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Hormonal influence in Endometriosis
                               Nicole Colón Carrión
                         Universidad de Puerto Rico, Cayey 1

       Endometriosis is one of the most common diseases present in women of reproductive
age. This paper aims to explain the influence of hormones in endometriosis development and
treatments. Several hormones, such as oestrigen, GnHR and GnH, are mentioned and studied.
Several Hormone treatments are used to reduce pain caused by endometriosis. This paper also
explains the effect of GnRH agonist in endometrial tissue.



      Endometriosis, also called Endo, is the     menstrual blood flows back through the
presence of endometrial tissue outside the        fallopian tubes and enters the pelvic or
uterine cavity. It is a condition where the       abdominal cavities instead of flowing out
endometrial tissue is misplaced and grows in
                                                  through the vagina. Another theory is that it
other places outside the uterus, such as the
pelvic and abdominal areas. These                 can be caused by Coelomic Metaplasia, a
endometrial tissues thicken and bleed during      process in which undifferentiated cells
a process called menstruation. When               develop into endometrial cells.
endometriosis occurs this tissue continues to     Endometriosis could be a hereditary disease;
bleed, accumulating blood outside the uterus      women with family history in endometriosis
and causing inflammation and pain. “It’s          could be more prone to develop this disease.
difficult to point out the exact percentage of
                                                  Some researchers are exploring the
patients that suffer from endometriosis; in
general, we speak of 10% of the female            possibilities of hormones being related to the
population of reproductive age” ( Vilalobos       development of endometriosis.
2009). Endometriosis can affect any
menstruating woman; it can appear at her                   Endometriosis can cause severe pain
first period until menopause or at the middle     in the abdominal and pelvic areas and
of her reproductive age. The exact cause of       infertility. “Endometriosis pain tends to get
endometriosis is still unknown.                   worst as time goes on, it can be mild,
                                                  modern or severe” (Mona, [unknown]). The
        “Because we don’t know why some           amount of pain that endometriosis can cause
women have endometriosis and others don’t,        is not proportional to the amount of tissue
we don’t know the cause of it” (Mona,             the body contains. Some women may
[unknown]). Even though the exact cause of        present severe pain having small quantity of
endometriosis is still unknown there are          tissue, while others present extensive
some theories that could explain the reason       endometriosis tissue and have little or no
for it. One of the theories is that               pain at all. Infertility is not a side effect that
endometriosis may be caused by Retrograde         all endometriosis patients will present but
Menstruation. Sampson postulates in 1920s         it’s said that about 30% of woman who
that endometriosis is caused by retrograde        suffer from endometriosis will have it. “The
menstruation; a process in which the
findings of physical examination can be as       a. Relationship with endometriosis
diverse as the symptom complex of the
history” (Rose,2005)                                  Growth hormone releasing hormone
                                              (GHRH) and GH hormone promote
                                              endometrial proliferation and may be
                                              involved in the pathogenesis of ovarian and
II. Hormones related to endometriosis         endometrial cancer such as endometriosis
                                              (Khorram et al. 2001; Schindler 2004;
                                              Slater et al. 2006). Slater (2006) concluded
   1) Oestrogen                               that the growth hormone is increased 3.4
                                              fold in endometriosis and 3.8 fold in
              Oestrogen is a group of
                                              endometrial adenocarcinoma. During this
       hormones that promotes the
                                              study banked tissue were selected, some
       reproductive system and secondary
                                              demonstrating cases of endometriosis and
       characteristics in females. They are
                                              some demonstrating normal uterine tissue.
       produced in the female ovaries, and
                                              The immunochemistry of each tissue was
       simulate the production of Follicle
                                              analyzed using different antibodies,
       Stimulating Hormone. For
                                              validated by previous studies. The
       endometriosis to occur oestregon
                                              endometric tissue showed an increase in
       needs to be present, therefore,
                                              immunolabelling of growth hormone and
       endometriosis is an oestrogen-
                                              interleukin-6 compared to normal tissue.
       dependant disease.
                                              “Our results suggest that both IL-6 and GH
                                              may play a role in the progression of both
                                              endometriosis and endometrial carcinoma
   2) Growth hormone and Growth-              (Slater 2006).
      Hormone releasing hormone

