Meta Information
ID:enclomiphene
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene is a selective estrogen receptor modulator that can interfere with fetal development and is strictly contraindicated during pregnancy.
Actionable advice:
This should not be used during pregnancy or when planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Pregnancy Category X. Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate does not offer benefit in this population.
Label source:
FDA label: Clomiphene Citrate (Clomid) [class-derived from: clomiphene]
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if enclomiphene passes into breast milk, but due to its hormonal effects, it is contraindicated during lactation.
Actionable advice:
This should not be used while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
caution should be exercised if clomiphene citrate is administered to a nursing woman. In some patients, clomiphene citrate may reduce lactation.
Label source:
FDA label: Clomiphene Citrate (Clomid) [class-derived from: clomiphene]
Action type:
avoid
Target id:
/condition/history-thromboembolism
Target name:
History of Blood Clots (DVT/PE)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Drugs in the SERM class have been associated with an increased risk of blood clots (thromboembolic events). Use is contraindicated in individuals with a history of such events.
Actionable advice:
This should be strictly avoided with a personal history of deep vein thrombosis or pulmonary embolism.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, there was an increased risk of venous thromboembolic events. In the trial directly comparing tamoxifen with raloxifene in postmenopausal high-risk women, there was no significant difference in the risk of invasive breast cancer, but tamoxifen significantly reduced noninvasive breast cancer.
Label source:
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Severe Liver Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene is metabolized by the liver, and its use in individuals with severe liver impairment can lead to drug accumulation and potential toxicity.
Actionable advice:
This should be strictly avoided with severe liver disease.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Liver Disease. Clomiphene citrate therapy is contraindicated in patients with liver disease or a history of liver dysfunction
Label source:
FDA label: Clomiphene Citrate (Clomid) [class-derived from: clomiphene]
Action type:
avoid
Target id:
/class/serms
Target name:
Other SERMs (e.g., Tamoxifen, Raloxifene)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining multiple SERMs leads to unpredictable effects on estrogen receptors and offers no additional benefit, while potentially increasing risks.
Actionable advice:
This should not be combined with other selective estrogen receptor modulators.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In this study, the benefits of tamoxifen appeared to be independent of estrogen receptor status.
Label source:
Action type:
avoid
Target id:
/class/aromatase-inhibitors
Target name:
Aromatase Inhibitors (e.g., Anastrozole)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining enclomiphene (which increases testosterone) with an aromatase inhibitor (which blocks estrogen conversion) can lead to excessively low estrogen levels, causing significant side effects.
Actionable advice:
Co-administration should be avoided unless under strict medical supervision for a specific purpose.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol.
Label source:
Action type:
avoid
Target id:
/intervention/testosterone
Target name:
Exogenous Testosterone Therapy
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene works by stimulating your body's own testosterone production; taking external testosterone suppresses this natural process, making enclomiphene ineffective.
Actionable advice:
Enclomiphene should not be used while on testosterone replacement therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Do not apply testosterone topical solution USP to other parts of the body including to the scrotum, penis, abdomen, shoulders or upper arms.
Label source:
Action type:
avoid
Target id:
/biomarker/comprehensive-sex-hormone-panel
Target name:
Hormone Panel (T, E2, LH, FSH, SHBG)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Regular monitoring of sex hormones is essential to confirm the drug is working as intended and to ensure levels remain within a safe and optimal range.
Actionable advice:
Obtain a baseline hormone panel before starting and monitor periodically during treatment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option.
Label source:
Action type:
monitor
Target id:
/biomarker/comprehensive-liver-function-panel
Target name:
Liver Function Panel (AST, ALT)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As enclomiphene is processed by the liver, monitoring liver enzymes is a necessary precaution to ensure hepatic safety during treatment.
Actionable advice:
It is a good idea to check liver function before starting and periodically thereafter.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
The extent of enclomiphene metabolism was correlated with the amount of CYP2D6 present (p<0.001, Pearson correlation test). The findings indicate that CYP2D6 is primarily responsible for the metabolism of enclomiphene.
Label source:
Action type:
monitor
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel (Cholesterol, Triglycerides)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SERMs can influence cholesterol and triglyceride levels, making it important to monitor your lipid profile during therapy.
Actionable advice:
A lipid panel should be monitored at baseline and during treatment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The TG/HDL ratio was inversely associated with testosterone and SHBG levels in middle-aged and elderly Korean men.
Label source:
Action type:
monitor
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is a theoretical increased risk of blood clots with SERMs, which could counteract the effects of blood-thinning medications. This combination requires caution.
Actionable advice:
This is best used with caution, and it is important to discuss it with a doctor when taking any blood-thinning medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
This is because COUMADIN is a blood thinner medicine that lowers the chance of blood clots forming in your body.
Label source:
Action type:
informational_none
Target id:
/circadian/consistent-time
Target name:
Consistent Daily Timing
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking enclomiphene at the same time each day helps maintain stable blood concentrations, leading to more consistent hormonal effects.
