i'm supposed to do a costing here but never got round to doing it.
total i estimated so far we have forked out more than $2000, excluding out of pocket expenses such as taxi fares to and from the hospital.
will do a break down later.
Thursday, July 26, 2007
Start of Puregon stage
Finally got the go ahead to start with stimulations stage. need to jab 200 units of puregon every day for next 7 days before heading for scan to check growth of follicles.
in the meantime, suppose to continue with lucrin as well, that means 2 jabs every morning. oh great!
the puregon injection pen takes some taking use to - i still prefer the old fashion syringe but then since puregon cost like $120 per jab, it's better to have a mechanised measurement. oh yeah, due to the longer time to jab lucrin, i had to get a new bottle of lucrin as well.
calculating ER should be on 3rd or 6th Aug....cross fingers, follicles grow well otherwise it's going to get expensive if need to increase puregon dose.
in the meantime, suppose to continue with lucrin as well, that means 2 jabs every morning. oh great!
the puregon injection pen takes some taking use to - i still prefer the old fashion syringe but then since puregon cost like $120 per jab, it's better to have a mechanised measurement. oh yeah, due to the longer time to jab lucrin, i had to get a new bottle of lucrin as well.
calculating ER should be on 3rd or 6th Aug....cross fingers, follicles grow well otherwise it's going to get expensive if need to increase puregon dose.
Sunday, July 22, 2007
Am i doing too much?
Am i having too much on my plate at this point in time? going through IVF cycle is tough enough, having to work full time and trying to run a business and expanding, geting new manufacturers, having to do the housework etc etc...
i can't give up any of the above, already outsource the housework...work brings in money, business is sucking up money as fast as i could earn it. i really hope that it will work out in the end, if it does..i can quit and work from home and look after the pregnancy. worse case scenario ..if both doesn't work out, at least i have my work to fall back upon.
i can't give up any of the above, already outsource the housework...work brings in money, business is sucking up money as fast as i could earn it. i really hope that it will work out in the end, if it does..i can quit and work from home and look after the pregnancy. worse case scenario ..if both doesn't work out, at least i have my work to fall back upon.
Wednesday, July 18, 2007
Lucrin or Lupron as called in the US
Clinical Policy Bulletin:Gonadotropin-Releasing Hormone Analogs (Lupron/Zoladex) and Antagonists (Plenaxis)
Number: 0501
Policy
Lupron
Aetna considers Lupron (leuprolide) medically necessary for the following indications subject to the specified limitations:
Endometriosis (see appendix)
To decrease fibroid size prior to surgery (see appendix).
To decrease endometrial thickness prior to endometrial ablation (see appendix).
For palliative treatment of members with advanced (Stage III or Stage IV) prostate cancer that has metastasized or has recurred after treatment, or member refuses orchiectomy (see appendix).
For true (central) precocious puberty, defined as sexual maturation before age 8 in girls and age 10 in boys, and tumor has been ruled out by lab tests, CT, MRI, or ultrasound (see appendix).
Infertility (used in conjunction with urofollitropin or menotropins) to suppress luteinizing hormone (LH) production in members with documented premature LH surge, or used in “super-ovulation” regimens associated with in vitro fertilization (see appendix).
For treatment of metastatic breast cancer, when the member is pre-menopausal and the disease has progressed or recurred after a trial of at least 3 months of tamoxifen (see appendix).
To suppress onset of puberty in cases where the adolescent meets medical necessity criteria for growth hormone supplementation and has early onset of puberty and is not within target growth range (within 1 standard deviation of mean height for age and sex) (see appendix).
For the treatment of women with chronic refractory pelvic pain (see appendix).
Aetna considers Lupron experimental and investigational for all other indications, including any of the following conditions, since limited information has been published and further research including randomized, controlled trials is required to determine its efficacy:
Precocious pubarche alone, or pseudoprecocious puberty (gonadotropin independent precocious puberty); or
Polycystic ovarian disease; or
Pre-menstrual syndrome; or
Endometrial cance; or
Ovarian cancer; or
Preservation (suppression) of ovarian function during chemotherapy; or
Preservation (suppression) of testicular function during chemotherapy.
Zoladex
Aetna considers Zoladex (goserelin) medically necessary for any of the following indications:
Advanced (metastatic) prostatic carcinoma; or
Advanced (metastatic) breast cancer in pre-menopausal members; or
Endometriosis, Stage III or IV; or
Uterine fibroids (leiomyoma uteri) (preoperative adjunct to surgical treatment) (short-term (less than 6 months) use); or
Endometrial ablation or hysterectomy (preoperative adjunct) (short-term (less than 6 months) use). (See also CPB 091 - Endometrial Ablation.)
Aetna considers Zoladex (goserelin) experimental and investigational for preservation of ovarian or testicular function during chemotherapy and for all other indications because its effectiveness for these indications has not been established.
Plenaxis
Aetna considers Plenaxis (abarelix) medically necessary for the treatment of the symptoms of men with advanced prostate cancer who cannot take other hormone therapies and who have refused surgical castration. Abarelix is considered experimental and investigational for all other indications. This policy is based on the FDA-approved indications for Plenaxis.
For gonadotropin-releasing hormone antagonists for infertility, see CPB 327 - Infertility.
Background
Lupron:
Leuprolide (Lupron) is a gonadotropin-releasing hormone analog, which may be indicated for treatment of certain conditions, which are hormonally regulated.
Leuprolide may be indicated in advanced cancer (palliative treatment) in patients who have inoperable prostate tumor, or refuse orchiectomy. The available literature suggests combined therapy with leuprolide and an anti-androgen (e.g., megestrol, flutamide) appears to produce additive effects and to be more effective than leuprolide therapy alone in the treatment of advanced prostate cancer. According to established guidelines, recommended dosing of leuprolide for palliative treatment of advanced prostate cancer is 1 mg given subcutaneously daily. According to established guidelines, if patient is receiving leuprolide acetate suspension (Lupron depot) dosing is 7.5 mg IM once monthly.
Leuprolide has been used in the treatment of true (central) precocious puberty, defined as sexual maturation less than age 8 in girls, and sexual maturation less than age 10 in boys. The available literature suggests tumors should be ruled out by lab tests, CT, MRI, or ultrasound. Leuprolide is not indicated for precocious pubarche alone or pseudoprecocious puberty (gonadotropin-independent precocious puberty). According to established guidelines, recommended starting doses are: Lupron Depot Ped: 0.3 mg/kg every four weeks (minimum 7.5 mg), or Lupron injection: 50 mcg/kg daily. Doses may be titrated upwards in order to achieve hormonal down-regulation.
