Endometriosis

Avatar photoby — in Lupron Victims

“Endometriosis is present in approximately 5 percent of women of reproductive age.” — Robert L. Barbieri, MD
This represents approximately 4 million women in the U.S.
Far less than 1% of women with endometriosis belong to The Endometriosis Association.

I. “Associations” and Money from the Manufacturers of GnRH-a

There are 3 GnRH-a approved by the FDA in the United States for endometriosis:
They are:

  1. Lupron (leuprolide acetate) made by TAP Pharmaceuticals, Inc.
  2. Synarel (nafarelin acetate) made by Searle Pharmaceuticals
  3. Zoladex (goserelin acetate) made by Zeneca Pharmaceuticals

A. The Endometriosis Research Center

  • The Endometriosis Research Center’s “Director of Operations / Director” is the Coordinator of AstraZeneca Pharmaceutical’s Endometriosis Zone. Zeneca Pharmaceuticals is the maker of Zoladex, a GnRH-a.
  • The Endometriosis Research Center advertises a study for Lupron and add-back. The National Lupron Victims Network considers this promotion for the use of Lupron. More information about Lupron and add-back will be coming soon.

B. The Endometriosis Association

When the 1st GnRH agonist was being approved in the United States the following appeared in an Endometriosis Association newsletter (1989, Vol. 10 #2):

The Endometriosis Association “received word that nafarelin [Synarel the 1st GnRH-a approved for endo] might not be approved for endometriosis because some members of the committee [which included a couple of endometriosis specialists plus ob/gyns and others] did not consider endometriosis a severe enough disease to warrant approval of such a SERIOUS drug ” According to the newsletter, Mary Lou Ballweg of the Endometriosis Association “submitted a powerful written statement advocating approval [of this SERIOUS drug].” It is interesting to note that the Endometriosis Association claimed that they “helped gain approval for a drug, the 1st GnRH drug approved for endometriosis.”

The following statements appeared in Endometriosis Association newsletters:

  1. The Endo Association in their 1998 newsletter Volume 19 #1-2 stated, “We also are immensely appreciative of our corporate donors…:
    Zeneca Pharmaceuticals (makers of Zoladex), for $58,660, an unrestricted educational grant to support our major research survey and data presentation at the VI World Congress on Endometriosis and reestablishment of our data research registry; also for their generous support of our international panel at the VI World Congress on Endometriosis.
    TAP Pharmaceutical (makers of Lupron) [a GnRH-a], for $30,000, unrestricted grant.
    Searle Pharmaceutical (makers of Synarel) [a GnRH-a], for $20,000 unrestricted grant, as well as for $6,000 support for the Association’s scientific brainstorming sessions at the World Congress on Endometriosis.”
  2. An Endo Association newsletter, (1998, Vol. 19, #1-2), revealed that the Endo Association received over $114,000 from the 3 manufacturers of GnRH analogs during that year.
  3. During the year 1997-1998 (1999, Vol. 19, #5-6), “membership” was $220,285.
  4. The amount of money the Endo Association received from the 3 manufacturers of GnRH analogs was significant.
  5. The Endo Association in their 1997 newsletter Volume 18 #1 stated, “We also greatly appreciate the following companies which provided contributions to the Association. Thank you so much to:
    TAP Pharmaceutical (makers of Lupron) [a GnRH-a], for $20,000.
    Searle Pharmaceutical (makers of Synarel) [a GnRH-a], U.S. Branch, for $5,425.
    Searle Pharmaceutical, Canada Branch, for $1,125.”
  6. The Endo Association in their 1995 newsletter Volume 16 #1 stated, “We also want to express our great appreciation to our corporate donors. Your support is very important to us! Thank you so much to:
    * TAP PHARMACEUTICALS (makers of Lupron) [a GnRH-a], for $23,000 in support of all the printing for the 15th Anniversary Conference and for meals for the speakers.
    SYNTEX LABORATORIES (now part of Hoffman-LaRoche) [makers of the GnRH-a, Synarel] for $10,000 in support of the 15th Anniversary Conference planning (vital start-up funds!)
    ZENECA PHARMACEUTICALS (U.S.) (makers of Zoladex) [another GnRH-a] for $6,000 in support of an educational mailing to all ob-gyn nurses.”
  7. The Endo Association in their 1995 newsletter Volume 16 #1 stated, “Recently we wrote to every gyn in the U.S., thanks to a grant from Syntex Laboratories [makers of the GnRH-a Synarel], and offered the opportunity to join the Physician Member Registry.”
  8. The Endo Association in their 1997 newsletter Volume 18 #1 stated, “We are deeply grateful to [x] and Searle [makers of the GnRH-a Synarel] Canada for their support of Endometriosis Awareness Week (distributing ribbons in English and French to physicians across Canada and supporting a special mailing of the ribbons to all of our members across Canada); including a poster on endometriosis to the physicians; and carrying out a highly successful mailing to Canadian ob/gyns offering the Associations brochures, books and a videotape free to the physicians (paid for by Searle [makers of the GnRH-a Synarel]).”
  9. The Endo Association in their 1997 newsletter Volume 18 #5-6 stated, “We are also pleased to work with Searle [makers of the GnRH-a Synarel] Canada in an effort to provide Association literature to Canadian physicians-almost 400 books, 285 videos, and over 7,000 brochures in 14 languages.”
  10. The Endo Association in their 1996 newsletter Volume 17 #5-6 stated, “Nursing outreach efforts continue through the efforts of the EA Nurses’ Council and a grant from Zeneca [makers of the GnRH-a Zoladex] which allowed an education mailing to nurses throughout the United States.
  11. The Endo Association in their 1995 newsletter Volume 16 #2 stated, “Thanks to [x]…for her work on our recent mailing to women’s health nurses across the US (sponsored by a grant from Zeneca [makers of the GnRH-a Zoladex]).
  12. The Endo Association in their 1996 newsletter Volume 17 #5-6 stated, “In the fall of 1995, the winners were announced for the EA Journalism Awards for outstanding reporting on endo. Winners were awarded $1000 each for stories on endo written from July 1994 to July 1995. Sponsored by the EA and funded by TAP Pharmaceuticals [makers of the GnRH-a Lupron] the contest was designed to encourage accurate reporting on endo.”
  13. The Endo Association in their 1996 newsletter Volume 17 #1 stated, “Journalism Award Winners. We’re happy to announce the winners of the Endometriosis Association Journalism Awards for outstanding reporting on the disease.” “Each of the winners received $1000. Thank you to all those who entered and to all the journalists who have worked to get accurate information about endometriosis into the public eye. We especially appreciate TAP Pharmaceuticals [makers of the GnRH-a Lupron],whose support made the award program possible.”