Actionable advice:
A dose is best taken at the same time every day.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These data confirm the existence of a gonadal diurnal cycle for testosterone, which is probably controlled by the hypophysis, although a close correlation between the cyclicity of gonadotropins and testosterone secretion is not clearly demonstrated.
Label source:
Action type:
informational_none
Target id:
/biomarker/lh
Target name:
Luteinizing Hormone (LH) Test
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene is designed to increase LH levels. Testing while on the drug reflects its therapeutic effect, not your baseline, untreated state.
Actionable advice:
Understand that LH levels will be elevated on this therapy; this is the intended effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option.
Label source:
Action type:
monitor
Target id:
/biomarker/fsh
Target name:
Follicle-Stimulating Hormone (FSH) Test
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene is designed to increase FSH levels. Testing while on the drug reflects its therapeutic effect, not your baseline, untreated state.
Actionable advice:
Understand that FSH levels will be elevated on this therapy; this is the intended effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option.
Label source:
Action type:
monitor
Target id:
/biomarker/total-testosterone
Target name:
Total Testosterone Test
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene is designed to increase testosterone levels. Testing while on the drug reflects its therapeutic effect, not your baseline, untreated state.
Actionable advice:
Understand that testosterone levels will be elevated on this therapy; this is the intended effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option.
Label source:
Action type:
monitor
Target id:
/biomarker/estradiol
Target name:
Estradiol Test
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By increasing testosterone, enclomiphene also indirectly increases estradiol through aromatization. Testing while on the drug reflects this expected metabolic conversion.
Actionable advice:
Understand that estradiol levels will likely be elevated on this therapy; this is an expected effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because testosterone can be metabolized to estradiol by the aromatase enzyme, there has been controversy as to which gonadal sex steroid has the greater skeletal effect.
Label source:
Action type:
monitor
Target id:
/circadian/wake
Target name:
Morning (Upon Waking)
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
1
Description:
Taking enclomiphene in the morning may help align with the body's natural diurnal rhythm of testosterone production, which is highest upon waking.
Actionable advice:
Consider taking your daily dose within an hour of waking up.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Diurnal variations of serum sex hormone binding globulin (SHBG), testosterone (T) and estradiol (E2) in five normal adult men and five normal adult women were investigated. SHBG binding capacity was measured by both polyacrylamide gel electrophoresis and dextran-coated charcoal technique (DCC); T and E2 were assayed by RIA and free T and free E2 were determined by means of equilibrium dialysis. In male subjects the variations of SHBG binding capacity was associated with the changes of total T, free T and T/SHBG index, which had the highest concentrations in the morning and the lowest levels in the evening during the 24 h test period, but percentage free T remained unchanged.
Label source:
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Enclomiphene absorption is not significantly affected by food. Taking it with a meal can improve tolerability and reduce the chance of gastrointestinal upset.
Actionable advice:
May be taken with or without food; take with a meal if you experience stomach upset.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
While adverse effects of enclomiphene have not been directly studied, enclomiphene appears to be well tolerated with few adverse effects. Of the phase II/III trials of enclomiphene citrate, the reported side effects have included elevated estradiol levels, headache and abdominal discomfort.
Label source:
Action type:
informational_none
Target id:
/dietary/soy-products
Target name:
High-Dose Phytoestrogen Supplements
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High concentrations of phytoestrogens (e.g., from soy isoflavone or red clover supplements) could theoretically compete with enclomiphene for estrogen receptor binding, potentially reducing its effectiveness.
Actionable advice:
High-dose phytoestrogen supplements are generally best avoided while taking enclomiphene.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERβ compared to ERα has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-κB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system.
Label source:
Action type:
avoid
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While not specifically studied, grapefruit is a potent inhibitor of metabolic enzymes (CYP3A4) that could potentially alter enclomiphene levels, increasing the risk of side effects.
Actionable advice:
As a precaution, it is best to avoid grapefruit and its juice.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Attention to the induction or inhibition of cytochrome P450 by food content could help mitigate the risk of unwanted side effects.
Label source:
PubMed: Interactions Among Drugs, Food, Beverages, Alcohol, Herbs, Phytochemicals, Nutraceuticals, and Micronutrients: A Current and Updated Review. (PMID 42136239)
Action type:
avoid
Target id:
/biomarker/complete-blood-count
Target name:
Complete Blood Count (CBC)
Severity:
minor
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Monitoring red blood cell counts (hematocrit) is prudent, as significant increases in testosterone can sometimes stimulate red blood cell production.
Actionable advice:
Consider checking a CBC, including hematocrit, at baseline and after several months of therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis.
Label source:
Action type:
monitor
Target id:
/condition/hormone-sensitive-cancer
Target name:
Estrogen-Dependent Tumors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
As a modulator of estrogen receptors, enclomiphene should not be used in individuals with a history of estrogen-dependent cancers.
Actionable advice:
This should be strictly avoided with a history of hormone-sensitive cancers.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Class precaution: enclomiphene is an estrogen-receptor modulator/antagonist that alters the hormonal milieu, so it is avoided in estrogen-dependent malignancies absent specific evidence of safety. Class-level caution.
Label source:
Class inference
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0