Studies of leuprolide for endometriosis indicate that six months is an appropriate length for therapy. Because of lack of safety data with long-term use, and because of concerns expressed in the available literature regarding effects on bone density, treatment after six months is typically not recommended. According to established guidelines, recommended dosing of leuprolide for endometriosis is 3.75 mg as a single monthly IM injection.
Leuprolide has been studied for the treatment of uterine fibroids (leiomyoma uteri), as a preoperative adjunct to surgical treatment. Clinical studies have demonstrated the benefit of leuprolide in reducing vascular and surgical complications secondary to obstructive fibroid size. In tests, GnRH agonists have effectively reduced the fibroid size, but their use was accompanied by a rapid regrowth following discontinuation. The available literature states Leuprolide therapy does not prevent or replace the eventual need for surgery. If used as a pre-operative adjunct, the available literature states short-term treatment only is recommended (i.e., 1-3 months).
Leuprolide also has been shown to be an effective preoperative adjunct to decrease endometrial thickness prior to endometrial ablation. If used as a pre-operative adjunct, short-term treatment only (i.e., 1-2 months) is indicated.
Leuprolide is used in conjunction with urofollitropin or menotropins in patients with infertility. It has been used to suppress LH production in patients with documented premature LH surge. In addition, it has been used in “super-ovulation” regimens associated with in vitro fertilization. Treatment of infertility may be subject to limitations under some benefit plans. Some HMO contracts, with or without a separate infertility benefit such as the Advanced Reproductive Technology (ART) Rider, specifically exclude injectable infertility drugs.
Leuprolide has been shown to be useful in the treatment of metastatic breast cancer in pre-menopausal patients whose disease has progressed or recurred despite a 3 or more month trial of tamoxifen.
Leuprolide has been used as treatment for various other conditions (e.g., polycystic ovarian disease, hypermenorrhea, premenstrual syndrome, paraphilias, endometrial cancer, and ovarian cancer). At this time limited information has been published to show efficacy for conditions other than those mentioned in the clinical criteria above. Further research with randomized, controlled trials is required to determine efficacy in these other conditions.
The American Society of Clinical Oncology's recommendations on fertility preservation in cancer patients (Lee, et al., 2006) stated that sperm and embryo cryopreservation are considered standard practice. On the other hand, the use of GNRH analogs or antagonists for testicular or ovarian suppression is considered investigational. ASCO guidelines state: “At this time, since there is insufficient evidence regarding the safety and effectiveness of GnRH analogs and other means of ovarian suppression on female fertility preservation, women interested in ovarian suppression for this purpose are encouraged to participate in clinical trials.” The guidelines also noted that there is insufficient evidence of the effectiveness of GnRH analogues in preventing chemotherapy-induced gonadal damage in men: “The efficacy of gonadoprotection through hormonal manipulations has only been evaluated in very small studies in cancer patients.”
In a review of the literature, Sonmezer and Oktay (2006) explained that there are a limited number of prospective studies of GNRH analogues in preventing chemotherapy-induced gonadal damage, “which are flawed because of short-term follow-up and/or because of lack of control subjects.” The review notes that “[i]n addition to the lack of consistent support from clinical studies, there is currently no biological explanation for who GNRHa [GNRH analogues] can affect ovarian reserve.” The authors concluded that “[i]n the absence of a prospective randomized study with sufficient power, we do not rely on ovarian suppression as an effective means of fertility preservation.”
Zoladex:
Goserelin (Zoladex) is a gonadotropin releasing hormone (GnRH) (also known as gonadorelin and luteinizing hormone releasing hormone or LHRH) analog, which is indicated in certain conditions requiring suppression of estrogen or testosterone secretion. At this time it is available only in a continuous-release subcutaneous implant which releases drug over a period of about 28 days.
Goserelin is approved by the FDA for treatment of advanced metastatic prostate cancer and advanced endometriosis. Goserelin has also been shown to be effective for treatment or palliation of breast cancer in pre-menopausal patients.
Goserelin has been studied for the treatment of uterine fibroids. Clinical studies have demonstrated the benefit of leuprolide in reducing vascular and surgical complications secondary to obstructive fibroid size. In tests, GnRH agonists have effectively reduced the fibroid size, but their use was accompanied by a rapid regrowth following discontinuation. Therefore, the literature states that goserelin therapy does not prevent or replace the eventual need for surgery. If used as a pre-operative adjunct, the literature recommends short-term treatment (six months or less).
Goserelin has been shown to be effective for the short-term (less than 6 months) preoperative adjunct to endometrial ablation or surgery for leiomyomata uteri (uterine fibroids).
Goserelin is under investigation as a method of prevention of chemotherapy-induced gonadal damage. In a prospective pilot study (n = 5), Franke, et al. (2005) explore the effects of goserelin acetate in women with Hodgkin's disease (HD) receiving chemotherapy while taking a continuous combined estrogen-progestin preparation as add-back on the prevention of premature ovarian failure (POF). Pre-menopausal women with HD received goserelin and add-back until polychemotherapy was completed. Every 4 weeks during treatment and thereafter, a hormonal profile (follicle-stimulating hormone (FSH), LH, 17beta-estradiol, progesterone and inhibin B) was measured until resumption of menstruation or the development of a hyper-gonadotropic state (2 x FSH greater than 30 U/l). All patients reached pre-pubertal status during treatment. Following cessation of goserelin therapy, 1 patient developed a hyper-gonadotropic state and 4 patients resumed menstruation. One of those patients became pregnant and delivered a healthy son. These investigators concluded that the effectiveness of GnRH agonist plus add-back on the prevention of POF during polychemotherapy in women with HD needs further elucidation in randomized controlled trials.