  14. The Endo Association in their 1995 newsletter Volume 16 #2 stated, “Thank you to our judges for the Endometriosis Association Journalism Awards contest (sponsored by TAP Pharmaceuticals [makers of the GnRH-a Lupron])…”
  15. The Endo Association in their 1996 newsletter Volume 17 #1 stated, “Central New York Support Group leaders [x] and [x] thank Tap Pharmaceuticals [makers of the GnRH-a Lupron] and local rep [x], [x], for their 1995 donation earmarked for the group’s mailings and newletter. Thanks also to Zeneca Pharmaceuticals [makers of the GnRH-a Zoladex] and local rep [X], [X], for their 1996 donation for monthly mailings and press releases.”
  16. The Endo Association in their 1995 newsletter Volume 16 #2 stated, “Congratulations to our Munich, Germany Support Group for its very successful first conference in September!” “Conference organizers [x] and [x] would like to especially thank representatives from Zeneca Gmbh, Organon GmbH, and Takeda Pharma [TAP is a joint venture between Takeda Pharma and Abbott Pharmaceuticals] GmbH for their help and sponsorship.”
  17. The Endo Association in their 1995 newsletter Volume 16 #1 stated, “The Honolulu Support Group held their fist day-long conference during Endometriosis Awareness Week in March. The group leaders, [x] and [x], worked hard to arrange sponsorship from local pharmaceutical reps around Oahu (including TAP [makers of the GnRH-a Lupron] and Zeneca [makers of the GnRH-a Zoladex])…”
  18. The Endo Association in their 1997 newsletter Volume 18 #5-6 stated, “We deeply appreciate the unrestricted educational grant from Zeneca Pharmaceuticals [makers of the GnRH-a Zoladex], which gave us this opportunity to once again survey a large number of women with endometriosis.”
  19. The Endo Association in their 1995 newsletter Volume 16 #1 stated, “We have received a quantity of the 257-page medical textbook, Endometriosis: the Enigmatic Disease, from Syntex Laboratories [makers of the GnRH-a Synarel].”
  20. The Endo Association in their 1996 newsletter Volume 17 #5-6 stated, “We are pleased that top-ranked tennis star [x], who suffers from endo, has agreed to serve as spokesperson to increase awareness of the disease. The campaign was launched during Endometriosis Awareness Week last spring and recently picked up steam with articles in Teen Magazine, Detroit free Press, and other publications. Thank you to the U.S. branch of Zeneca Pharmaceuticals, manufacturers of Zoladex, for sponsoring this campaign!”
  21. The Endo Association in their 1997 newsletter Volume 18 #5-6 stated, “Thanks to grants from Zeneca Pharmaceuticals, makers of Zoladex, and Searle, makers of Synarel, the Association is organizing a special workshop on Living With, Treating, and Studying Endometriosis: New Perspectives for the VIth World Congress on Endometriosis in Quebec this summer.”
  22. The Endo Association in their 1997 newsletter Volume 18 #3-4 stated, “The Endometriosis Association had been granted space to promote its causes by FIGO officials and gracious sponsorship for travel and shipping by Zeneca Pharmaceuticals” [makers of the GnRH-a Zoladez].
  23. The Endo Association in their 1997 newsletter Volume 18 #3-4 stated under “Fundraising angels… And Zeneca Pharmaceuticals [makers of the GnRH-a Zoladez] for $6500 to support EA’s outreach work at FIGO in Denmark.”
  24. The Endo Association in their 1991 newsletter Volume 12 #5 stated, “we requested grant assistance from Syntex (U.S.) [makers of the GnRH-a Synarel] to fund another public service announcement (PSA). We are very pleased and appreciative that Syntex agreed to do this.”
    “The PSA is now ready and by the time you receive this newsletter, evry T.V. station in the U.S. will have received a mailing from us offering the announcement. Hopefully, many of the stations will agree to air the PSA to help women with endometriosis learn about the help available from the EA. The PSA earmarks undiagnosed women.”
  25. The Endo Association in their 1999 newsletter Volume 20 #1 stated, “Thanks to Takeda Pharma GmbH, Germany for sponsoring the printing and distribution of the EA’s revised German brochure, and Schering AG, Germany, whose donation enabled us to be represented at the European Society for Human Reproduction and Embryology (ESHRE) meeting in France.
  26. The Endo Association in their 1999 newsletter Volume 19 #5-6 stated, “Thanks to Takeda Pharma GmbH, Germany, and Laboratoires Takeda, France, for making it possible for the Association to be represented at the ‘Fifth International Symposium on GnRH Analogs’ in Geneva.”
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TV Infomercial