        Growth hormone is a hormone that
regulates growth and development in the       3) Gonadotropic Hormones
human body, produced by the pituitary. It’s
                                                     Gonadotropic Hormones are
involved in the increase of height, muscle
                                              hormones that are required for both male
mass, and body fat. Growth hormone is
                                              and female reproduction. These hormones
involved in the process of sexual
                                              stimulate the production and development of
differentiation, pubertal maturation and it
                                              the human reproductive system. There are
participates in gonadal steroidogenesis,
                                              two kinds of gonadotropic hormones:
gametogenesis, and ovulation (Slater et al.
                                              Luteinizing Hormone (LH) and Follicle
2006). Growth- Hormone Releasing
                                              stimulating hormone (FSH). These
Hormone is a peptide hormone produced by
                                              hormones are produced by the pituitary and
the hypothalamus, which stimulates the
                                              stimulate male and woman gonads. LH
release of Growth Hormone.
                                              stimulates sex steroid secretion. In women it
                                              stimulates the amount of estrogen produced
by the follicle cells and triggers ovulation by
controlling the menstrual cycle. FSH
                                                        Hypotalamus                 GnRH
stimulates the growth and maturation of the
ovarian follicles.

                                                                       Pituitary

a. Production of Gonadotropic Hormone
                                                                  LH               FSH
        The pituitary gland is located at the
base of the brain and is one of the glands
that compose the endocrine system. It is
divided into two lobes: the anterior lobe,                               Gonads
also called the anterior pituitary and the
posterior lobe. The posterior pituitary
secretes two different kinds of hormones
produced by the hypothalamus, oxytocin             Picture 2: Represent the sequence of
(OT) and antidiuretic hormones (ADH).             production of Gonadotropic Hormones to
        The anterior pituitary produces the       the reproductive system.
hormones it releases while the posterior
pituitary does not. The anterior pituitary is
located in the bone cavity at the base of the     b. Relationship with endometriosis
brain and produces six different kinds of
                                                           Gonadotropin releasing hormone is
hormones, such as Luteinizing Hormone and
                                                  used in the form of an agonist to treat
Follicle Stimulating Hormone. The
                                                  endometriosis pain, and is called
hypothalamus produces hormones that
                                                  Gonadotropin releasing hormone agonist. ,
stimulate the pituitary to produce other
                                                  . It is the most used and effective clinical
hormones. In this case, the hypothalamus
                                                  treatment for endometriosis pain.
produces Gonadotropin releasing hormone,
whose function is to stimulate the pituitary
to produce and release gonadotropic
hormones, such as LH and FSH by the
pituitary. Picture 2 can explain this process.
                                                  III. Treatments for endometriosis

                                                          Even though there are several kinds
                                                  of treatments for endometriosis, there is not
                                                  a definitive cure for it. Apart from surgery,
                                                  the treatments administered for
                                                  endometriosis are mostly to reduce pain.
                                                  Laparoscopy Surgery had been practiced to
                                                  remove the misplaced tissue but previous
studies have shown that this surgery is not            relief of pain about 4 week after
enough for the disease. Hormones had been              initiation of treatment” (Raffi and
used to control the thickening and bleeding            Amer 2010). It had been considered
of the tissue and are proved to be the most            to extend the months of treatment to
effective in pain reduction. (MedlinePlus              improve the effectiveness.
2011).

A. Hormonal treatments
                                                       Even though GnRH agonist is the
1. Growth hormone releasing hormone             most effective hormone treatment, it
agonist                                         contains several side effects. The most
                                                common side effect present in women who
     Gonadotropin releasing hormone             are undergoing GnHR therapy is the early
agonist is one of the most frequently           symptoms of menopause. When GnHR
administered treatments for reducing the        hormones turn off the ovaries, a pseudo-
pain produced by endometriosis. GnRH            menopause occurs. These women can
agonist inhibits the secretion of GnRH to the   experience hot flashes, mood swings,
gonadotrophs, which are secreted to the         vaginal dryness and in some cases
human gonads. There are seven types of          depression.
GnRH agonist that are used clinically to
treat endometriosis (leuprorelin, buserelin,            One of the most common concerns
goserelin, histrelin, deslorelin, nafarelin,    of GnRH therapy is the surge of
and triptorelin). In females, these hormones    osteoporosis. By using GnRH agonist,
work by turning off the ovaries causing a       estrogen is inhibited and lost and this is a
pseudo-menopause. They inhibit the effect       possible cause to produce osteoporosis.
of hormones that cause ovulation, especially    GnRH treatments can only be extended for
estrogen, and leads to inflammation and         six months. If they are extended too much,
pain. For women with endometriosis, GnRH        a great loss of estrogen may cause severe
agonist has proven to eliminate pain and        cases of osteoporosis.
reduce endometrial growth.

