Clomid® (Clomiphene): Eye Side Effects – Hallucinations –

Clomid® (clomiphene citrate, CC) is an oral ovulation-inducing drug.
First described in 1961,¹and for more than 50 years since, it has been used safely and widely as a fertility treatment.

Clomid® suppresses the action of the female hormone estrogen.
It acts on the pituitary gland in the brain and promotes the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Actions of estrogen:
This hormone plays an important role in female reproductive function (growth of the uterine lining, development of the mammary glands, and so on) and in metabolism and health maintenance (maintaining bone mass, lipid metabolism, and so on).
Its secretion rises from puberty, peaks in the 20s and 30s, and declines toward menopause, so its decline raises the risk of osteoporosis, dyslipidemia, and other conditions.

Although it is a drug used in gynecology, it is sometimes used in men as well.

Because it also has a muscle-building effect,WADA（World Anti-Doping Agency）it is also known to be listed on the World Anti-Doping Code Prohibited List.

Drug names:
Clomid® (Shionogi → Fuji Pharma)
Serophene® (Merck Biopharma)
Femilon® (Fuji Pharma), and others
Clomid® (Clomiphene): Eye Side Effects – Hallucinations –

Clomid® (Clomiphene): Eye Side Effects – Hallucinations –

“Seeing afterimages: palinopsia” (Palinopsia）

“Seeing afterimages: palinopsia” (Palinopsia）is the problem in many cases^2,3。

✔ Eyes flicker
✔ Afterimages remain
✔ Glare
✔ Blurred vision
✔ Things appear to shake

Here are a few cases.

• A 30-year-old woman
Four days after starting 100 mg of clomiphene citrate (CC) by mouth,
she noticed visual abnormalities such as afterimages, seeing figures of people, seeing light when moving from a dark place to a bright one, and things looking wavy during the day.

The symptoms lasted about 5 to 10 minutes and eased after she finished taking it on day 5.

Eye examinations found no abnormalities.

When she later resumed CC, similar symptoms appeared.

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The two types of palinopsia – Hallucinatory / phantom / illusory

Palinopsia is classified into two types⁴。
* Please also see the Google Images results at the link.

○Hallucinatory palinopsias 　“Hallucination-like”
Due to effects on the back of the brain (posterior cortex),
the afterimage has a clear shape, lasts a long time, and is seen in high resolution

○Illusory palinopsias　“Phantom, illusory”
migraines, head trauma, prescription drugs, or hallucinogen persisting perception disorder.
the afterimages described are affected by ambient light and motion and are unformed, indistinct, or low resolution.

Migraine, after a blow to the head, hallucinogen persisting perception disorder (HPPD)
The afterimage looks as if seen in a hazy light, its shape is not clear, and it is seen in low resolution

Of these, in this woman,
the symptoms are considered to correspond to illusory palinopsia caused by clomiphene.

It has long been pointed out that changes in female hormones such as estrogen can affect vision.

It has been suggested that female hormones may influence the function of the nerves involved in vision through neurotransmitters, but the detailed mechanism has not yet been fully clarified.

Clomid® and the Eyes: Other Symptoms, and How Long Do the Effects Last?

It can also cause central retinal vein occlusion (CRVO, CRVO), a serious eye disease⁶。

The thrombus-forming action of estradiol, one of the estrogens, is thought to be the cause.

○ A 32-year-old woman, infertility, took CC for 10 months
Shimmering, afterimages, sensitivity to light: symptoms lasted for2.5 years

○ A 32-year-old woman, infertility, took CC for 4 months
Vibrating, shimmering, flickering, afterimages, sensitivity to light: symptoms lasted for4 years

○ A 36-year-old woman, infertility, took CC for more than 10 months
Blurred vision, flickering, sensitivity to light: the symptoms worsened and lasted7 years

○ A 36-year-old woman, infertility, took CC for 8 months　
CRVO (central retinal vein occlusion):After 5 monthsthe symptoms improved

○ A 35-year-old man, infertility, took CC for 8 months
CRVO (central retinal vein occlusion):After 7 monthsthe symptoms improved

○ A 38-year-old woman, infertility, took CC for 1 month
Some reports also state that there are few eye side effects.⁷。

Maculopathy, uveitis, optic neuropathy

Besides CRVO, other serious side effects have also been described.

○ Maculopathy⁸　
○ Anterior uveitis⁹　
○ Optic neuropathy¹⁰

If you take Clomid® (clomiphene) and have concerns, please see an eye doctor.

(References)

1. Greenblatt, R.B., Barfield, W.E., Jungck, E.C., Ray, A.W., 1961. Induction of Ovulation with MRL/41: Preliminary Report. JAMA 178, 101–104. https://doi.org/10.1001/jama.1961.03040410001001
2. Purvin, V.A., 1995. Visual Disturbance Secondary to Clomiphene Citrate. Arch Ophthalmol 113, 482–484. https://doi.org/10.1001/archopht.1995.01100040102034
3. Venkatesh, R., Gujral, G.S., Gurav, P., Tibrewal, S., Mathur, U., 2017. Clomiphene citrate-induced visual hallucinations: a case report. J Med Case Reports 11, 60. https://doi.org/10.1186/s13256-017-1228-0
4. Gersztenkorn, D., Lee, A.G., 2015. Palinopsia revamped: a systematic review of the literature. Surv Ophthalmol 60, 1–35. https://doi.org/10.1016/j.survophthal.2014.06.003
5. Nicoletti, F., Patti, F., Ferrara, N., Canonico, P.L., Giammona, G., Condorelli, D.F., Scapagnini, U., 1982. Comparative effects of estrogens and prolactin on nigral and striatal GAD activity. Brain Research 232, 238–241. https://doi.org/10.1016/0006-8993(82)90633-3
6. Viola, M.I., Meyer, D., Kruger, T., 2011. Association between Clomiphene Citrate and Visual Disturbances with Special Emphasis on Central Retinal Vein Occlusion: A Review. Gynecol Obstet Invest 71, 73–76. https://doi.org/10.1159/000319497
7. Racette, L., Casson, P.R., Claman, P., Zackon, D.H., Casson, E.J., 2010. An investigation of the visual disturbances experienced by patients on clomiphene citrate. Fertility and Sterility 93, 1169–1172. https://doi.org/10.1016/j.fertnstert.2008.11.025
8. Tunc, M., 2014. Maculopathy following extended usage of Clomiphene citrate. Eye 28, 1144–1146. https://doi.org/10.1038/eye.2014.121
9. Myers, T.D., Fraunfelder, F.W., 2008. Bilateral anterior uveitis associated with clomiphene citrate. Ocul. Immunol. Inflamm. 16, 23–24. https://doi.org/10.1080/09273940701799155
10. Lawton, A.W., 1994. Optic neuropathy associated with clomiphene citrate therapy. Fertility and Sterility 61, 390–391. https://doi.org/10.1016/S0015-0282(16)56537-6