The Oestrogen Dependent Condition Of Endometriosis Biology Essay

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Endometriosis is a condition an oestrogen-dependent condition in which endometrial cells that are normally found growing outside of the uterus. The endometrial cells are shed every month during menstruation, and so endometriosis is most likely to affect women during their childbearing years. Although there are not always symptoms, it can be painful and lead to other problems. The endometrial lining of the uterus thickens each month to prepare for an egg. It is here where an egg cell implants and grows if it is fertilized. If an egg is not fertilized, the endometrial breaks down and exits the body during the menstrual period. Endometriosis affects women who are between 20-35 years.(Howard, 2009) Endometriosis is present in 10 percent plus of premenopausal women and 2-5 percent of post menopausal women. It also found in all ethnic groups.(refef).

Epidemiology

Endometriosis is characterized by the presence of ectopic endometrial tissue but the pathogenesis of ectopic lesions cannot be satisfactorily explained (Huang, 2008) (refef). Endometriosis has well known associations with menopause both in terms of secondary outcomes from medical and surgical therapy in premenopausal women, as well as a natural occurrence/recurrence of the disease in women going through menopause naturally. In Palep-Singh and Gupta's review article (2009) they discussed the current day modalities of management of endometriosis with their pros and cons especially in the context of menopause and cancer

Endometrial cells implant outside of the uterus - usually on the ovaries, fallopian tubes, outer wall of the uterus, or intestines. However, these implants follow the same pattern as the endometrial lining the uterus of getting thicker, breaking down, and bleeding. Problems occur because these growths are outside of the uterus, and the blood cannot flow properly. This can lead to the formation of scar tissue and cysts as well as difficulties getting pregnant.

It is not know the exact causes of endometriosis, but there are several theories, many theories have been proposed, but no single theory can explain all aspects of endometriosis, suggesting that endometriosis is a heterogeneous disease. Researchers do know that the hormone oestrogen, which is at its highest levels during childbearing years, is likely to contribute to endometriosis. Other possible causes of endometriosis include:

Retrograde menstruation - when endometrial tissue is deposited in strange locations because of menstrual flow that backs up into the fallopian tubes and abdominal cavity. Ceolomic metaplasia - the areas lining the pelvic organs have certain cells that can grow into other forms of tissue such as endometrial cells. Surgery - endometrial tissues are directly transferred outside the uterus during episiotomy or Caesarean section. Blood and lymph systems - endometrial cells travel via the bloodstream or lymphatic system to distant places such as the brain and other places far from the pelvis. Immune system problems - cause the body to not recognize and destroy cells or tissue that is growing where it should not be.

Although most women with endometriosis do not have symptoms and symptoms vary from woman to woman, the following symptoms have been known to occur: The most common symptom of endometriosis is pelvic pain. The pain often correlates to the menstrual cycle, however a woman with endometriosis may also experience pain at other times during her monthly cycle (Lethaby et al., 2005).

For many women, but not everyone, the pain of endometriosis can unfortunately be so severe and debilitating that it impacts on her life significant ways. Symptoms of endometriosis include several types of severe pain and infertility, which significantly impair the quality of life in these women Pain may be felt before/during/after menstruation, during ovulation, in the bowel during menstruation, when passing urine, during or after sexual intercourse, in the lower back region (Howard, 2009). Other symptoms may include: diarrhoea or constipation (in particular in connection with menstruation), abdominal bloating (again, in connection with menstruation), heavy or irregular bleeding and fatigue. The other well known symptom associated with endometriosis is infertility. It is estimated that 30-40 percent of women with endometriosis are sub fertile. (Howard, 2009)

Endometriosis is often treated surgically upon diagnosis but with a higher rate of recurrence, suggesting that a combination of surgical and medical management might provide better outcomes. (Lethaby et al., 2000). The primary goal of medical treatment for endometriosis is to halt the growth and activity of endometriosis lesions. The most widely utilized medical treatment for endometriosis involves use of gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives. Conventional agents also include androgen derivates and progestin.

