Clomiphene Side Effects

Not all side effects for clomiphene may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to clomiphene: oral tablet

In addition to its needed effects, some unwanted effects may be caused by clomiphene. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking clomiphene:

More common
  • Bloating
  • stomach or pelvic pain

If any of the following side effects occur while taking clomiphene, check with your doctor or nurse as soon as possible:

Less common or rare
  • Blurred vision
  • decreased or double vision or other vision problems
  • seeing flashes of light
  • sensitivity of eyes to light
  • yellow eyes or skin

Some of the side effects that can occur with clomiphene may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Hot flashes
Less common or rare
  • Breast discomfort
  • dizziness or lightheadedness
  • headache
  • heavy menstrual periods or bleeding between periods
  • mental depression
  • nausea or vomiting
  • nervousness
  • restlessness
  • tiredness
  • trouble in sleeping

For Healthcare Professionals

Applies to clomiphene: compounding powder, oral tablet

General

At recommended dosages, clomiphene is generally well tolerated. Adverse reactions usually are mild, transient, and resolve when clomiphene is discontinued.[Ref]

Genitourinary

Male sterility after high dose therapy may be due to hyalinization of the tubular membranes and damage to the spermatids. In general, clomiphene enhances spermatozoal motility and does not change the sperm to abnormal or immature forms.[Ref]

Very common (10% or more): Ovarian enlargement, ovarian hyperstimulation syndrome
Common (1% to 10%): Abnormal uterine bleeding (intermenstrual spotting, menorrhagia), multiple pregnancies, spontaneous abortions (ectopic pregnancies, hydatiform moles, fetus papyraceous)
Uncommon (0.1% to 1%): Stillbirths, increased urinary frequency/volume, vaginal dryness, priapism
Frequency not reported: Temporary sterility in males
Postmarketing reports: Endometriosis, ovarian cyst, ovarian hemorrhage, tubal pregnancy, uterine hemorrhage[Ref]

Ocular

Common (1% to 10%): Blurred vision, lights, floaters, waves, unspecified visual complaints, photophobia, diplopia, scotomata, phosphenes
Frequency not reported: Scintillations, heat waves, irreversible palinopsia (prolonged afterimages), shimmering of the peripheral field
Postmarketing reports: Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis, photopsia, posterior vitreous detachment, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, temporary or prolonged loss of vision, possibly irreversible[Ref]

Cardiovascular

Very common (10% or more): Vasomotor flushes
Postmarketing reports: Arrhythmias, chest pain, edema, hypertension, palpitations, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitis.[Ref]

Endocrine

Frequency not reported: Gynecomastia, thyroid disorders
Postmarketing reports: Thyroid disorders[Ref]

Oncologic

Uncommon (0.1% to 1%): Leydig cell tumor of testis (in male treated for oligospermia)
Frequency not reported: Ovarian cancer, increased risk of borderline or invasive ovarian tumor
Postmarketing reports: Hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma, fibrocystic disease, breast carcinoma, endometrial carcinoma, astrocytoma, pituitary tumor, prolactinoma, neurofibromatosis, glioblastoma multiforme, brain abscess, luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma, hydatiform mole, choriocarcinoma, melanoma, myeloma, perianal cysts, renal cell carcinoma, Hodgkin's lymphoma, tongue carcinoma, bladder carcinoma[Ref]

Nervous system

Common (1% to 10%): Headache
Uncommon (0.1% to 1%): Dizziness, insomnia, light-headedness, nervous tension, vertigo
Postmarketing reports: Migraine headache, paresthesia, seizure, stroke, syncope[Ref]

Dermatologic

Uncommon (0.1% to 1%): Dermatitis, rash, hair loss, dry hair
Frequency not reported: Reversible alopecia, urticaria, acne, erythema nodosum, erythema multiforme
Postmarketing reports: Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritis, urticaria[Ref]

Gastrointestinal

Common (1% to 10%): Abdominal-pelvic discomfort/distention/bloating, nausea, vomiting
Uncommon (0.1% to 1%): Acute abdomen, constipation, diarrhea[Ref]

Hematologic

Uncommon (0.1% to 1%): Deep vein thrombosis
Frequency not reported: Pituitary hemorrhage (with undiagnosed pituitary tumor)
Postmarketing reports: Leukocytosis[Ref]

