Gonadotropin-Releasing Hormone Analogs - A Walkthrough

Introduction:

The pituitary gland in the endocrine system utilizes gonadotropin-releasing hormone (GnRH) to stimulate the manufacturing of luteinizing hormone and follicle-stimulating hormone. These hormones produce the sex hormones estrogen, testosterone, and progesterone. GnRH is important for fertility, sex drive, and sexual maturity. GnRH analogs act by interfering with the effect of gonadotropin-releasing hormone on the pituitary gland present in the brain. These medications are administered in the form of nasal spray or injection since these are inactive when taken orally.

How Is Gonadotropin-Releasing Hormone Otherwise Known As?

Gonadotropin-releasing hormone is otherwise known as:

• GnRH.

• Luliberin.

• Luteinizing hormone-releasing hormone (LHRH).

What Are GnRH Analogs and How Do They Work?

A GnRH analog is a medication that prevents the release of estrogen from the ovaries and results in temporary and reversible menopause. GnRH analogs mimic the gonadotropin-releasing hormone produced in the body. Since GnRH governs the production of female reproductive hormones, namely estrogen and progesterone, administering GnRH analog will temporarily stop ovarian activity. This, in turn, turns off the production of hormones and menstruation for the duration of treatment.

GnRH analogs are used in:

• GnRH analogs are used in the process of ovulation induction since they facilitate a better and more predictable response to medications used for treating ovulation disorders in women and for in-vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) cycles. Pregnancy rates associated with GnRH analogs are usually high, and there are minimal ‘canceled cycles’ pertaining to unsatisfactory response of the ovaries.

• Suppose GnRH analogs are employed in the treatment of uterine fibroids (non-cancerous or benign growths in the uterus) and endometriosis (the growth of tissue similar to the lining of the uterus in other parts of the body). In that case, GnRH analog suppression may have fewer side effects when compared to other medications like Danazol and can increase the chances of pregnancy right after stopping the treatment.

• GnRH analog suppression prior to surgery for these issues can help minimize blood loss, decrease scar formation or adhesion, and maximize successful outcomes for future pregnancy.

What Are the Commonly Used GnRH Analogs in Gynecology?

The commonly used GnRH analogs are as follows:

• Lupron was the first medication that was used and has been in use since 1986. It is administered as a small daily subcutaneous (given under the skin) injection or can be given as a long-acting intramuscular (IM) injection.

• The newest form of GnRH analog called Synarel, which was introduced in the early 1990s, is usually given as a twice-daily nasal spray.

Both the above-mentioned drugs have similar mechanisms of action but vary in the mode of delivery and length of effect.

For What Gynecological Conditions Are GnRH Analogs Used?

GnRH analogs are used for the following gynecological conditions:

• Premenstrual Syndrome: Premenstrual syndrome is linked with a woman’s menstrual cycle wherein a woman experiences a blend of physical and psychological symptoms, which can have a serious impact on her life. Usually, a three-month trial with GnRH analogs is done to investigate the condition. If the symptoms improve upon the use of GnRH analogs, then further decisions are made based on this response. If symptoms persist, then further treatment to remove the ovaries will not be recommended.

• Endometriosis or Adenomyosis: The growth of tissue in other parts of the body similar to the lining of the uterus is called endometriosis. Since this condition is based on the sensitivity of the hormones, temporarily shutting down the hormone production from the ovary can aid in identifying the condition and provide a period of relief before a more definitive treatment, like the removal of ovaries. If symptoms persist despite shutting down the activity of the ovaries, then removal of ovaries will not provide the needed solution.

• Fibroids: Fibroids are non-cancerous (benign) swellings that originate from the muscular layer of the uterus and can cause painful and heavy periods. These muscular swellings are sensitive to hormones, and treating these with GnRH analogs can shrink the swellings temporarily, which can help improve the symptoms for a while and may aid with planned surgery to remove them.

• Chronic Pelvic Pain: A trial with GnRH analogs can be done as a diagnostic test to identify if the chronic pelvic pain is due to gynecological or non-gynecological causes. If the symptoms improve upon the use of GnRH analogs, then further treatment decisions, like whether surgery is to be done or not, can be decided.

Do GnRH Analogs Have a Contraceptive Effect?

GnRH analogs do not offer contraception. Hence, it is necessary that one follows a reliable contraceptive method while on GnRH analogs. Also, one must not be pregnant during the start of the treatment. A urine pregnancy test will be done. If the result is positive or if there are any possible chances of pregnancy, then the GnRH analog will not be administered. GnRH analogs are not licensed to be used as contraception. Hence, individuals should take precautionary measures and use a barrier method of contraception during the course of the treatment.

How Are GnRH Analogs Administered, and What Is the Treatment Duration?

GnRH analogs are usually injected subcutaneously (administered under the skin) into the abdominal wall. These analogs are administered every four weeks or every three months as an outpatient procedure by a physician or a nurse. Certain preparations are available as a nasal spray and can be self-administered.

GnRH analogs are licensed to be used for a duration of six months. If needed, continuing this medication beyond six months has to be decided by the treating physician. However, treatment using GnRH analogs beyond six months may require hormone replacement therapy (HRT) in addition to prevent bone thinning, which can occur as a result of prolonged use of GnRH analogs.

At times, the physician may start HRT earlier than six months or at the beginning of the use of GnRH analogs. Apart from prevention of bone thinning, HRT also has the ability to minimize menopausal symptoms associated with GnRH analogs. The HRT does not elevate the risk of breast cancer since it will be a replacement of the hormones that are normally manufactured by the ovaries.

Are There Any Side Effects Associated With GnRH Analogs?

GnRH analogs may result in temporary symptoms of menopause in a few women like:

• Headaches.

• Hot flashes.

• Vaginal dryness.

• Decrease in breast size.

• Nausea.

• Mood changes.

• Acne.

• Dizziness.

• Muscle pains.

During the first few days, a few women may experience breast tenderness, fluid retention, and other symptoms that may mimic the onset of a period. These symptoms are usually mild and are not bothersome. Though rare, there may be itching, swelling, temporary burning, skin discoloration, or soreness at the site of injection, following the administration of Lupron. However, the effects of GnRH analogs on the ovaries return to normal when the medications are discontinued. There are neither any reports of any serious complications from the use of these medications nor any reported adverse effects on pregnancy or the future child.

Conclusion

Gonadotropin-releasing hormone (GnRH) analogs are medications that minimize the manufacture of hormones like estrogen and progesterone by the ovaries. The menopause effect produced by the GnRH analog is temporary and reversible. Once the medication is discontinued, menstruation usually occurs after six to 10 weeks, and there are no long-term effects on the fertility of the patient. GnRH analogs are generally used in IVF and GIFT cycles to enhance the quality and number of eggs available for fertilization.