                                                        Studies conducted by the hospital
                GnRH agonist therapy            “Jose de San Martin” in Buenos Aires,
       consists of several injections or the    Argentina (Meresman et al. 2003) indicate
       application of nasal spray during        that GnRH may play an important role in the
       approximately three months. During       reduction of cell proliferation in
       the first two weeks of treatment the     endometriosis. Merseman and collaborators
       patient can experience worsening of      evaluated the effect of GnRH, especially
       the symptoms and irregular bleeding.     LA, on in vitro eutopic endometrial cell
       “About 80% of patients start to          proliferation. They concluded that GnRH
       experience improvement or complete       alone had no effect on basal DNA but
combined with TGFß it presented an                       Goldberg L, Rogol A, Sonksen P.
inhibitory effect on cell proliferation.        2009. Growth Hormone: Use and Abuse.
“GnRH-a appears to have a direct effect by      Hormones & You, The Hormone Fundation
enhancing the apoptotic index and               [internet];[unknown];[cited 2009 june].
decreasing the cell proliferation in            Available in: http://www.hormone.org/
endometrial cells” (Meresman et al. 2003).      Resources /upload/growth-hormone-use-
                                                and-abuse-bilingual-052509.pdf
III. Discussion
                                                       Infoplease [Internet].[2007].
         Endometriosis is a common disease      USA:Columbia University Press;[unknown].
affecting females of reproductive age.          Available in: http://www.
Endometrial tissue starts to grow outside the   infoplease.com/ce6/sci/A0821232.html
uterus causing severe pain and infertility.
Even though there are some theories that               Mayo Clinic [Internet].[2011].
could explain the cause of endometriosis,       USA:Mayo Foundation for Medical
the exact cause of it is still unknown.         Education and Research;[unknown].
Several hormones had been related not only      Available in: http://www.
to the development of endometriosis but also    mayoclinic.com/health/drug-
                                                information/DR600403
to it treatments. Previous studies have
shown a direct relationship of growth                   MedlinePlus. 2011. USA:
hormones during the development of              Department of Health and Human
endometriosis. Several treatments had been      Services,National Institutes of
applied to treat endometriosis, but there is    Health.[unknown].Available in:
no definitive cure for it. Hormonal             http://www.nlm.nih.gov/medlineplus/spanis
treatments are the most utilized to reduce      h/ency/article/000915.htm
and treat endometriosis pain and growth.
GnRH agonist therapy is the most effective
and most frequently used hormonal
treatment for it.
                                                        Meresman G, Bilotas M,Buquet
                                                R,Baraño R,Sueldo C,Tesone
                                                M.2003.“Gonadotropin- releasing hormone
                                                agonist induces apoptosis and reduces cell
References                                      proliferation in eutopic endometrial cultures
        Endometriosis Therapy [internet];       from women with endometriosis”. Fertility
[unknown]. Washington (GA):Biggerstaff B        and sterility. [Internet];[revised 2002 May
III; [unknown]. Available in:                   17] Vol 80: Available in: http://www.s
http://www.endometriosistherapy.com/conta       ciencedirect.com/science/article/pii/S001502
ctus.asp                                        8203007696
Mona.Endometriosis-what is it          http://www.viveplena.com/index.php?
[video].USA:icyou, A Benefitfocus             option=com_content&view=article&id=42:e
Company. Available in:                        stadisticas-en-endometrio sis&catid
http://www.youtube.com/user/icyouhealth#p/s
                                              =2:seccespecialista&Itemid=6
earch/0/pVrKiBUPoL4

        National Institute of Health
[Internet].[unknown].USA: National
Institute of Health;[unknown]. Available
in:http://www.nichd.nih.gov/health/topics/E
ndometriosis.cfm


        Raffi F, Amer S. 2010.
Endometriosis.Obstertrics, Gynecology and
Reproductive Medicine
[Internet];[unknown]. Available in: Science
Direct.