Del Mastro, et al. (2006) noted that standard methods to prevent chemotherapy-induced early menopause in young, breast cancer patients are unavailable to date. Pre-clinical data has suggested that LHRH analogs given during treatment can decrease the gonado-toxicity induced by chemotherapy. In a phase II clinical trial, these investigators evaluated the activity of such a method in young, breast cancer patients undergoing adjuvant chemotherapy. Pre-menopausal patients received goserelin 3.6 mg every 4 weeks before and during chemotherapy. According to 2-stage optimal phase II Simon design, treatment was considered clinically interesting if it was able to prevent menopause in 19 out of 29 patients of the study population. The resumption of ovarian function was defined by a resumption of menstrual activity or by a FSH value less than or equal to 40 IU/l within 12 months after the last cycle of chemotherapy. A total of 30 patients were enrolled and 29 were evaluable. Median age was 38 years (range 29 to 47 years). All but one patient received CEF regimen (cyclophosphamide, epirubicin, 5-fluorouracil). Resumption of menstrual activity was observed in 21 patients (72%; 95% CI 52 to 87%) and a FSH value less than or equal to 40 IU/l in 24 patients (83%; 95% CI 63 to 93%). Menses resumption was observed in 16 out of 17 patients (94%) with age less than 40 years and in 5 out of 12 patients (42 %) with age 40 years or over. These researchers concluded that goserelin given before and during chemotherapy may prevent premature menopause in the majority of patients. However, the different success rate by age indicates the need of a prospective evidence of the effectiveness of such a strategy.
Plenaxis:
Plenaxis (abarelix) is a gonadotropin-releasing hormone antagonist approved by the FDA in November 2003. It is indicated for the treatment of the symptoms of men with advanced prostate cancer who cannot take other hormone therapies and who have refused surgical castration. Plenaxis is marketed under a voluntary risk management program agreed to and administered by the sponsor that will restrict the use of Plenaxis to patients with advanced prostate cancer, who have no alternative therapy, because of an increased risk of serious, and potentially life-threatening, allergic reactions associated with its use.
In a phase III clinical study (n = 269), McLeod et al (2001) evaluated the levels of testosterone and other hormones in men with prostate cancer treated with abarelix versus leuprolide acetate. The authors concluded that treatment with abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, LH, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.
In another phase III clinical trial (n = 255), Trachtenberg et al (2002) reported that abarelix as monotherapy achieved medical castration significantly more rapidly than combination therapy (LHRH agonist and a non-steroidal anti-androgen) and avoided the testosterone surge characteristic of agonist therapy. Both treatments were equally effective in reducing serum prostate specific antigen, and achieving and maintaining castrate levels of testosterone.
Koch, et al. (2003) stated that abarelix provided a safe and effective medical alternative to surgical castration in symptomatic patients (n = 81) with advanced prostate cancer without the risk of the clinical flare associated with LHRH agonists.
Appendix
Medically Necessary Indications for Lupron
Limitations
Endometriosis
Up to six months - because of lack of safety data with long-term use, and concerns in available peer-reviewed medical literature regarding effects on bone density.
Lupron dosages greater than 3.75 mg per month or 11.25 mg per 3 months are subject to medical necessity review.
To decrease fibroid size prior to surgery
Up to three months - under accepted guidelines, does not prevent or replace the eventual need for surgery except in peri-menopausal women.
Lupron dosages greater than 3.75 mg per month or 11.25 mg per 3 months are subject to medical necessity review.
To decrease endometrial thickness prior to endometrial ablation
Up to two months.
Lupron dosages greater than 3.75 mg per month or 11.25 mg per 3 months are subject to medical necessity review.
For palliative treatment in members with advanced prostate cancer, defined as Stage III or Stage IV, that has metastasized or recurred after treatment, or patient refuses orchiectomy
1 mg given subcutaneously daily. If receiving leuprolide acetate suspension (Lupron Depot), dosing is 7.5 mg IM once monthly.
For true (central) precocious puberty, defined as sexual maturation before age 8 in girls and age 10 in boys, and tumor has been ruled out by lab tests, CT, MRI, or ultrasound
Lupron Depot Ped: 0.3 mg/kg every four weeks (minimum 7.5 mg).
Lupron injection: 50 mcg/kg daily. It may be medically necessary to titrate dosages upwards in order to achieve hormonal down-regulation.
Infertility (used in conjunction with urofollitropin or menotropins) to suppress luteinizing hormone (LH) production in members with documented premature LH surge, or used in “super-ovulation” regimens associated with in vitro fertilization
Note: Treatment of infertility may be subject to specific limitations under some benefit plans. Most HMO plans exclude injectable infertility drugs from coverage.
For treatment of metastatic breast cancer
Indicated where member is pre-menopausal and the disease has progressed or recurred after a trial of at least 3 months of tamoxifen
To suppress onset of puberty in adolescents with early onset of puberty on growth hormone therapy
Adolescent must meet medical necessity criteria for growth hormone supplementation, have early onset of puberty, and be below target growth range (within 1 standard deviation of mean height for age and sex)
For the treatment of women with chronic refractory pelvic pain
Indicated where attempts at medical therapy with analgesics and oral contraceptive have been unsuccessful.
