clomid
| Product dosage: 100mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 10 | $5.52 | $55.23 (0%) | 🛒 Add to cart |
| 20 | $3.77 | $110.46 $75.31 (32%) | 🛒 Add to cart |
| 30 | $2.85 | $165.68 $85.35 (48%) | 🛒 Add to cart |
| 60 | $1.67 | $331.37 $100.41 (70%) | 🛒 Add to cart |
| 90 | $1.23 | $497.05 $110.46 (78%) | 🛒 Add to cart |
| 120 | $1.09 | $662.73 $130.54 (80%) | 🛒 Add to cart |
| 180 | $0.84 | $994.10 $150.62 (85%) | 🛒 Add to cart |
| 270 | $0.78 | $1491.15 $210.87 (86%) | 🛒 Add to cart |
| 360 | $0.71
Best per pill | $1988.20 $256.06 (87%) | 🛒 Add to cart |
| Product dosage: 25mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 20 | $2.76 | $55.23 (0%) | 🛒 Add to cart |
| 30 | $2.18 | $82.84 $65.27 (21%) | 🛒 Add to cart |
| 60 | $1.34 | $165.68 $80.33 (52%) | 🛒 Add to cart |
| 90 | $1.00 | $248.53 $90.37 (64%) | 🛒 Add to cart |
| 120 | $0.84 | $331.37 $100.41 (70%) | 🛒 Add to cart |
| 180 | $0.64 | $497.05 $115.48 (77%) | 🛒 Add to cart |
| 270 | $0.48 | $745.58 $130.54 (82%) | 🛒 Add to cart |
| 360 | $0.43
Best per pill | $994.10 $155.64 (84%) | 🛒 Add to cart |
| Product dosage: 50mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 10 | $4.52 | $45.19 (0%) | 🛒 Add to cart |
| 20 | $3.26 | $90.37 $65.27 (28%) | 🛒 Add to cart |
| 30 | $2.51 | $135.56 $75.31 (44%) | 🛒 Add to cart |
| 60 | $1.51 | $271.12 $90.37 (67%) | 🛒 Add to cart |
| 90 | $1.12 | $406.68 $100.41 (75%) | 🛒 Add to cart |
| 120 | $0.88 | $542.24 $105.44 (81%) | 🛒 Add to cart |
| 180 | $0.73 | $813.36 $130.54 (84%) | 🛒 Add to cart |
| 270 | $0.65 | $1220.03 $175.73 (86%) | 🛒 Add to cart |
| 360 | $0.60
Best per pill | $1626.71 $215.89 (87%) | 🛒 Add to cart |
Synonyms
| |||
Clomiphene citrate, commonly known by its brand name Clomid, represents one of the foundational oral medications in reproductive medicine. As a selective estrogen receptor modulator (SERM), it occupies this unique niche where it paradoxically blocks estrogen receptors in the hypothalamus, leading to increased gonadotropin-releasing hormone (GnRH) secretion, which subsequently stimulates the pituitary gland to release more follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This cascade ultimately promotes ovarian follicular development and ovulation in anovulatory women. Its significance lies not just in its mechanism but in its decades-long track record as a first-line treatment for ovulatory dysfunction, particularly in polycystic ovary syndrome (PCOS). Despite newer agents like letrozole gaining traction, clomiphene remains a workhorse due to its established efficacy, relative safety profile in appropriate candidates, and oral administration route that avoids injections. Understanding its proper application requires appreciating both its endocrine orchestration and its clinical limitations.
Key Components and Bioavailability of Clomiphene Citrate
Clomiphene citrate is administered orally in tablet form, typically containing 50 mg of the active compound per tablet. Chemically, it’s a nonsteroidal agent that exists as a racemic mixture of two isomers: enclomiphene (trans-clomiphene) and zuclomiphene (cis-clomiphene). The zuclomiphene isomer has a significantly longer half-life—up to several weeks—compared to enclomiphene’s few days, which contributes to its cumulative effects with repeated cycles. Bioavailability is reasonably high after oral ingestion, with peak serum concentrations reached within hours. It undergoes hepatic metabolism via cytochrome P450 enzymes, primarily CYP2D6 and CYP3A4, and is excreted predominantly in feces. The drug’s lipophilic nature allows it to cross the blood-brain barrier readily, which is crucial for its central action on hypothalamic estrogen receptors. No special formulations like piperine are needed for absorption enhancement, as its bioavailability is sufficient for clinical effect at standard doses.
Mechanism of Action of Clomiphene Citrate: Scientific Substantiation
The primary mechanism, as touched on earlier, involves competitive antagonism of estrogen receptors at the level of the hypothalamus. By blocking the negative feedback estrogen typically exerts, clomiphene tricks the body into perceiving low estrogen levels. This prompts increased pulsatile GnRH secretion from the hypothalamus, which in turn stimulates the anterior pituitary to secrete more FSH and LH. The elevated FSH promotes the recruitment and growth of ovarian follicles, while the mid-cycle LH surge triggers ovulation. It’s this elegant hijacking of the hypothalamic-pituitary-ovarian (HPO) axis that makes it so effective for anovulation. However, its anti-estrogenic effects aren’t limited to the brain; they also occur peripherally in tissues like the endometrium and cervix, which can paradoxically create hostile conditions for conception despite successful ovulation—a nuance many clinicians initially overlook. The drug doesn’t directly stimulate the ovaries but rather modulates the central regulatory system, making it dependent on an intact HPO axis for success.