In 1998 there was a 15 minute infomercial on national cable television promoting GnRH analogs. For approximately 15 minutes the infomercial “plugged” GnRH analogs even for unapproved uses. The only statement made regarding side-effects was “If side effects should occur we can treat that as well.” The infomercial was made possible through an educational grant from TAP Pharmaceuticals, Inc. (the manufacturer of Lupron) [a GnRh-a] At the end of the ad there was a full screen showing the 800# for the Endometriosis Association.

II. The Lines Used To Persuade You To Use Lupron

  1. If someone tells you … Lupron WORKS BY putting you into menopause and then, in the same breath, says DON’T have a hysterectomy because menopause doesn’t work … You are hearing a sales pitch. Think about it…menopause doesn’t work, but, Lupron works by putting you into menopause.How illogical!
  2. If someone tells you … Try Lupron because there is NO CURE for endometriosis … You are hearing a sales pitch. Surgery can cure endometriosis. Lupron can NOT cure endometriosis. According to Dr. David Redwine, a leading expert in endometriosis:
      1. “Endometriosis can be cured by conservative surgery.”
      2. “Endometriosis can only be cured by surgery.”
      3. “Surgical cures have been documented in the medical literature.”
      4. “Conservative surgery for excision of endometriosis was viewed as curative in the 1940’s and 50’s.”
  3. If someone tells you … All drugs have side effects, even Tylenol … You are hearing a sales pitch. Saying that all drugs have side effects, even Tylenol, is like saying any state in the United States can have an earthquake. It is true. But, now try and convince an insurance company that the RISKS are the same and the premium for earthquake insurance should be the same in California as in New York! Yes, New York HAS HAD earthquakes. But don’t try to compare it to California as far as RISK. And yes, Tylenol has side effects. But don’t try to compare it to Lupron as far as RISK. BILLIONS, if not trillions, of doses of Tylenol have been consumed by the majority of Americans. If someone wants you to believe that the number of side-effects and safety of Lupron is equal to the number of side-effects and safety of Tylenol, you’re hearing a “sales pitch!”

III. Lupron Is NOT A CURE For Endometriosis

  • Lupron is not a cure for endometriosis. According to the to US Food and Drug Administration documents, “Overall, all analogues [Lupron] work similarly, to suppress symptoms and signs of endometriosis, but as with other [drug] treatments, represent a temporary relief of disease process rather than a cure.”
  • According to Dr. David Redwine, a leading expert in endometriosis:
    1. “Endometriosis can be cured by conservative surgery.”
    2. “Endometriosis can only be cured by surgery.”
    3. “Surgical cures have been documented in the medical literature.”
    4. “Conservative surgery for excision of endometriosis was viewed as curative in the 1940’s and 50’s.”
  • In 1995 John Hopkins Hospital did a study of 138 patients with endometriosis who underwent a hysterectomy between 1979 and 1991.Follow-up information was obtained.
    Of 109 who had all ovarian tissue removed:
    11 (10%) had recurrent symptoms
    4 (3.7%) required reoperation
  • A US Food and Drug Administration reviewer stated there are many problems “with the premise [idea] of treating endometriosis for 6 months.” “Endometriosis is a chronic condition. How will 6 months of treatment affect the long-term outcome of the disease?”
  • Dr. Waller et al stated that “endometriosis seems, for many women, to be a recurrent disease throughout reproductive life or until oophorectomy [removal of the ovaries] is performed.”
  • Dr. Barbieri et al stated that “the only therapy for endometriosis that is not associated with a high recurrence rate is bilateral oophorectomy [removal of both ovaries].”
  • Mettler et al stated that “Oophorectomy is the most effective treatment for endometriosis.”
  • Dr. Dawood stated that “The most effective treatment of endometriosis is removal of both ovaries.”
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IV. Lupron Does Not Help Infertility Due To Endometriosis

  1. “Both our study and the meta-analysis show that either no treatment or surgery is superior to medical [drug] treatment for minimal and mild endometriosis associated with infertility. For moderate and severe disease, surgery is usually used.”
  2. According to the to US Food and Drug Administration documents, “Lupron Depot has no effect on pregnancy rates and should not be used as a fertility promoting drug.”
  3. According to the to US Food and Drug Administration documents, “The analogues [Lupron] are not indicated for infertility associated with endometriosis, since there are no data to show that treatment with analogues in any way alters fertility outcomes.”
  4. According to the to US Food and Drug Administration documents, “There is no evidence that pregnancy rates are enhanced” by the use of Lupron Depot.
  5. Although mild or minimal endometriosis appears to reduce fertility, there is increasing evidence that treatment with GnRH agonists or danazol does not increase the fertility of women with these minor degrees of endometriosis.”
  6. Trials comparing gestrinone, GnRH-a, or an OC pill with an active control, danazol, demonstrated no difference in subsequent fecundity [fertility] between groups.”
  7. The common OR [odds ratio] for pregnancy after ovulation suppression (MPA, gestrinone, or GnRH agonist) versus danazol was also nonsignificant: 1.07.”

V. Problems With the Studies Used By The FDA To Approve Lupron For Endometriosis

The US Food and Drug Administration (FDA) approves drugs based on SAFETY and EFFICACY for a particular use.

Lupron Depot (3.75 mg per month) was approved by the US FDA for endometriosis in 1990. The FDA’s New Drug Application (NDA) #20-011 contains information about the approval of Lupron for endometriosis. (See Studies below)

According to the package insert:

  1. “Experience with Lupron Depot for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months.”
  2. “Retreatment can not be recommended since safety data beyond 6 months are not available.”