CPT Codes / HCPCS Codes / ICD-9 Codes
Lupron (suspension and implant):
HCPCS codes covered if selection criteria are met:
J1950
Injection leuprolide acetate (for depot suspension), per 3.75 mg
J9217
Leuprolide acetate (for depot suspension), 7.5 mg
J9219
Leuprolide acetate implant, 65 mg
ICD-9 codes covered if selection criteria are met:
174.0 - 175.9
Malignant neoplasm of breast
185
Malignant neoplasm of prostate
218.0 - 218.9
Uterine leiomyoma
233.0
Carcinoma in situ of breast
233.4
Carcinoma in situ of prostate
259.1
Precocious sexual development and puberty, not elsewhere classified
617.0 - 617.9
Endometriosis
Lupron prior to endometrial ablation (see CPB 91):
ICD-9 codes covered if selection criteria are met:
626.2
Excessive or frequent menstruation
626.3
Puberty bleeding
627.0
Premenopausal menorrhagia
627.1
Postmenopausal bleeding
2 week Lupron kit:
HCPCS codes covered if selection criteria are met:
J9218
Leuprolide acetate, per 1 mg
Other HCPCS codes related to the CPB:
J3355
Injection, urofollitropin, 75 IU
S0122
Injection, menotropins, 75 IU
S0187
Tamoxifen citrate, oral, 10 mg
ICD-9 codes covered if selection criteria are met:
185
Malignant neoplasm of prostate
233.4
Carcinoma in situ of prostate
259.1
Precocious sexual development and puberty, not elsewhere classified
628.0 - 628.9
Infertility, female
ICD-9 codes not covered for indications listed in the CPB:
140.0 - 239.9
Neoplasms [when used for preservation of ovarian or testicular function during chemotherapy]
182.0
Malignant neoplasm of corpus uteri, except isthmus
183.0
Malignant neoplasm of ovary
198.6
Secondary malignant neoplasm of ovary
218.0 - 218.9
Uterine leiomyoma
256.4
Polycystic ovaries
625.4
Premenstrual tension syndromes
V58.11 - V58.12
Encounter for antineoplastic chemotherapy and immunotherapy [when used for preservation of ovarian or testicular function during chemotherapy]
Zoladex (Goserelin):
HCPCS codes covered if selection criteria are met:
J9202
Goserelin acetate implant, per 3.6 mg
ICD-9 codes covered if selection criteria are met:
174.0 - 175.9
Malignant neoplasm of breast
185
Malignant neoplasm of prostate
218.0 - 218.9
Uterine leiomyoma
233.0
Carcinoma in situ of breast
233.4
Carcinoma in situ of prostate
617.0 - 617.9
Endometriosis
625.3
Dysmenorrhea
628.0 - 628.9
Infertility, female
Zoladex prior to endometrial ablation (see CPB 91):
ICD-9 codes covered if selection criteria are met:
626.2
Excessive or frequent menstruation
626.3
Puberty bleeding
627.0
Premenopausal menorrhagia
627.1
Postmenopausal bleeding
ICD-9 codes not covered for indications listed in the CPB:
140.0 - 239.9
Neoplasms [when used for preservation of ovarian or testicular function during chemotherapy]
V58.11 - V58.12
Encounter for antineoplastic chemotherapy and immunotherapy [when used for preservation of ovarian or testicular function during chemotherapy]
Plenaxis (abarelix):
Other CPT codes related to the CPB:
54520 - 54535, 54690
HCPCS codes covered if selection criteria are met:
C9216
Injection, Abarelix for injectable suspension, per 10 mg (deleted 12-31-04)
J0128
Injection, abarelix, 10 mg
ICD-9 codes covered if selection criteria are met:
185
Malignant neoplasm of prostate
Other ICD-9 codes related to the CPB for Lupron, Zoladex, and Plenaxis:
253.3
Pituitary dwarfism
625.8 - 625.9
Other and unspecified symptoms associated with female genital organs
V58.11 - V58.12
Encounter for antineoplastic chemotherapy and immunotherapy
V66.0
Convalescence and palliative care following surgery
V66.1
Convalescence and palliative care following radiotherapy
V66.2
Convalescence and palliative care following chemotherapy
V66.7
Encounter for palliative care The above policy is based on the following references:
Lupron:
Olin BR, ed. Drug Facts and Comparisons. St. Louis, MO: JB Lippincott Company; 1992.
Conn MP, Crowley WF. Gonadotropin-releasing hormone and its analogues. N Engl J Med. 1991;324(2):93-103.
Higham JM. The medical management of menorrhagia. Br J Hosp Med. 1991;45:19-21.
Schriock ED. Practical aspects of pulsatile gonadotropin-releasing hormone administration. Am J Obstet Gynecol. 1990;163(5):1765-1770.
Gompel A, Mauvais-Jarvis P. Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea. Hum Reprod. 1988;3(4):473-477.
Macdonald R. Modern treatment of menorrhagia. Br J Obstet Gynecol. 1990;97:3-7.
Dodson WC, Hughes CL, Whitesides DB, et al. The effect of leuprolide acetate on ovulation induction with human menopausal gonadotropins in polycystic ovary syndrome. J Endocrin Metab. 1987;65(1):95-100.
Adamson GD. Treatment of uterine fibroids: Current findings with gonadotropin-releasing hormone agonists. Am J Obstet Gynecol. 1992;166(2):746-751.
Brooks PG, Serden SP. Preparation of the endometrium for ablation with a single dose of leuprolide acetate depot. J Reprod Med. 1991;36(7):477-478.
Shaw RW, Fraser HM. Use of a superactive luteinizing hormone releasing hormone agonist in the treatment of menorrhagia. Br J Obstet Gynecol. 1984;91:913-916.
Schrlock ED. GnRH agonists. Clin Obstet Gynecol. 1989;32(3):550-563.
Hodgen GD. General applications of GnRH agonists in gynecology: Past, present and future. Obstet Gynecol Surv. 1989;44(5):293-296.
McEvoy GK, ed. American Hospital Formulary Service Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1992.
Bennett DR, ed. AMA Drug Evaluations Subscription. Chicago, IL: American Medical Association; Winter 1992.
Schrlock ED. GnRH agonists. Clin Obstet Gynecol. 1989;32(3):550-563.
Bucci KK, Carson DS. Contraception and infertility. In: Pharmacotherapy: A Pathophysiological Approach. JT Dipiro, RL Talbert, PE Hayes, et al, eds. Norwalk, CT: Appleton & Lange; 1993:1211-1130.
U.S. Pharmacopeial Convention, Inc. (USPC). USP Dispensing Information. Volume I -- Drug Information for the Healthcare Professional. 18th ed. Rockville, MD: USPC; 1998.
Medical Economics, Inc. Physicians' Desk Reference. 52nd ed. Montvale, NJ: Medical Economics Data Production; 1998.
Mosby-Year Book, Inc. Mosby's GenRx: The Complete Reference for Generic and Brand Drugs. 8th ed. St. Louis, MO: Mosby; 1998.
American Hospital Formulary Service (AHFS). AHFS Drug Information 98. Bethesda, MD: American Society of Health-System Pharmacists; 1998.
Levitsky AM. Pharmacologic treatment of hypersexuality and paraphilias in nursing home residents. J Am Geriatr Soc. 1999;47(2):231-234.
Vilos GA, Lefebvre G, Graves GR, et al. Guidelines for the management of abnormal uterine bleeding. SOCG Clinical Practice Guidelines No. 106. J Obstet Gynaecol Can. 2001;23(8):704-709.
Duckitt K. Menorrhagia. In: Clinical Evidence, Issue 9. London, UK: BMJ Publishing Group, Ltd.; June 2003.
Lethaby A, Hickey M. Endometrial destruction techniques for heavy menstrual bleeding. Cochrane Database Syst Rev. 2002;(2):CD001501.
Sowter MC, Lethaby A, Singla AA. Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev. 2002;(3):CD001124.
Rao GG, Miller DS. Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006;6(1):43-47.