        Rose G.2005.What is
endometriosis.Women’s Health Medicine
[Internet];[unknown].Available in:Science
Direct

         Slater M,Copper M,Murphy CR.
2006. Human Growth Hormone and
Interleukin-6 are Unregulated in
Endometriosis and
Endometriod Adenocarcinoma.Acta
Histochemica [internet];[revised 2005 Oct
5];[cited 2008 Jan 18].108,13-18:Available
in: http://www.sciencedirect.com/ science
/article/pii/S0065128106000158

        The hormone foundation
[Internet].[2011].Connecticut: The hormone
foundation;[cited unknown].
http://www.hormone.org/Endo101/page2.cf
m

        Villalobos S.2009.”Estadísticas en
endometriosis”ENDO vive
plena.[Internet];[uknown];[2009 july 6].

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hormonal influence in endometriosis

  • 1. Hormonal influence in Endometriosis Nicole Colón Carrión Universidad de Puerto Rico, Cayey 1 Endometriosis is one of the most common diseases present in women of reproductive age. This paper aims to explain the influence of hormones in endometriosis development and treatments. Several hormones, such as oestrigen, GnHR and GnH, are mentioned and studied. Several Hormone treatments are used to reduce pain caused by endometriosis. This paper also explains the effect of GnRH agonist in endometrial tissue. Endometriosis, also called Endo, is the menstrual blood flows back through the presence of endometrial tissue outside the fallopian tubes and enters the pelvic or uterine cavity. It is a condition where the abdominal cavities instead of flowing out endometrial tissue is misplaced and grows in through the vagina. Another theory is that it other places outside the uterus, such as the pelvic and abdominal areas. These can be caused by Coelomic Metaplasia, a endometrial tissues thicken and bleed during process in which undifferentiated cells a process called menstruation. When develop into endometrial cells. endometriosis occurs this tissue continues to Endometriosis could be a hereditary disease; bleed, accumulating blood outside the uterus women with family history in endometriosis and causing inflammation and pain. “It’s could be more prone to develop this disease. difficult to point out the exact percentage of Some researchers are exploring the patients that suffer from endometriosis; in general, we speak of 10% of the female possibilities of hormones being related to the population of reproductive age” ( Vilalobos development of endometriosis. 2009). Endometriosis can affect any menstruating woman; it can appear at her Endometriosis can cause severe pain first period until menopause or at the middle in the abdominal and pelvic areas and of her reproductive age. The exact cause of infertility. “Endometriosis pain tends to get endometriosis is still unknown. worst as time goes on, it can be mild, modern or severe” (Mona, [unknown]). The “Because we don’t know why some amount of pain that endometriosis can cause women have endometriosis and others don’t, is not proportional to the amount of tissue we don’t know the cause of it” (Mona, the body contains. Some women may [unknown]). Even though the exact cause of present severe pain having small quantity of endometriosis is still unknown there are tissue, while others present extensive some theories that could explain the reason endometriosis tissue and have little or no for it. One of the theories is that pain at all. Infertility is not a side effect that endometriosis may be caused by Retrograde all endometriosis patients will present but Menstruation. Sampson postulates in 1920s it’s said that about 30% of woman who that endometriosis is caused by retrograde suffer from endometriosis will have it. “The menstruation; a process in which the
  • 2. findings of physical examination can be as a. Relationship with endometriosis diverse as the symptom complex of the history” (Rose,2005) Growth hormone releasing hormone (GHRH) and GH hormone promote endometrial proliferation and may be involved in the pathogenesis of ovarian and II. Hormones related to endometriosis endometrial cancer such as endometriosis (Khorram et al. 2001; Schindler 2004; Slater et al. 2006). Slater (2006) concluded 1) Oestrogen that the growth hormone is increased 3.4 fold in endometriosis and 3.8 fold in Oestrogen is a group of endometrial adenocarcinoma. During this hormones that promotes the study banked tissue were selected, some reproductive system and secondary demonstrating cases of endometriosis and characteristics in females. They are some demonstrating normal uterine tissue. produced in the female ovaries, and The immunochemistry of each tissue was simulate the production of Follicle analyzed using different antibodies, Stimulating Hormone. For validated by previous studies. The