A 32-year-old woman receiving clomiphene citrate treatment for ovulation induction was admitted for complaints of swelling and pain in her right calf. Her medical history was unremarkable except for complications following an appendectomy three years prior which resulted in a deep vein thrombosis (DVT) and subsequent pulmonary embolism. The patient had been taking clomiphene two days prior to the development of the first DVT. Six months later, the treatment with clomiphene was renewed. The patient developed recurrent DVT following repeated standard clomiphene treatment.[Ref]

Hepatic

Postmarketing reports: Increased transaminases, hepatitis[Ref]

Metabolic

Uncommon (0.1% to 1%): Increased appetite, weight gain/loss

Musculoskeletal

Postmarketing reports: Arthralgia, back pain, myalgia[Ref]

Other

Common (1% to 10%): Breast discomfort
Uncommon (0.1% to 1%): Fatigue
Frequency not reported: Elevated levels of desmosterol (for prolonged therapy)
Postmarketing reports: Fever, tinnitus, weakness

Fetal/Neonatal Anomalies and Mortality:
Uncommon (0.1% to 1%): Congenital heart lesions, down syndrome, club foot, congenital gut lesions, hypospadias, microcephaly, harelip and cleft palate, congenital hip, hemangioma, undescended testicles, polydactyly, conjoined twins and teratomatous malformation, patent ductus arteriosus, amaurosis, arteriovenous fistula, inguinal hernia, umbilical hernia, syndactyly, pectus excavatum, myopathy, dermoid cyst of scalp, omphalocele, spina bifida occulta, ichthyosis, and persistent lingual frenulum, neonatal death, fetal death/stillbirth
Postmarketing reports: Skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot (clubfoot), spine, joints; septal heart defects, muscular ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, coarctation of the aorta; down syndrome; ear abnormalities and deafness; cleft lip and palate, imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, omphalocele; hypospadias, cloacal exstrophy, lung tissue malformations; malformations of the eye and lens (cataract); neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic leukemia; neural tube defects (anencephaly, meningomyelocele), microcephaly, hydrocephalus; renal agenesis and renal dysgenesis; dwarfism, mental retardation

Psychiatric

Uncommon (0.1% to 1%): Depression
Postmarketing reports: Anxiety, irritability, mood changes, psychosis[Ref]

Respiratory

Uncommon (0.1% to 1%): Pulmonary embolism (in male treated for infertility)[Ref]

References

1. "Product Information. Clomid (clomiphene)." Hoechst Marion-Roussel Inc, Kansas City, MO.

2. Check JH, Murdock MG, Caro JF, Hermel MB "Case report: cystic gynecomastia in a male treated with clomiphene citrate." Fertil Steril 30 (1978): 713-5

3. Morgan H, Paredes RA, Lachelin GC "Severe ovarian hyperstimulation after clomiphene citrate in a hypothyroid patient. Case report." Br J Obstet Gynaecol 90 (1983): 977-82

4. Gabos P "Clomiphene citrate therapy and associated ovarian endometrial cysts." Obstet Gynecol 53 (1979): 763-5

5. Mor-Joseph S, Anteby SO, Granat M, Brzezinsky A, Evron S "Recurrent molar pregnancies associated with clomiphene citrate and human gonadotropins." Am J Obstet Gynecol 151 (1985): 1085-6

6. Chow KK, Choo HT "Ovarian hyperstimulation syndrome with clomiphene citrate. Case report." Br J Obstet Gynaecol 91 (1984): 1051-2

7. Bjork JT, Varma RR, Borkowf HI "Clomiphene citrate therapy in a patient with Laennec's cirrhosis." Gastroenterology 72 (1977): 1308-11

8. Thorneycroft IH "Current status of ovulation induction with clomiphene citrate." Fertil Steril 41 (1984): 806-8

9. Patty JR, Galle PC, McRae MA "Massive ovarian edema in a woman receiving clomiphene citrate. A case report." J Reprod Med 38 (1993): 475-9

10. Ben-Shlomo I, Zohar S "Quadruplets following cessation of clomiphene citrate. A case of sustained effect." Acta Obstet Gynecol Scand 68 (1989): 379-80