Lee SJ, Schover LR, Partridge AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24(18):2917-2931.
Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy. Oncologist. 2006;11(5):422-434.
Precocious Puberty
Brenner PE. Precocious puberty in the female. In: Reproductive Endocrinology, Infertility and Contraception. DR Mishell, VC Davajan, eds. Philadelphia, PA: FA Davis Co.; 1979.
Partsch CJ, Sippell WG. Treatment of central precocious puberty. Best Pract Res Clin Endocrinol Metab. 2002;16(1):165-189.
Mul D, Wit JM, Oostdijk W, et al. The effect of pubertal delay by GnRH agonist in GH-deficient children on final height. J Clin Endocrinol Metab. 2001;86(10):4655-4656.
Cara JF, Kreiter ML, Rosenfield RL. Height prognosis of children with true precocious puberty and growth hormone deficiency: Effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone. J Pediatr. 1992;120(5):709-715.
Pelvic Pain
ACOG Committee on Practice Bulletins -- Gynecology. ACOG Practice Bulletin No. 51. Chronic pelvic pain. Obstet Gynecol. 2004;103(3):589-605.
Royal College of Obstetricians and Gynaecologists (RCOG). The initial management of chronic pelvic pain. RCOG Guideline No. 41. London, UK: RCOG; April 2005.
Infertility
Albuquerque LE, Saconato H, Maciel MC. Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles. Cochrane Database Syst Rev. 2005;(1):CD002808.
Al-Inany H, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev. 2001;(4):CD001750.
Nugent D, Vandekerckhove P, Hughes E, et al. Gonadotrophin therapy for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev. 2000;(3):CD000410.
Prostate cancer
Wojciechowski NJ, Carter CA, Skoutakis VA, et al. Leuprolide: A gonadotropin-releasing hormone analog for the palliative treatment of prostate cancer. Drug Intell Clin Pharm. 1986;20:746-751.
Debruyne F. Hormonal therapy of prostate cancer. Semin Urol Oncol. 2002;20(3 Suppl 1):4-9.
National Institutes of Health. The management of clinically localized prostate cancer. National Institutes of Health Consensus Development Conference 1987 June 15-17. NCI Monogr. 1988;(7):1-174.
Seidenfeld J, Samson DJ, Aronson N, et al. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer. Evidence Report/Technology Assessment No. 4. Prepared for the Agency for Healthcare Policy and Research (AHCPR) by the Blue Cross and Blue Shield Association Technology Evaluation Center. AHCPR Pub. No. 99-E0021. Rockville, MD: AHCPR; May 1999.
Seidenfeld J, Samson DJ, Hasselblad V, et al. Single-therapy androgen suppression in men with advanced prostate cancer: A systematic review and meta-analysis. Ann Intern Med, 2000;132(7):566-577.
Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: An overview of the randomised trials. Lancet, 2000;355:1491-1498.
Wilt T, Nair B, MacDonald R, Rutks I. Early versus deferred androgen suppression in the treatment of advanced prostatic cancer. Cochrane Database Syst Rev. 2001;(4):CD003506.
Schmitt B, Bennett C, Seidenfeld J, et al. Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev. 1999;(2):CD001526.
Leiomyomas
Lefebvre G, Vilos G, Allaire C, et al. The management of uterine leiomyomas. SOGC Clinical Practice Guidelines. No. 128. Society of Obstetricians and Gynaecologists of Canada. J Obstet Gynaecol Can. 2003;25(5):396-405.
Vollenhoven BJ. Uterine fibroids: A clinical review. Br J Obstet Gynecol. 1990;97:285-298.
Friedman AJ. Treatment of leiomyomata uteri with short-term leuprolide followed by leuprolide plus estrogen-progestin hormone replacement therapy for 2 years: A pilot study. Fertil Steril. 1988;51(3):526-528.
Farquhar C, Arroll B, Ekeroma A, et al. An evidence-based guideline for the management of uterine fibroids. Working Party of the New Zealand Guidelines Group. New Zealand Guidelines Group; November 1999.
Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2001;(2):CD000547.
Breast cancer
Olin BR. Drug Facts and Comparisons. St. Louis, MO: J.B. Lippincott Company; 1992.
McEvoy GK, ed. Leuprolide. In: AHFS Drug Information. Bethesda, MD: American Society of Hospital Pharmacists; 1993:606-612.
McGuire T. Breast cancer. In: Pharmacotherapy: A Pathophysiologic Approach. 2nd ed. J Dipiro, RL Talbert, PE Hayes, et al, eds. Norwalk, CT: Appleton & Lange; 1993:1930-1945.
Dowsett M, Jacobs S, Aherne J, et al. Clinical and endocrine effects of leuprorelin acetate in pre- and postmenopausal patients with advanced breast cancer. Clin Ther. 1992;14 Suppl A:97-103.
Manni A, Santen R, Harvey H, et al. Treatment of breast cancer with gonadotropin-releasing hormone. Endocr Rev. 1986;7(1):89-94.
Harvey HA, Lipton A, Max DT, et al. Medical castration produced by the GNRH analogue leuprolide to treat metastatic breast cancer. J Clin Oncol. 1985;3(8):1068-1072.
Sunderland MC, Osborne CK. Tamoxifen in premenopausal patients with metastatic breast cancer: A review. J Clin Oncol. 1991;9(7):1283-1297.
No authors listed. Tamoxifen. In: Drug Evaluation Subscriptions. DR Bennett, ed. Chicago, IL: American Medical Association; 1993;5:5.
Endometriosis
Henzl MR, Corson SL, Moghissi K, et al. Administration of nasal nafarelin as compared with oral danazol for endometriosis. N Engl J Med. 1988;318(8):485-489.
Letassy NA, Thompson DF, Britton ML, et al. Nafarelin acetate: A gonadotropin-releasing hormone agonist for the treatment of endometriosis. DICP. 1990;24:1204-1209.
Lemay A, Maheux R, Quesnel G, et al. LH-RH agonist treatment of endometriosis. Contr Gynec Obstet. 1987;16:247-253.
Souney PF, Rossiter A. Focus on naferelin acetate: GnRH agonist for the management of endometriosis. Hosp Formul. 1990;25:1041-1054..
Wheeler JM, Knittle JD, Miller JD. Depot leuprolide versus danazol in the treatment of women with symptomatic endometriosis. Am J Obstet Gynecol. 1992;167(1):283-291.
