Primary Medical Uses of Cyclofenil
Cyclofenil is a nonsteroidal selective estrogen receptor modulator (SERM) that gained attention in the 1970s for its ability to regulate reproductive processes. Its main purpose was to address hormonal imbalances contributing to female infertility and menstrual disorders. Specifically, it was prescribed for two key conditions related to fertility:
- Anovulatory Infertility: This condition involves a woman’s ovaries failing to release an egg during her menstrual cycle. Cyclofenil was used as an ovulation inducer to stimulate the process, particularly in women with normal estrogen and prolactin levels who had not responded to other treatments like clomiphene citrate.
- Menstrual Disturbances and Secondary Amenorrhea: It was also employed to treat irregularities in the menstrual cycle and secondary amenorrhea, which is the cessation of menstruation in a woman who has previously had periods.
How Cyclofenil Induces Ovulation
As a SERM, Cyclofenil exerts both estrogen-like (agonistic) and anti-estrogenic (antagonistic) effects depending on the tissue. In the context of fertility, its mechanism primarily involves the hypothalamic-pituitary-gonadal (HPG) axis. It works as a progonadotropin by blocking the actions of estrogen in the hypothalamus and pituitary gland. This anti-estrogenic effect disinhibits the release of gonadotropins, specifically:
- Follicle-Stimulating Hormone (FSH): FSH levels increase, stimulating the ovaries to produce and mature follicles.
- Luteinizing Hormone (LH): A subsequent LH surge triggers the final maturation and release of the egg, or ovulation.
This precise modulation is what allowed Cyclofenil to help restore normal ovulation in some patients.
Historical and Investigational Uses
Beyond its primary fertility applications, Cyclofenil was explored for other potential therapeutic uses, most of which showed limited or inconclusive results:
- Menopausal Hormone Therapy: Cyclofenil was used to treat menopausal symptoms in women, leveraging its estrogen-modulating properties.
- Lactation Suppression: In some cases, it was used to suppress lactation.
- Raynaud's Phenomenon and Scleroderma: Investigations were conducted in the 1980s to evaluate Cyclofenil's effectiveness in treating Raynaud's phenomenon, a condition causing reduced blood flow to the fingers and toes, and scleroderma, a connective tissue disease. However, a Cochrane review found insufficient evidence to support its use for these conditions.
Cyclofenil vs. Clomiphene
Cyclofenil is often compared to clomiphene citrate, another SERM used to induce ovulation. While both function similarly, there are notable differences that influenced their use:
| Feature | Cyclofenil | Clomiphene Citrate | Reference |
|---|---|---|---|
| Efficacy | Generally considered less effective than clomiphene, though some studies show comparable success in certain patient groups. | Considered more mainstream and often more effective for ovulation induction. | |
| Mechanism | Weaker SERM with a more nuanced effect on gonadotropins. | Stronger antiestrogenic effect at the hypothalamus. | |
| Side Effects | Potentially fewer side effects overall, but with a significant risk of liver toxicity and thromboembolic events. | More pronounced side effects such as visual disturbances, vasomotor symptoms (hot flushes), and ovarian cysts. | |
| Cervical Mucus | Thought to have a more favorable effect on cervical mucus, which can be negatively impacted by clomiphene. | Can have a detrimental drying effect on cervical mucus, potentially hindering sperm motility. |
Known Side Effects and Risks
The potential side effects of Cyclofenil were a major factor in its decline. The most concerning risk is hepatotoxicity, or liver damage. Biochemical signs of liver changes were observed in a significant portion of patients, and rare cases of overt hepatitis were reported, leading to the drug's withdrawal in some countries. Other side effects include:
- Gastrointestinal Issues: Nausea, vomiting, and abdominal discomfort were commonly reported.
- Neurological Symptoms: Some patients experienced headaches and dizziness.
- Visual Disturbances: There are case reports of serious visual issues, such as non-arteritic anterior ischemic optic neuropathy (NAION), particularly with higher than normal dosing.
- Thromboembolic Events: As with other SERMs, Cyclofenil can increase the risk of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE).
Cyclofenil is also contraindicated during pregnancy and in patients with severe liver disease or unexplained uterine bleeding.
Availability and Current Status
Cyclofenil was introduced in 1970 and marketed under various brand names, such as Ondogyne, Sexovid, and Fertodur. However, due to its side effect profile and the development of more effective and safer alternatives, it has been largely discontinued in most parts of the world. The drug may still be available in a few countries, including Brazil, Italy, and Japan. Furthermore, it has been banned as a doping agent by the World Anti-Doping Agency for its misuse by male athletes to increase testosterone levels. Given the availability of safer alternatives like clomiphene citrate, Cyclofenil's use has become rare in modern medicine.
Conclusion
What is the drug Cyclofenil used for? Historically, it served as a selective estrogen receptor modulator (SERM) for stimulating ovulation in women with anovulatory infertility and managing certain menstrual disturbances. While its mechanism offered a valuable tool for fertility treatment in its time, significant concerns regarding its safety profile, particularly liver toxicity and thromboembolic risks, led to its decline. The availability of more effective and safer alternatives like clomiphene citrate has rendered Cyclofenil largely obsolete in many regions, relegating its use primarily to historical and niche contexts where it may still be available. The drug's journey highlights the continuous evolution of pharmacology, where new agents with improved efficacy and safety profiles replace older treatments.