This is a total lifetime dose of 22.5 mg (3.75 mg x 6 months = 22.5 mg)

Formal dosing studies were never done

According to US Food and Drug Administration documents:

  1. “Treatment of pain of endometriosis is probably the only valid use of the analogues, since the clinical significance of decrease in endometrial implants are not known at this time.”
  2. “Much of the efficacy analyses were performed on the revised AFS scoring system. The value of this scoring system in predicting long-term outcome, either symptom relief or pregnancy is probably not good.”

The information regarding the approval of Lupron by the FDA for endometriosis appears in NDA [New Drug Application] #20-011. NDA (20-011) consists of 2 studies. The 2 studies were:

A. M86-031 (Lupron Depot vs. Placebo)

This study was supposed to be a controlled, double-blind, placebo study. However, “because of the high drop out rate (by patients in the study), this study can only be viewed as a supportive study and not as a separate controlled study
Therefore, no controlled, double-blind, placebo safety studies were done prior to the approval of Lupron by the FDA, for endometriosis. The objective of the study was to evaluate the safety and efficacy (effectiveness was improvement in pain) of Lupron Depot vs. Placebo.

  • 32 women received Lupron
  • Of the 32 women who received Lupron:
    1. 4 were Complete Exclusions:
      “It was subsequently determined that they had failed to meet entrance criteria or because they received less than 3 injections of Lupron.”
    2. 7 were Partial Exclusions:
      “Non-compliance with intended study procedures and dosing regimens.”
    3. 3 were Premature Terminations:
      3 of the Lupron patients discontinued because of pain or adverse events.
  • According to the FDA documents (Study #M86-031):
    1. A very high percentage of patients showed improvement with placebo (a blank):
      38 % had improvement of dysmenorrhea (painful menstruation) with placebo.
      43 % had improvement of pelvic pain with placebo.
      30 % had improvement of dyspareunia (painful sex) with placebo.
      33 % had improvement of pelvic tenderness with placebo.
      50 % experienced improvement of pelvic induration (pelvic hardness) with placebo.
  • Women were allowed to take narcotics at the same time that they were evaluating Lupron for pain relief. “Although NOT DESIRABLE, analgesic use will be recorded as: none, non-narcotic, MILD NARCOTIC (codeine), STRONG ORAL NARCOTIC (e.g. Dilaudid) and PARENTERAL NARCOTIC.”
    “Frequency of analgesic use per day will also be recorded.”
    No significant value was attached to the data regarding the difference in narcotic use between the Lupron treated group and the placebo treated group in Study M86-031.
  • “After 12 weeks [3 months] of treatment, if significant pain was present, the patient was considered a treatment failure.”
  • “Symptom severity changes with treatment are a measure of treatment success, especially since the FMHDG Advisory committee approved [the first GnRH-a] as a treatment only for pain of endometriosis. However, problems with the scoring of symptoms are many, since the symptoms are recorded by recall at the end of a month. Recall biases and problems [memory loss] can influence such data collection. A daily log would have been a more accurate measure of changes with treatment.” “The lack of daily records and records containing only those obtained by recall once a month make it difficult to provide adequate information about symptoms.”(M86-039)
  • “There are abnormalities of liver tests, namely, ALK PHOS, SGOT, SGPT, CPK, and to a lessor degree, LDH, with Lupron treatment.”

VI. An Attempt To Blame The Bone Loss From GnRH-a On Endometriosis?

Dr. Florence Comite was the lead investigator conducting experiments with GnRH-a on children with precocious puberty at the NIH. Comite also participated in the following studies in an attempt to gain FDA approval of Lupron: endometriosis, fibroids, and precocious puberty.

Endometriosis:
Study # M86-031 – Comite investigated 16% of all patients in this study.
Study # M86-039 – Comite participated in this study.
Fibroids:
Study #M86-062 – Comite investigated 36% of all patients in this study.
Comite is an author of the Leuprolide Study Group (fibroids). Dr. Comite is also the author of 14 articles involving GnRH-a including the following:

  1. The NIH experience with precocious puberty; diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy.
  2. Luteinizing hormone releasing hormone analogue therapy for central precocious puberty. Long-term effect on somatic growth, bone maturation, and predicting height.
  3. GnRH analogs and safety.