Gerhard I, Schindler AE, Bruhler K, et al. Treatment of endometriosis with leuprorelin acetate dept: A German multicenter study. Clin Ther.1992;14(Suppl A):3-16.
Crosignani PG, Gastaldi A, Lombardi PL, et al. Leuprorelin acetate depot versus danazol in the treatment of endometriosis: Results of an open multicenter trial. Clin Ther. 1992;14 (Suppl A):29-36.
Tummon IS, Pepping ME, Binor Z, et al. A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis. Fertil Steril. 1989;51(3):390-394.
Fayez JA, Collazo LM, Vernon C. Comparison of different modalities of treatment for minimal and mild endometriosis. Am J Obstet Gynecol. 1988;159:927-932.
Moghissi KS, Hull ME, Magyar DM, et al. Comparison of different treatment modalities of endometriosis in infertile women. Controversies Gyncec Obstet. 1987;16:236-240.
Olive DL, Schwartz LB. Endometriosis. New Engl J Med. 1993;328(24):1759-1767.
Saltiel E, Garabedian-Ruffal SM. Pharmacologic management of endometriosis. Clin Pharm. 1991;10:518-531.
Olin BR. Drug Facts and Comparisons. St. Louis, MO: JB Lippincott Company; 1992.
Schmidt CL. Endometriosis: A reappraisal of pathogenesis and treatment. Fertil Steril. 1985;44(2):157-173.
Buckman RW. Endometriosis: Pharmacologic alternatives to surgery. J Pract Nurs. 1994;44(3):47-56.
Rebar RW. The ovaries. In: Cecil Textbook of Medicine. 19th ed. JB Wyngaarden, LH Smith, JC Bennett, eds. Philadelphia, PA: WB Saunders Co.; 1992.
Segraves R, Letassy NA. Gynecologic disorders. In: Applied Therapeutics. 5th ed. MA Koda-Kimble, LY Young, eds. Vancouver, BC: Applied Therapeutics, Inc.; 1992:70-77.
Winkel CA, Scialli AR. Medical and surgical therapies for pain associated with endometriosis. J Womens Health Gend Based Med. 2001;10(2):137-162.
Howard FM. An evidence-based medicine approach to the treatment of endometriosis-associated chronic pelvic pain: Placebo-controlled studies. J Am Assoc Gynecol Laparosc, 2000;7(4):477-488.
Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev. 2004;(3):CD003678.
Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev. 2003;(3):CD000155.
Premenstrual syndrome
Hussain SY, Massil JH, Matta WH, et al. Buserelin in premenstrual syndrome. Gynecol Endocrinol. 1992;6(1):57-64.
Blackstrom T, Hammarback S. Premenstrual syndrome--psychiatric or gynaecological disorder? Ann Med. 1991;23(6):625-633.
Mortola JF, Girton L, Fischer U. Successful treatment of severe premenstrual syndrome by combined use of gonadotropin-releasing hormone agonist and estrogen/progestin. J Clin Endocrinol Metab. 1991;72(2):252A-252F.
Hammarback S, Backstrom T. Induced anovulation as treatment of premenstrual tension syndrome. A double-blind cross-over study with GnRH-agonist versus placebo. Acta Obstet Gynecol Scand. 1988;67(2):159-166.
Bancroft J, Boyle H, Warner P, et al. The use of an LHRH agonist, buserelin, in the long-term management of premenstrual syndromes. Clin Endocrinol (Oxf). 1987;27(2):171-182.
Muse KN, Cetel NS, Futterman LA, et al. The premenstrual syndrome. Effects of 'medical ovariectomy'. N Engl J Med. 1984;311(21):1345-1349.
Zoladex
No authors listed. Endocrine drugs: Drugs used for gynecologic indications. In: Drug Evaluations Subscription. DR Bennett, ed. Chicago, IL: American Medical Association; 1993; II/ENDO-6:11-12.
No authors listed. Oncolytic drugs: Antineoplastic agents: Hormonal agents. In: Drug Evaluations Subscription. DR Bennett, ed. Chicago, IL: American Medical Association; 1993; III/ONC-5:12-15.
United States Pharmacopeial Convention, Inc. (USPC). Goserelin (Systemic). In: USP Dispensing Iinformation. Volume 1 - Drug Information for the Healthcare Professional, 15th ed. Rockville, MD:,USPC; 1995:1410-1411.
United States Pharmacopeial Convention, Inc. (USPC). Additional products and indications In: USP Dispensing Information. Volume 1 - Drug Information for the Healthcare Professional. 15th ed. Rockville, MD: USPC; 1995:2849.
Lu PY, Ory SJ. Endometriosis: Current management. Mayo Clin Proc. 1995;70:453-463.
Goldhirsch A, Wood WC, Senn HJ, et al. Meeting highlights: International consensus panel on the treatment of primary breast cancer (commentary). J Natl Cancer Inst. 1995;87(19):1441-1445.
Vercellini P, Fedele L, Maggi R, et al. Gonadotropin releasing hormone agonist for chronic anovulatory uterine bleeding and severe anemia. J Reprod Med. 1993;38(2):127-129.
DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 4th ed. Philadelphia, PA: JB Lippincott Co.; 1993.
United States Pharmacopeial Convention, Inc (USPC). USP Dispensing Information. Volume I -- Drug Information for the Health Care Professional. Rockville, MD: USPC; 1998.
American Society of Health-System Pharmacists, Inc. American Hospital Formulary Service Drug Information 98. Bethesda, MD: American Society of Health-System Pharmacists; 1998.
Medical Economics, Inc. Physicians' Desk Reference. 52nd ed. Montvale, NJ: Medical Economics; 1998.
Mosby-Year Book, Inc. Mosby's GenRx: The Complete Reference for Generic and Brand Drugs, 8th ed. St. Louis, MO: Mosby; 1998.
Korman LB. Treatment of prostate cancer. Clin Pharm. 1989;8:412-424.
Furr BA, Woodburn JR. Luteinizing hormone-releasing hormone and its analogues: A review of biological properties and clinical uses. J Endocrinol Invest. 1988;11:535-537.
Hughes E, Collins J, Vandekerckhove P. Gonadotropin releasing hormone analogue as an adjunct to gonadotropin therapy for clomiphene-resistant PCOS. Cochrane Database of Systematic Reviews. Oxford, U.K.: Update Software; 1998.
