What is the hormonal / medical therapy for endometriosis?

The basic approach in hormonal treatments for endometriosis is to block production of female hormones (estrogen and progesterone) or to prevent ovulation with other hormonal effects.

Specific hormonal agents may have different effects for women with endometriosis.

• Inducing Pseudopregnancy:
  
  Oral contraceptives that contain estrogen and progestins mimic a pregnant state and block ovulation. (Progestins are natural or synthetic forms of progesterone).
  
  Progestins may also be used alone, since they have specific effects that can cause the endometrial tissue itself to atrophy.
  
  
• Inducing Pseudomenopause:
  
  Gonadotropin-releasing hormone (GnRH) agonists or gestrinone, an anti-progesterone that mimic menopause. They reduce estrogen and progesterone to their lowest level.
  
  
• Inducing On-going Blockage of Ovulation.
  
  Danazol, a derivative of male hormones, is a powerful ovulation blocker.

At this time, studies report that between 80% and 85% of women achieve pain relief after taking these agents. To date, comparison studies have found few differences in effectiveness among the major hormonal treatments. Differences occur mostly in their side effects.

Women should discuss the effects of particular medications with their physicians to determine the best choice.

Oral Contraceptives

Oral contraceptives (OCs), commonly known collectively as "the Pill", contain combinations of an estrogen and a progestin (either a natural progesterone or the synthetic form called progestogen).

OCs may reduce the risk of ovarian cancer by 30% to 50% and of endometrial cancer by 50%, which is a potentially mportant benefit in women with endometriosis. (Patch contraceptives are available, but they may increase the risk for menstrual cramping.)

When used throughout a menstrual cycle, they suppress the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevents ovulation.

There are many brands available. Women should discuss the best options for their individual situations with their physician.

Estrogen and progestin each cause different side effects. The most serious side effects are due to the estrogen in the combined pill. Uncommon but more dangerous complications of OCs include high blood pressure and deep-vein blood clots (thrombosis), which may contribute to heart attacks or strokes in rare cases.

Progestins

Progestins can prevent ovulation and reduce the risk for endometriosis in the following ways:

• They inhibit luteinizing hormone (LH), one of the reproductive hormones important in ovulation.
  
• They change the lining of the uterus and eventually cause it to atrophy.

Specific Progestins.

Medroxyprogesterone (Depo-Provera), which is administered by injection typically every three months, is the standard progestins used.

Other progestins that are showing benefits include norethisterone (Micronor, Noriday, Noristerat), dienogest, and lynestrenol.

Progestin-releasing intrauterine devices IUDs can be very helpful for many women with endometriosis, particularly an advanced version called the levonorgestrel-releasing intrauterine system, or LNG-IUS (Mirena). Studies are suggesting that the LNG-IUS reduces endometrial cell proliferation and increases cell self-destruction. Progestin released by the IUD mainly effects the uterus and cervix and so it causes fewer widespread side effects than the other forms of progestins do.

Side Effects of Progestins.
Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that only uses progestin, although they may be less or more severe depending on the form and dosage of the contraceptive. Side effects may include the following:

• Changes in uterine bleeding. Such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods. Be sure to check with the physician if any of these occur.
  
• Unexpected flow of breast milk. (Check with the physician if this occurs to be sure other abnormalities are not causing it.)
  
• Abdominal pain or cramps.
  
• Diarrhea.
  
• Fatigue, unusual tiredness, weakness.
  
• Hot flashes.
  
• Decreased sex drive.
  
• Nausea.
  
• Trouble sleeping.
  
• Depression, irritability, or other mood changes.
  
• Swelling in the face, ankles, or feet.
  
• Weight gain.

Newer formulations of combination pills that use low-dose estrogen and newer progestins may reduce and even avoid many of these side effects.

Progestins used in non-oral contraceptives, such as the LNG-IUS IUD, also may not pose as high a risk for these side effects.

If side effects persist or are severe, a woman should always talk to her physician. Many women do not experience these side effects, or if they do, their bodies eventually adjust.

GnRH Agonists

Gonadotropin releasing hormone (GnRH) agonists are effective hormone treatments for endometriosis. They are able to block the release of the reproductive hormones LH (luteinizing hormone) and FSH (follicular-stimulating hormone). As a result, the ovaries stop ovulating and no longer produce estrogen which is required for the growth of the endometriotic implants

Specific GnRH Agonists.

GnRH agonists include goserelin (Zoladex), buserelin, a monthly injection of leuprolide (depot Lupron), and a nasal spray, Nafarelin (Synarel).

Side Effects and Complications.

Commonly reported side effects (which can be severe in some women) include menopause-like symptoms that include hot flashes, night sweats, and dryness in the vagina, weight change, and. The possible osteoporosis. Women ordinarily should not take them for more than six months.

GnRH treatments used alone do not prevent pregnancy. Furthermore, if a woman becomes pregnant during their use, there is some risk for birth defects.

Women who are taking GnRH agonists should use non-hormonal birth control methods, such as the diaphragm, cervical cap, or condoms while on the treatments.

Danazol

Danazol is a synthetic substance that resembles a male hormone. It suppresses the pathway leading to ovulation.

A high drop-out rate occurs, most often because of adverse side effects, particularly male characteristics, such as growth of facial hair, acne, weight gain, and deepening of the voice. Danazol may increase the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have also been reported, as well as rare cases of liver damage.

Antiprogestins

Antiprogestins are promising agents for endometriosis because they reduce both estrogen and progesterone receptors.

These include

• Gestrinone.
  
• Mifepristone.

Investigative Hormones

GnRH Antagonists.

GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). These are newer agents differ from GnRH agonists in that they have a direct effect on the pituitary gland. The result is quicker action. They also pose a lower risk for complications and side effects.

Aromatase Inhibitors.

Drugs that inhibit aromatase, an enzyme that is a major source of estrogen in postmenopausal women are being studied for effects against endometriosis.

Selective Estrogen-Receptor Modulators (SERMs).

Drugs known as selective estrogen-receptor modulators (SERMs) are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. They have not been widely studied for endometriosis and warrant more research.

Fulvetrant.

Fulvetrant (Faslodex) blocks estrogen andis being studied for uterine fibroids and endometriosis.