endometriosis to occur oestregon endometric tissue showed an increase in needs to be present, therefore, immunolabelling of growth hormone and endometriosis is an oestrogen- interleukin-6 compared to normal tissue. dependant disease. “Our results suggest that both IL-6 and GH may play a role in the progression of both endometriosis and endometrial carcinoma 2) Growth hormone and Growth- (Slater 2006). Hormone releasing hormone Growth hormone is a hormone that regulates growth and development in the 3) Gonadotropic Hormones human body, produced by the pituitary. It’s Gonadotropic Hormones are involved in the increase of height, muscle hormones that are required for both male mass, and body fat. Growth hormone is and female reproduction. These hormones involved in the process of sexual stimulate the production and development of differentiation, pubertal maturation and it the human reproductive system. There are participates in gonadal steroidogenesis, two kinds of gonadotropic hormones: gametogenesis, and ovulation (Slater et al. Luteinizing Hormone (LH) and Follicle 2006). Growth- Hormone Releasing stimulating hormone (FSH). These Hormone is a peptide hormone produced by hormones are produced by the pituitary and the hypothalamus, which stimulates the stimulate male and woman gonads. LH release of Growth Hormone. stimulates sex steroid secretion. In women it stimulates the amount of estrogen produced
  • 3. by the follicle cells and triggers ovulation by controlling the menstrual cycle. FSH Hypotalamus GnRH stimulates the growth and maturation of the ovarian follicles. Pituitary a. Production of Gonadotropic Hormone LH FSH The pituitary gland is located at the base of the brain and is one of the glands that compose the endocrine system. It is divided into two lobes: the anterior lobe, Gonads also called the anterior pituitary and the posterior lobe. The posterior pituitary secretes two different kinds of hormones produced by the hypothalamus, oxytocin Picture 2: Represent the sequence of (OT) and antidiuretic hormones (ADH). production of Gonadotropic Hormones to The anterior pituitary produces the the reproductive system. hormones it releases while the posterior pituitary does not. The anterior pituitary is located in the bone cavity at the base of the b. Relationship with endometriosis brain and produces six different kinds of Gonadotropin releasing hormone is hormones, such as Luteinizing Hormone and used in the form of an agonist to treat Follicle Stimulating Hormone. The endometriosis pain, and is called hypothalamus produces hormones that Gonadotropin releasing hormone agonist. , stimulate the pituitary to produce other . It is the most used and effective clinical hormones. In this case, the hypothalamus treatment for endometriosis pain. produces Gonadotropin releasing hormone, whose function is to stimulate the pituitary to produce and release gonadotropic hormones, such as LH and FSH by the pituitary. Picture 2 can explain this process. III. Treatments for endometriosis Even though there are several kinds of treatments for endometriosis, there is not a definitive cure for it. Apart from surgery, the treatments administered for endometriosis are mostly to reduce pain. Laparoscopy Surgery had been practiced to remove the misplaced tissue but previous
  • 4. studies have shown that this surgery is not relief of pain about 4 week after enough for the disease. Hormones had been initiation of treatment” (Raffi and used to control the thickening and bleeding Amer 2010). It had been considered of the tissue and are proved to be the most to extend the months of treatment to effective in pain reduction. (MedlinePlus improve the effectiveness. 2011). A. Hormonal treatments Even though GnRH agonist is the 1. Growth hormone releasing hormone most effective hormone treatment, it agonist contains several side effects. The most common side effect present in women who Gonadotropin releasing hormone are undergoing GnHR therapy is the early agonist is one of the most frequently symptoms of menopause. When GnHR administered treatments for reducing the hormones turn off the ovaries, a pseudo- pain produced by endometriosis. GnRH menopause occurs. These women can agonist inhibits the secretion of GnRH to the experience hot flashes, mood swings, gonadotrophs, which are secreted to the vaginal dryness and in some cases human gonads. There are seven types of depression. GnRH agonist that are used clinically to treat endometriosis (leuprorelin, buserelin, One of the most common concerns goserelin, histrelin, deslorelin, nafarelin, of GnRH therapy is the surge of and triptorelin). In females, these hormones osteoporosis. By using GnRH agonist, work by turning off the ovaries