Franke HR, Smit WM, Vermes I. Gonadal protection by a gonadotropin-releasing hormone agonist depot in young women with Hodgkin's disease undergoing chemotherapy. Gynecol Endocrinol. 2005;20(5):274-278.
Del Mastro L, Catzeddu T, Boni L, et al. Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients. Ann Oncol. 2006;17(1):74-78.
Plenaxis
Cook T, Sheridan WP. Development of GnRH antagonists for prostate cancer: New approaches to treatment. Oncologist. 2000;5(2):162-168.
McLeod D, Zinner N, Tomera K, et al. A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology. 2001;58(5):756-761.
Trachtenberg J, Gittleman M, Steidle C, et al. A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J Urol. 2002;167(4):1670-1674.
Koch M, Steidle C, Brosman S, et al. An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists. Urology. 2003;62(5):877-882.
Reddy GK. Abarelix (Plenaxis): A gonadotropin-releasing hormone antagonist for medical castration in patients with advanced prostate cancer. Clin Prostate Cancer. 2004;2(4):209-211.
Number: 0501
Policy
Lupron
Aetna considers Lupron (leuprolide) medically necessary for the following indications subject to the specified limitations:
Endometriosis (see appendix)
To decrease fibroid size prior to surgery (see appendix).
To decrease endometrial thickness prior to endometrial ablation (see appendix).
For palliative treatment of members with advanced (Stage III or Stage IV) prostate cancer that has metastasized or has recurred after treatment, or member refuses orchiectomy (see appendix).
For true (central) precocious puberty, defined as sexual maturation before age 8 in girls and age 10 in boys, and tumor has been ruled out by lab tests, CT, MRI, or ultrasound (see appendix).
Infertility (used in conjunction with urofollitropin or menotropins) to suppress luteinizing hormone (LH) production in members with documented premature LH surge, or used in “super-ovulation” regimens associated with in vitro fertilization (see appendix).
For treatment of metastatic breast cancer, when the member is pre-menopausal and the disease has progressed or recurred after a trial of at least 3 months of tamoxifen (see appendix).
To suppress onset of puberty in cases where the adolescent meets medical necessity criteria for growth hormone supplementation and has early onset of puberty and is not within target growth range (within 1 standard deviation of mean height for age and sex) (see appendix).
For the treatment of women with chronic refractory pelvic pain (see appendix).
Aetna considers Lupron experimental and investigational for all other indications, including any of the following conditions, since limited information has been published and further research including randomized, controlled trials is required to determine its efficacy:
Precocious pubarche alone, or pseudoprecocious puberty (gonadotropin independent precocious puberty); or
Polycystic ovarian disease; or
Pre-menstrual syndrome; or
Endometrial cance; or
Ovarian cancer; or
Preservation (suppression) of ovarian function during chemotherapy; or
Preservation (suppression) of testicular function during chemotherapy.
Zoladex
Aetna considers Zoladex (goserelin) medically necessary for any of the following indications:
Advanced (metastatic) prostatic carcinoma; or
Advanced (metastatic) breast cancer in pre-menopausal members; or
Endometriosis, Stage III or IV; or
Uterine fibroids (leiomyoma uteri) (preoperative adjunct to surgical treatment) (short-term (less than 6 months) use); or
Endometrial ablation or hysterectomy (preoperative adjunct) (short-term (less than 6 months) use). (See also CPB 091 - Endometrial Ablation.)
Aetna considers Zoladex (goserelin) experimental and investigational for preservation of ovarian or testicular function during chemotherapy and for all other indications because its effectiveness for these indications has not been established.
Plenaxis
Aetna considers Plenaxis (abarelix) medically necessary for the treatment of the symptoms of men with advanced prostate cancer who cannot take other hormone therapies and who have refused surgical castration. Abarelix is considered experimental and investigational for all other indications. This policy is based on the FDA-approved indications for Plenaxis.
For gonadotropin-releasing hormone antagonists for infertility, see CPB 327 - Infertility.
Background
Lupron:
Leuprolide (Lupron) is a gonadotropin-releasing hormone analog, which may be indicated for treatment of certain conditions, which are hormonally regulated.
Leuprolide may be indicated in advanced cancer (palliative treatment) in patients who have inoperable prostate tumor, or refuse orchiectomy. The available literature suggests combined therapy with leuprolide and an anti-androgen (e.g., megestrol, flutamide) appears to produce additive effects and to be more effective than leuprolide therapy alone in the treatment of advanced prostate cancer. According to established guidelines, recommended dosing of leuprolide for palliative treatment of advanced prostate cancer is 1 mg given subcutaneously daily. According to established guidelines, if patient is receiving leuprolide acetate suspension (Lupron depot) dosing is 7.5 mg IM once monthly.
Leuprolide has been used in the treatment of true (central) precocious puberty, defined as sexual maturation less than age 8 in girls, and sexual maturation less than age 10 in boys. The available literature suggests tumors should be ruled out by lab tests, CT, MRI, or ultrasound. Leuprolide is not indicated for precocious pubarche alone or pseudoprecocious puberty (gonadotropin-independent precocious puberty). According to established guidelines, recommended starting doses are: Lupron Depot Ped: 0.3 mg/kg every four weeks (minimum 7.5 mg), or Lupron injection: 50 mcg/kg daily. Doses may be titrated upwards in order to achieve hormonal down-regulation.
Studies of leuprolide for endometriosis indicate that six months is an appropriate length for therapy. Because of lack of safety data with long-term use, and because of concerns expressed in the available literature regarding effects on bone density, treatment after six months is typically not recommended. According to established guidelines, recommended dosing of leuprolide for endometriosis is 3.75 mg as a single monthly IM injection.
Leuprolide has been studied for the treatment of uterine fibroids (leiomyoma uteri), as a preoperative adjunct to surgical treatment. Clinical studies have demonstrated the benefit of leuprolide in reducing vascular and surgical complications secondary to obstructive fibroid size. In tests, GnRH agonists have effectively reduced the fibroid size, but their use was accompanied by a rapid regrowth following discontinuation. The available literature states Leuprolide therapy does not prevent or replace the eventual need for surgery. If used as a pre-operative adjunct, the available literature states short-term treatment only is recommended (i.e., 1-3 months).
Leuprolide also has been shown to be an effective preoperative adjunct to decrease endometrial thickness prior to endometrial ablation. If used as a pre-operative adjunct, short-term treatment only (i.e., 1-2 months) is indicated.