There are many ways to treat the symptoms of endometriosis but to treat the underlying disease often requires repeated medical or surgical interventions. Management of endometriosis is varied. Medical treatments for endometriosis include oral contraceptives, progestagens, testosterone derivatives, and gonadotropin-releasing hormone (GnRH) agonists. Surgical treatments include ablative techniques (destroying the endometriosis with energy such as laser or electricity) and excision (using scissors, electricity, or laser). This surgical approach aims to relieve symptoms whilst conserving reproductive function. More radical surgery in the form of hysterectomy, removal of the ovaries (oophorectomy), or both may also be performed. Conventional medical and surgical treatments for endometriosis aim to remove or decrease deposits of ectopic endometrial (tissue like the lining of the uterus but found outside the uterus). Non-steroidal anti-inflammatory drugs (NSAIDs) work by decreasing the amount of pain experienced by women. They do not remove or decrease the deposits of ectopic endometrial. NSAIDs may also act on local cytokines within the actual endometriosis deposits, as well as acting as analgesics. (Allen et al., 2009).

Gonadotrophin-releasing hormone (GnRH) analogues, danazol, progestogens and oestrogen-progestin combinations have all proven effective in relieving pain and reducing the extent of endometriotic implants. However, symptoms often recur after discontinuation of therapy and hypoestrogenism-related side effects limit the long-term use of most medications. Furthermore, these therapies are of limited value in patients with a desire to become pregnant because they inhibit ovulation. An important target for current research is to identify effective therapies that can be safely administered in the long term. GnRH analogues with add-back therapy, progestogens and continuous oral contraceptive are options available for a medium or long-term systemic treatment. Mifepristone, an antiprogestogen, may constitute an alternative if encouraging preliminary data on its effectiveness and tolerability are confirmed. A very appealing area of interest is the possibility of treating endometriosis without suppressing ovarian function. Aromatase inhibitors might have such characteristics as they have been shown to inhibit oestrogen production selectively in endometriosis lesions, without affecting ovarian function; the clinical role of these drugs in the treatment of endometriosis is under evaluation. Levonorgestrel medicated intrauterine device has proven effective in relieving dysmenorrhoea associated with endometriosis, as well as pain associated with rectovaginal endometriosis. Although a systemic absorption is present determining side effects, this approach is promising in the long-term management of this condition. A fundamental objective of research in endometriosis treatment is to develop new therapeutic approaches based on the findings from experimental studies on the aetiopathogenesis of the disease. (Cause and development of a disease or abnormal condition)(Allen et al., 2009)

Increasing knowledge about the pathogenesis of endometriosis at the cellular and molecular levels may give us the opportunity to use new, specific agents for treatment, including aromatase inhibitors, progesterone antagonists, selective progesterone receptor modulators, GnRH antagonists, intrauterine releasing systems with progestin and new pharmaceutical agents affecting inflammation, angiogenesis, and matrix metalloproteinase activity. The body normally makes GnRH in a small gland in the brain (the pituitary) and it is this hormone that stimulates the ovary to develop eggs and produce oestrogen, leading to the normal menstrual cycle. If GnRH agonist is given, it floods the system and confuses the delicately controlled balance, leading to a complete block of egg development, oestrogen production and menstrual cycle. It effectively makes one 'menopausal' for the time that use the treatment and without the oestrogen stimulation, endometriosis shrinks down and becomes inactive.

Prostaglandins, thromboxanes are referred to the eicosanoids which are the cyclooxygynase (COX) and lipooxygenase metabolites arachidonic acid (AA) . COX catalyses the biosynthesis of prostaglandin and thromboxane. (Lethaby et al., 2000)

Many of these promising new agents may prevent or inhibit the development of endometriosis. Further clinical trials may determine if these new therapies are superior to current medical treatment strategies for endometriosis. In this project we are using prostaglandins as treatment of endometriosis.

The aim of this project is to culture endometrial cells from consenting non-pregnant donors and evaluate the effects of different prostaglandin in the treatments on endometrim using sterile technique. Different prostaglandins used are, prostaglandin (PG) f2α, prostaglandin (PG) E2 and thromboxane. Also different concentrations will be used for these prostaglandins. Changes in viability will be assessed using light microscope with digital camera and by colorimetric redox reactions. Prostaglandins that will inhibit endometrial cell growth may be the potential treatments for endometriosis.

Objective & methodology: To evaluate treatment ectopic and eutopic endometrial stromal cells in vitro using prostaglandins at different concentrations. To find out which prostaglandin are the potential treatments for endometriosis those which will l inhibit endometrial cell growth.

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