causing a estrogen is inhibited and lost and this is a pseudo-menopause. They inhibit the effect possible cause to produce osteoporosis. of hormones that cause ovulation, especially GnRH treatments can only be extended for estrogen, and leads to inflammation and six months. If they are extended too much, pain. For women with endometriosis, GnRH a great loss of estrogen may cause severe agonist has proven to eliminate pain and cases of osteoporosis. reduce endometrial growth. Studies conducted by the hospital GnRH agonist therapy “Jose de San Martin” in Buenos Aires, consists of several injections or the Argentina (Meresman et al. 2003) indicate application of nasal spray during that GnRH may play an important role in the approximately three months. During reduction of cell proliferation in the first two weeks of treatment the endometriosis. Merseman and collaborators patient can experience worsening of evaluated the effect of GnRH, especially the symptoms and irregular bleeding. LA, on in vitro eutopic endometrial cell “About 80% of patients start to proliferation. They concluded that GnRH experience improvement or complete alone had no effect on basal DNA but
  • 5. combined with TGFß it presented an Goldberg L, Rogol A, Sonksen P. inhibitory effect on cell proliferation. 2009. Growth Hormone: Use and Abuse. “GnRH-a appears to have a direct effect by Hormones & You, The Hormone Fundation enhancing the apoptotic index and [internet];[unknown];[cited 2009 june]. decreasing the cell proliferation in Available in: http://www.hormone.org/ endometrial cells” (Meresman et al. 2003). Resources /upload/growth-hormone-use- and-abuse-bilingual-052509.pdf III. Discussion Infoplease [Internet].[2007]. Endometriosis is a common disease USA:Columbia University Press;[unknown]. affecting females of reproductive age. Available in: http://www. Endometrial tissue starts to grow outside the infoplease.com/ce6/sci/A0821232.html uterus causing severe pain and infertility. Even though there are some theories that Mayo Clinic [Internet].[2011]. could explain the cause of endometriosis, USA:Mayo Foundation for Medical the exact cause of it is still unknown. Education and Research;[unknown]. Several hormones had been related not only Available in: http://www. to the development of endometriosis but also mayoclinic.com/health/drug- information/DR600403 to it treatments. Previous studies have shown a direct relationship of growth MedlinePlus. 2011. USA: hormones during the development of Department of Health and Human endometriosis. Several treatments had been Services,National Institutes of applied to treat endometriosis, but there is Health.[unknown].Available in: no definitive cure for it. Hormonal http://www.nlm.nih.gov/medlineplus/spanis treatments are the most utilized to reduce h/ency/article/000915.htm and treat endometriosis pain and growth. GnRH agonist therapy is the most effective and most frequently used hormonal treatment for it. Meresman G, Bilotas M,Buquet R,Baraño R,Sueldo C,Tesone M.2003.“Gonadotropin- releasing hormone agonist induces apoptosis and reduces cell References proliferation in eutopic endometrial cultures Endometriosis Therapy [internet]; from women with endometriosis”. Fertility [unknown]. Washington (GA):Biggerstaff B and sterility. [Internet];[revised 2002 May III; [unknown]. Available in: 17] Vol 80: Available in: http://www.s http://www.endometriosistherapy.com/conta ciencedirect.com/science/article/pii/S001502 ctus.asp 8203007696
  • 6. Mona.Endometriosis-what is it http://www.viveplena.com/index.php? [video].USA:icyou, A Benefitfocus option=com_content&view=article&id=42:e Company. Available in: stadisticas-en-endometrio sis&catid http://www.youtube.com/user/icyouhealth#p/s =2:seccespecialista&Itemid=6 earch/0/pVrKiBUPoL4 National Institute of Health [Internet].[unknown].USA: National Institute of Health;[unknown]. Available in:http://www.nichd.nih.gov/health/topics/E ndometriosis.cfm Raffi F, Amer S. 2010. Endometriosis.Obstertrics, Gynecology and Reproductive Medicine [Internet];[unknown]. Available in: Science Direct. Rose G.2005.What is endometriosis.Women’s Health Medicine [Internet];[unknown].Available in:Science Direct Slater M,Copper M,Murphy CR. 2006. Human Growth Hormone and Interleukin-6 are Unregulated in Endometriosis and Endometriod Adenocarcinoma.Acta Histochemica [internet];[revised 2005 Oct 5];[cited 2008 Jan 18].108,13-18:Available in: http://www.sciencedirect.com/ science /article/pii/S0065128106000158 The hormone foundation [Internet].[2011].Connecticut: The hormone foundation;[cited unknown]. http://www.hormone.org/Endo101/page2.cf m Villalobos S.2009.”Estadísticas en endometriosis”ENDO vive plena.[Internet];[uknown];[2009 july 6].