Dr. Comite has researched Lupron and other GnRH-analogues and is aware of the negative impact they have on bone density (see above). In 1989, Comite et al stated that “an association between endometriosis and reduced bone mass has NOT been observed previously.” Despite this knowledge Dr. Comite et al wrote an article entitled “Reduced Bone Mass In Reproductive-Aged Women with Endometriosis.”

Dr. Comite et al compared mean bone mass values in women with endometriosis to mean bone mass values in “normal women.” In the article, she made a point of noting that “within a 3-month period before the study, none of the patients had taken… danazol, or GnRH analog.” Lupron is a GnRH analog. Later in the article, Dr Comite et al stated that “patients with [any] prior exposure to danazol… were excluded from this study.”

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Five years later in another article, Dr. Dochi stated that Comite et al “included women who previously had been treated with GnRH agonists and these agonists are associated with bone loss.” It is disturbing that Dr. Comite, an experienced researcher, never took into account and never stated that her subjects had been exposed to GnRH analogs when she concluded that “women with endometriosis had significantly decreased cortical and trabecular bone mass.” She stated that, “we have seen a highly statistically significant difference of bone mass in relatively young women with endometriosis ([a decrease of] 10% of their cortical bone and over 15% of the trabecular bone).” “This decrease in cortical and trabecular bone, while not yet resulting in an increase in fractures, is similar to that observed in the perimenopausal period, and yet these young women of child-bearing age with endometriosis will not be undergoing menopause for another 20 years.” “Nonetheless, this finding of reduced bone mass in the wrists of women with a mean age of 30 yr is significant.” “The possibility of either reversing this process or at least halting the continuation of the bone loss has enormous significance for these young women.”

In 1994, nearly 5 years after Dr. Comite’s study, Dr. Dochi in England reported the results of his study. Dr. Dochi stated that “women with previous exposure to danazol or any GnRH agonists were excluded from this study.” Dochi concluded that in contrast with the findings of Comite et al., the results from “this study indicate that women with endometriosis do not have reduced bone density compared with age-matched controls. One explanation for the difference between the results of this study and those of Comite et al. is that they included women who previously had been treated with GnRH agonists and these agonists are associated with bone loss.” “In conclusion, we found NO evidence of low bone density in women with untreated endometriosis and they are therefore not a high risk group for future postmenopausal osteoporosis.”

And finally, it should be noted that it is NOT just women with endometriosis that experience bone loss from Lupron. Women with fibroids, children with precocious puberty, and men with prostate cancer have all experienced bone loss after exposure to a GnRH-analog [ie: Lupron]; drugs known to cause decreased bone density. Dr. Comite’s study should serve as a warning to people who have taken Lupron!