Indications for Use: What is Clomiphene Citrate Effective For?
Clomiphene Citrate for Ovulatory Dysfunction
The primary FDA-approved indication is the treatment of ovulatory dysfunction in women desiring pregnancy. It’s particularly effective in WHO Group II anovulation, characterized by normogonadotropic normoestrogenic anovulation, most commonly seen in PCOS. In these patients, it induces ovulation in approximately 70-80% of cases, with cumulative pregnancy rates around 35-40% over 3-6 cycles.
Clomiphene Citrate for Unexplained Infertility
Though off-label, it’s commonly used in unexplained infertility, often combined with intrauterine insemination (IUI). The rationale is to enhance follicular development and potentially correct subtle ovulatory disturbances not captured in standard testing. Studies show modest improvements in pregnancy rates compared to timed intercourse alone in this population.
Clomiphene Citrate for Male Infertility
Interestingly, clomiphene has applications in male infertility, particularly for hypogonadotropic hypogonadism or other conditions with low sperm counts associated with hypothalamic-pituitary dysfunction. By increasing GnRH pulsatility, it can boost both FSH (spermatogenesis) and LH (testosterone production), though evidence is less robust than for female applications.
Clomiphene Citrate for Ovulation Induction in IVF Cycles
Sometimes used for mild ovarian stimulation in IVF protocols, especially in poor responders or for minimal stimulation IVF. However, its anti-estrogenic effects on the endometrium make it less ideal for fresh transfers in standard IVF, so it’s typically used in freeze-all cycles when employed.
Instructions for Use: Dosage and Course of Administration
Treatment typically begins on day 3, 4, or 5 of the menstrual cycle (spontaneous or induced) at 50 mg daily for 5 days. Ovulation generally occurs 5-10 days after the last dose. If ovulation doesn’t occur, the dose can be increased by 50 mg increments in subsequent cycles up to 150 mg daily, though many clinicians will reconsider the diagnosis or approach if 100 mg fails. Monitoring with transvaginal ultrasound and/or serum progesterone levels is recommended, particularly at higher doses or with risk factors for ovarian hyperstimulation syndrome (OHSS).
| Indication | Starting Dose | Maximum Dose | Duration | Timing |
|---|---|---|---|---|
| Anovulatory infertility | 50 mg | 150 mg | 5 days | Cycle days 3-7 or 5-9 |
| Unexplained infertility with IUI | 50-100 mg | 150 mg | 5 days | Cycle days 3-7 |
| Male infertility | 25-50 mg | 50 mg | 25 days on, 5 days off | Daily |
Treatment is usually limited to 3-6 ovulatory cycles due to diminishing returns beyond this point and theoretical concerns about long-term use. If pregnancy hasn’t occurred after 3-6 ovulatory cycles, reassessment is warranted.
Contraindications and Drug Interactions of Clomiphene Citrate
Contraindications include pregnancy (Category X), liver disease, abnormal uterine bleeding of undetermined origin, ovarian cysts unrelated to PCOS, and uncontrolled thyroid or adrenal dysfunction. It should not be used in women with primary ovarian insufficiency or those who are hypersensitive to clomiphene citrate. Significant drug interactions occur with medications that affect CYP450 enzymes—CYP2D6 inhibitors like fluoxetine may increase clomiphene levels, while CYP3A4 inducers like carbamazepine may decrease efficacy. Concomitant use with other fertility medications like gonadotropins requires careful monitoring due to increased risk of OHSS. Common side effects include hot flashes (10%), abdominal discomfort (7%), breast tenderness (2%), and visual disturbances (1.5%), the latter requiring immediate discontinuation. The multiple pregnancy rate is approximately 5-8%, predominantly twins.
Clinical Studies and Evidence Base for Clomiphene Citrate
The evidence base for clomiphene is extensive, dating back to the 1960s. A landmark 2014 Cochrane review of 28 randomized trials confirmed its superiority to placebo for live birth rates in women with PCOS (OR 5.6, 95% CI 1.6-19.6). The 1998 ESHRE Capri Workshop Group analysis demonstrated cumulative pregnancy rates of 35–40% over 3 cycles and 45–50% over 6 cycles in appropriately selected anovulatory women. More recent head-to-head trials with letrozole, particularly the 2014 NICHD-sponsored Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) study, showed letrozole had higher live birth rates (27.5% vs 19.1%) in PCOS patients, leading many to reconsider first-line agent choice. However, clomiphene remains extensively validated with over five decades of clinical use and hundreds of published studies encompassing tens of thousands of patients, giving it an evidence depth few fertility treatments can match.