11. Holtz G, Kling OR, Miller DD, Wilson DA "Ovarian hyperstimulation syndrome caused by clomiphene citrate." South Med J 75 (1982): 368-9

12. Shimono J, Tsuji H, Azuma K, Hashiguchi M, Fujishima M "A rare case of hepatic injury associated with ovarian hyperstimulation syndrome." Am J Gastroenterol 93 (1998): 123-4

13. Landefeld CS, Schambelan M, Kaplan SL, Embury SH "Clomiphene-responsive hypogonadism in sickle cell anemia." Ann Intern Med 99 (1983): 480-3

14. Lawton AW "Optic neuropathy associated with clomiphene citrate therapy." Fertil Steril 61 (1994): 390-1

15. Rock T, Dinar Y, Romem M "Retinal periphlebitis after hormonal treatment." Ann Ophthalmol 21 (1989): 75-6

16. Purvin VA "Visual disturbance secondary to clomiphene citrate." Arch Ophthalmol 113 (1995): 482-4

17. Roch LM 2d, Gordon DL, Barr AB, Paulsen CA "Visual changes associated with clomiphene citrate therapy." Arch Ophthalmol 77 (1967): 14-7

18. Benshushan A, Shushan A, Paltiel O, Mordel N, Laufer N "Ovulation induction with clomiphene citrate complicated by deep vein thrombosis." Eur J Obstet Gynecol Reprod Biol 62 (1995): 261-2

19. Inbar OJ, Levran D, Mashiach S, Dor J "Ischemic stroke due to induction of ovulation with clomiphene citrate and menotropins without evidence of ovarian hyperstimulation syndrome." Fertil Steril 62 (1994): 1075-6

20. Walker AB, Eldridge PR, Macfarlane IA "Clomiphene-induced pituitary apoplexy in a patient with acromegaly." Postgrad Med J 72 (1996): 172-3

21. Bujan L, Mieusset R, De Zong Z, Mansat A, Pontonnier F "Development of Leydig cell tumour in association with clomiphene treatment for oligozoospermia." Br J Urol 69 (1992): 659-60

22. Bolton PM "Bilateral breast cancer associated with clomiphene." Lancet 2 (1977): 1176

23. Potashnik G, Lerner-Geva L, Genkin L, Chetrit A, Lunenfeld E, Porath A "Fertility drugs and the risk of breast and ovarian cancers: results of a long-term follow-up study." Fertil Steril 71 (1999): 853-9

24. Fuller PN "Malignant melanoma of the ovary and exposure to clomiphene citrate: a case report and review of the literature." Am J Obstet Gynecol 180 (1999): 1499-503

25. Melamed I, Bujanover Y, Hammer J, Spirer Z "Hepatoblastoma in an infant born to a mother after hormonal treatment for sterility." N Engl J Med 307 (1982): 820

26. Hull ME, Kriner M, Schneider E, Maiman M "Ovarian cancer after successful ovulation induction: a case report." J Reprod Med 41 (1996): 52-4

27. Neoptolemos JP, Locke TJ, Fossard DP "Testicular tumour associated with hormonal treatment for oligospermia." Lancet 2 (1981): 754

28. Haskell CM, Herrmann C Jr, Marsh GG "Clomiphene-induced neurological dysfunction." Lancet 2 (1977): 1227

29. Nilsson A, Nilsson S "Testicular germ cell tumors after clomiphene therapy for subfertility." J Urol 134 (1985): 560-2

30. Carrasco D, Barrachina M, Prieto M, Berenguer J "Clomiphene citrate and liver-cell adenoma." N Engl J Med 310 (1984): 1120-1

31. Rimmington MR, Vine SJ, Chui DK, Walker SM "Convulsions after clomiphene citrate." BMJ 309 (1994): 512

32. Cashman FE, Sheppard R "Clomiphene citrate as a possible cause of psychosis." Can Med Assoc J 126 (1982): 118

33. Oyffe I, Lerner A, Isaacs G, Harel Y, Sigal M "Clomiphene-induced psychosis [letter]." Am J Psychiatry 154 (1997): 1169-70

34. Chamberlain RA, Cumming DC "Pulmonary embolism during clomiphene therapy for infertility in a male: a case report." Int J Fertil 31 (1986): 198-9

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