRT’s side effect profiles. While low sperm count and motility were mentioned; elevated testosterone levels have also been linked to an increased risk for blood clots, sleep apnea, and thickening of the heart.

Enclomiphene and testosterone are both medications which require a prescription. Like all treatments detailed in this article: their costs and accessibility are dependent on a combination of factors. Testosterone is available in forms such as pills, topical gels and injections. Enclomiphene’s average prescription range is $50-150, while testosterone’s average prescription can range from $40-600 depending on which form you chose to take.

Clomiphene and IVF are both options to address infertility in both those AFAB and AMAB. Yet, the treatments differ in their mechanism. Clomiphene agonistically binds to estrogen receptors in the hypothalamus, suppressing the estrogen feedback loop, and allowing for increased FSH and LH hormones. The rise in these gonadotropins results in testosterone production and ovulation in individuals AMAB and AFAB, respectively.

Clomiphene induces the body’s cellular pathways toward a hormonal shift favorable for reproduction. IVF, instead, combines eggs and sperm in a lab to induce fertilization and monitors for embryonic development. Once the embryo reaches maturation it is transferred to the uterus for implantation. Intracytoplasmic sperm injection is a procedure which takes sperm directly from semen or testes and injects it in the egg. Infertility cases involving poor sperm efficacy often require IVF paired with Intracytoplasmic sperm injection.

Research suggests clomiphene is a successful treatment for hormone-dependent issues such as poly-cystic ovarian syndrome, irregular menstruation, and testosterone deficiency.⁸ However, there isn’t a consensus on clomiphene’s fertility benefits in those AMAB.

IVF has a long history as a viable path for individuals experiencing fertility barriers. Recent data shows that for individuals AFAB; IVF has a success rate >40% for individuals if they are younger than 35. This rate drops below 4% in those AFAB who are 43 and older.

Clomiphene and IVF share the common mild fertility side effects of headaches, nausea, hot flashes and libido changes. Some severe and infrequent side effects of clomiphene are vision loss and rashes due to allergic reactions. IVF can hold specific yet serious side effects for the birthing parent depending on their age and medical profile which should always be considered.

Mechanisms and side effect profiles aren’t the only notable differences between these treatment options. While any number of factors can affect cost and accessibility, clomiphene is a generally cheaper option. Clomiphene’s average cost sits around $190. A single round of IVF including egg stimulation, fertilization and transfer averages around $14,000 nationally.

If you’re considering starting clomiphene or TRT you should understand how each works biochemically. TRT is a direct synthetic steroid replacement of the hormone testosterone. TRT introduces exogenous testosterone into the body’s system directly elevating testosterone levels and stimulating testosterone-regulated pathways.

Comparatively, clomiphene is a non-steroidal molecule that naturally stimulates the body’s production of testosterone through agnostically binding to estrogen receptors in the hypothalamus.

Examining clomiphene vs TRT as successful treatments is dependent on the desired outcomes. Findings show both clomiphene and TRT as very effective treatments combatting different forms of testosterone deficiency. Due to their different biochemical function and mechanisms they are not equally suitable for individuals with fertility concerns. Clomiphene’s ability to stimulate testosterone’s natural production may be linked to its possible fertility benefits.

Like all hormonal treatments clomiphene and TRT share some common side effects including changes in libido, headaches, and nausea. Elevated levels of testosterone are associated with cardiac hypertrophy, decreased sperm efficacy and fertility.⁹ Clomiphene also has severe, albeit uncommon side effects, such as pancreatitis and vision loss which should be weighed thoroughly.

The obtainability and financial costs associated with both testosterone and clomiphene are impacted by location, insurance coverage, dosage and brand. Testosterone’s availability is also widened by its multiple forms of administration including orally, injection, and topicals (patches, gels, etc.). Testosterone and clomiphene both require a prescription; with testosterone’s average cost between $40-600 and clomiphene’s average cost between $50-150.