Comparing Clomiphene Citrate with Similar Products and Choosing a Quality Product
When comparing clomiphene to letrozole, the main alternative for ovulation induction, key differences emerge: letrozole appears more effective in PCOS with higher live birth rates and possibly lower multiple pregnancy rates, while clomiphene may have better efficacy in non-PCOS anovulation. Clomiphene has more anti-estrogenic effects on the endometrium, potentially creating less favorable implantation environments compared to letrozole. Versus gonadotropins, clomiphene is oral, cheaper, and has lower monitoring requirements and OHSS risk, but gonadotropins typically achieve higher pregnancy rates per cycle. Generic clomiphene is widely available and generally equivalent to brand-name versions, with quality assurance coming from FDA oversight rather than specific brand selection. Patients should ensure their medication comes from licensed pharmacies with proper verification systems.
Frequently Asked Questions (FAQ) about Clomiphene Citrate
What is the recommended course of clomiphene citrate to achieve results?
Most successful pregnancies occur within the first 3-6 ovulatory cycles, with diminishing returns thereafter. Continuing beyond 6 cycles is generally not recommended without reevaluation.
Can clomiphene citrate be combined with metformin?
Yes, particularly in PCOS patients with insulin resistance, combination therapy may improve ovulation rates compared to either agent alone, though evidence for synergistic effects on live birth rates is mixed.
Does clomiphene citrate cause birth defects?
Extensive data suggests no significant increase in major congenital malformations above baseline population risk when used as directed prior to conception.
How quickly does clomiphene citrate work?
Ovulation typically occurs 5-10 days after the last pill, with menses following 14-16 days after ovulation if pregnancy doesn’t occur.
Can clomiphene citrate be used for women with regular cycles?
Sometimes, in unexplained infertility with documented normal ovulation, it may be used with IUI to potentially enhance follicular development, though evidence is less robust than for anovulatory indications.
Conclusion: Validity of Clomiphene Citrate Use in Clinical Practice
Clomiphene citrate maintains an important role in reproductive medicine despite evolving treatment landscapes. Its well-characterized mechanism, extensive safety database, oral administration, and cost-effectiveness secure its position, particularly as a first-line option in resource-limited settings or specific patient subgroups. While letrozole may offer advantages in certain PCOS populations, clomiphene’s decades of successful use and predictable response profile ensure its continued relevance. The risk-benefit profile remains favorable when used appropriately in well-selected patients with proper monitoring. For anovulatory women desiring conception, particularly those with WHO Group II ovulatory dysfunction, clomiphene citrate represents an evidence-based intervention with proven efficacy for achieving ovulation and pregnancy.
I remember when we first started using clomiphene back in the late 90s—we were so optimistic about its potential. There was this one patient, Sarah, 29 with classic PCOS features: hirsutism, irregular cycles stretching 60-90 days, and that classic polycystic ovarian morphology on ultrasound. We started her on 50mg, cycle days 5-9, fully expecting a response. Nothing happened. Upped to 100mg—still no dominant follicle. The fellow working with me wanted to switch to injectables immediately, but I had this gut feeling we were missing something. We checked her TSH again—normal. Prolactin—normal. Then we did the clomiphene challenge test, which showed a borderline elevated day 10 FSH. Not terrible, but suggestive of diminished ovarian reserve despite her age. We decided to try one more cycle at 150mg with estrogen priming in the luteal phase beforehand. Boom—three follicles developed, two over 18mm. She ovulated, and though she didn’t conceive that cycle, it told us her ovaries could respond with the right tweaking. She eventually did conceive on her fourth attempted cycle, though we’d moved to letrozole by then due to concerns about the endometrial thickness with clomiphene. What that experience taught me was that clomiphene isn’t just a simple pill you prescribe—it’s a diagnostic tool in itself. The way a patient responds, or doesn’t, tells you volumes about their hypothalamic-pituitary-ovarian axis integrity. We’ve had plenty of cases where poor response to adequate clomiphene dosing revealed unexpected issues like subtle hyperprolactinemia or even empty sella syndrome. On the flip side, I’ve seen patients develop 4-5 follicles on just 50mg, reminding us that individual sensitivity varies tremendously. The team sometimes debates whether we should abandon clomiphene entirely in favor of letrozole, especially after the PPCOS II trial data. But I’ve seen enough cases where clomiphene worked beautifully after letrozole failed, or where insurance coverage made clomiphene the only feasible option, that I believe it still deserves a place in our toolkit. One of my most memorable successes was a 34-year-old teacher with 5 years of unexplained infertility—normal cycles, normal semen analysis, patent tubes. We’d done three IUIs with clomiphene without success. She was about to move to IVF when I suggested we try one more clomiphene cycle but add low-dose dexamethasone to see if we could improve follicular response. She developed two beautiful 22mm follicles, had the IUI, and is now raising twin boys. Sometimes the old tools, with slight modifications, still work magic. We recently followed up with several patients from our early clomiphene cohorts—many now with teenage children—and the longitudinal data is reassuring. No increased cancer risks, their children developing normally. One mother told me last month, “That little white pill gave me my family when I thought it was impossible.” That’s why, despite the flashier new protocols, I still reach for clomiphene when the clinical picture fits.