REFERENCES

  1. US Food and Drug Administration. New Drug Application #20-011.
  2. Dlugi AM, Miller JD, Knittle J, Lupron Study Group, Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Fertility & Sterility. 1990; 54: 3: p. 419-424.
  3. Physicians Desk Reference 1996.
  4. Namnoum AB, Hickman TN, Goodman SB, Gehlbach DL, Rock JA. Incidence of symptom recurrence after hysterectomy for endometriosis. Fertility & Sterility. 1995; 64: 5: p. 898-902.
  5. Waller KG, Shaw RW. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertility & Sterility. 1993; 59: 3: p. 511-515.
  6. Barbieri, RL. New Therapy for Endometriosis. The New England Journal of Medicine. 1988; 318: 8: p. 512-514.
  7. Werlin LB, Hodgen GD. Gonadotropin-Releasing Hormone Agonist Suppresses Ovulation, Menses, and Endometriosis in Monkeys: An Individualized, Intermittent Regimen. Journal of Clinical Endocrinology and Metabolism. 1983; 56: p. 844-848.
  8. The Endometriosis Association Newsletter. 1995; Vol 16 No. 1
  9. The Endometriosis Association Newsletter. 1997; Vol 18 No. 1
  10. Comite F, Delman M, Hutchinson-Williams K, DeCherney AH, Jensen P. Reduced Bone Mass in Reproductive-Aged Women with Endometriosis. Journal of Clinical Endocrinology and Metaboloism. 1989; 69: 4: p. 837-842.
  11. Dochi T, Lees B, Sidhu M, Stevenson JC. Bone density and endometriosis. Fertility & Sterility. 1994: 61: 1: p. 175-177.
  12. US Food and Drug Administration. New Drug Application # 19-943.
  13. Leuprolide Study Group
  14. Pescovitz OH, Comite F, Hench K, Barnes K, McNemar A, Foster C, Kenigsberg D, Loriaux DL, Cutler GB. The NIH experience with precocious puberty; diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy. The NIH experience with precocious puberty: Diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy. The J of Ped. 108: 1: 1986; p. 47-54.
  15. Comite F, Cassoria F, Barnes KM, Hench KD, Dwyer A, Skerda MC, Loriaux DL, Cutler GB, Pescovitz OH. Luteinizing hormone releasing hormone analogue therapy for central precocious puberty. Long-term effect on somatic growth, bone maturation, and predicting height. JAMA. 255: 19: 1986; p. 2613-2616.
  16. Comite F. GnRH analogs and safety. Obstetrical and Gynecological Survey. pp.319-325.
  17. Surrey
  18. Tzingounis VA, Cardamakis E. Modern Approach to Endometriosis. Annal New York Academy of Sciences. p. 320-330.
  19. Fraser IS. GnRH agonists for endometriosis. The Medical Journal of Australia. 1995; 162: p.61-62.
  20. Hughes EG, Fedorkow DM, Collins JA. A quantitative overview of controlled trials in endometriosis-associated infertility. Fertility and Sterility. 1993; 59: 5: p.963-970.
  21. Wheeler JM, Knittle JD, Miller JD. Depot leuprolide verus danazol in treatment of women with symptomatic endometriosis. Am J Obstet Gynecol. 1992; 167: 5: p. 1367-1371.
  22. Barbieri RL. New Therapy For Endometriosis. The New England Journal of Medicine. 1988; 318: 8: p. 512-513.
  23. Dawood MY, Ramos J, Khan-Dawood, FS. Depot leuprolide acetate versus danazol for treatment of pelvic endometriosis: changes in vertebral bone mass and serum estradiol and calcitonin. Fertility and Sterility. 1995; 63: 6: p. 1117-1183.
  24. Adamson GD, Pasta DJ. Surgical treatment of endometriosis-associated infertility: Meta-analysis compared with survival analysis. Am J Obstet Gynecol. 1994; 171: 6: 1488-1502.
  25. Kennedy SH, Williams IA, Brodribb J, Barlow DH, Shaw RW. A comparison of nafarelin acetate and danazol in the treatment of endometriosis. Fertility and Sterility. 1990; 53: 6: p. 998-1003.
  26. Mettler L, Steinmuller H, Schachner-Wunschmann E. Experience with a depot GnRH-agonist (Zoladex) in the treatment of genital endometriosis. Human Reproduction. 1991; 6: 5: p. 694-698.
  27. American Hospital Formulary Service. 1997.
  28. Dawood MY. Impact of medical treatment of endometriosis on bone mass. Am J Obstet Gynecol 1993; 168: 2: p.674-684.
  29. Redwine, David B. Written communication (1999) reprinted with permission.
  30. Miller JD, Shaw RW, Casper RFJ, Rock JA, Thomas EJ, Dmowski WP, Surrey E, Malinak LR, Moghissi K. Historical prospective cohort study of the recurrence of pain after discontinuation of treatment with danazol or a gonadotropin-releasing hormone agonist. Fertility & Sterility. 1998; 70: 2: p. 293-296.
  31. Evers JLH. The second-look laparoscopy for evaluation of the result of medical treatment of endometriosis should not be performed during ovarian suppression. Fertility & Sterility. 1987; 47: 3: p. 502-504.
  32. Redwine DB. Nafarelin Versus Danazol Versus Surgery. Fertility & Sterility. 1992; 58: 2: p. 455-456.
  33. Endometriosis: The Disease And Its Treatment. TAP Pharmaceuticals, Inc.; 1994.
  34. Physicians Desk Reference. 1998; p. 2908.

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