Leuprolide is used in conjunction with urofollitropin or menotropins in patients with infertility. It has been used to suppress LH production in patients with documented premature LH surge. In addition, it has been used in “super-ovulation” regimens associated with in vitro fertilization. Treatment of infertility may be subject to limitations under some benefit plans. Some HMO contracts, with or without a separate infertility benefit such as the Advanced Reproductive Technology (ART) Rider, specifically exclude injectable infertility drugs.
Leuprolide has been shown to be useful in the treatment of metastatic breast cancer in pre-menopausal patients whose disease has progressed or recurred despite a 3 or more month trial of tamoxifen.
Leuprolide has been used as treatment for various other conditions (e.g., polycystic ovarian disease, hypermenorrhea, premenstrual syndrome, paraphilias, endometrial cancer, and ovarian cancer). At this time limited information has been published to show efficacy for conditions other than those mentioned in the clinical criteria above. Further research with randomized, controlled trials is required to determine efficacy in these other conditions.
The American Society of Clinical Oncology's recommendations on fertility preservation in cancer patients (Lee, et al., 2006) stated that sperm and embryo cryopreservation are considered standard practice. On the other hand, the use of GNRH analogs or antagonists for testicular or ovarian suppression is considered investigational. ASCO guidelines state: “At this time, since there is insufficient evidence regarding the safety and effectiveness of GnRH analogs and other means of ovarian suppression on female fertility preservation, women interested in ovarian suppression for this purpose are encouraged to participate in clinical trials.” The guidelines also noted that there is insufficient evidence of the effectiveness of GnRH analogues in preventing chemotherapy-induced gonadal damage in men: “The efficacy of gonadoprotection through hormonal manipulations has only been evaluated in very small studies in cancer patients.”
In a review of the literature, Sonmezer and Oktay (2006) explained that there are a limited number of prospective studies of GNRH analogues in preventing chemotherapy-induced gonadal damage, “which are flawed because of short-term follow-up and/or because of lack of control subjects.” The review notes that “[i]n addition to the lack of consistent support from clinical studies, there is currently no biological explanation for who GNRHa [GNRH analogues] can affect ovarian reserve.” The authors concluded that “[i]n the absence of a prospective randomized study with sufficient power, we do not rely on ovarian suppression as an effective means of fertility preservation.”
Zoladex:
Goserelin (Zoladex) is a gonadotropin releasing hormone (GnRH) (also known as gonadorelin and luteinizing hormone releasing hormone or LHRH) analog, which is indicated in certain conditions requiring suppression of estrogen or testosterone secretion. At this time it is available only in a continuous-release subcutaneous implant which releases drug over a period of about 28 days.
Goserelin is approved by the FDA for treatment of advanced metastatic prostate cancer and advanced endometriosis. Goserelin has also been shown to be effective for treatment or palliation of breast cancer in pre-menopausal patients.
Goserelin has been studied for the treatment of uterine fibroids. Clinical studies have demonstrated the benefit of leuprolide in reducing vascular and surgical complications secondary to obstructive fibroid size. In tests, GnRH agonists have effectively reduced the fibroid size, but their use was accompanied by a rapid regrowth following discontinuation. Therefore, the literature states that goserelin therapy does not prevent or replace the eventual need for surgery. If used as a pre-operative adjunct, the literature recommends short-term treatment (six months or less).
Goserelin has been shown to be effective for the short-term (less than 6 months) preoperative adjunct to endometrial ablation or surgery for leiomyomata uteri (uterine fibroids).
Goserelin is under investigation as a method of prevention of chemotherapy-induced gonadal damage. In a prospective pilot study (n = 5), Franke, et al. (2005) explore the effects of goserelin acetate in women with Hodgkin's disease (HD) receiving chemotherapy while taking a continuous combined estrogen-progestin preparation as add-back on the prevention of premature ovarian failure (POF). Pre-menopausal women with HD received goserelin and add-back until polychemotherapy was completed. Every 4 weeks during treatment and thereafter, a hormonal profile (follicle-stimulating hormone (FSH), LH, 17beta-estradiol, progesterone and inhibin B) was measured until resumption of menstruation or the development of a hyper-gonadotropic state (2 x FSH greater than 30 U/l). All patients reached pre-pubertal status during treatment. Following cessation of goserelin therapy, 1 patient developed a hyper-gonadotropic state and 4 patients resumed menstruation. One of those patients became pregnant and delivered a healthy son. These investigators concluded that the effectiveness of GnRH agonist plus add-back on the prevention of POF during polychemotherapy in women with HD needs further elucidation in randomized controlled trials.
Del Mastro, et al. (2006) noted that standard methods to prevent chemotherapy-induced early menopause in young, breast cancer patients are unavailable to date. Pre-clinical data has suggested that LHRH analogs given during treatment can decrease the gonado-toxicity induced by chemotherapy. In a phase II clinical trial, these investigators evaluated the activity of such a method in young, breast cancer patients undergoing adjuvant chemotherapy. Pre-menopausal patients received goserelin 3.6 mg every 4 weeks before and during chemotherapy. According to 2-stage optimal phase II Simon design, treatment was considered clinically interesting if it was able to prevent menopause in 19 out of 29 patients of the study population. The resumption of ovarian function was defined by a resumption of menstrual activity or by a FSH value less than or equal to 40 IU/l within 12 months after the last cycle of chemotherapy. A total of 30 patients were enrolled and 29 were evaluable. Median age was 38 years (range 29 to 47 years). All but one patient received CEF regimen (cyclophosphamide, epirubicin, 5-fluorouracil). Resumption of menstrual activity was observed in 21 patients (72%; 95% CI 52 to 87%) and a FSH value less than or equal to 40 IU/l in 24 patients (83%; 95% CI 63 to 93%). Menses resumption was observed in 16 out of 17 patients (94%) with age less than 40 years and in 5 out of 12 patients (42 %) with age 40 years or over. These researchers concluded that goserelin given before and during chemotherapy may prevent premature menopause in the majority of patients. However, the different success rate by age indicates the need of a prospective evidence of the effectiveness of such a strategy.
Plenaxis:
Plenaxis (abarelix) is a gonadotropin-releasing hormone antagonist approved by the FDA in November 2003. It is indicated for the treatment of the symptoms of men with advanced prostate cancer who cannot take other hormone therapies and who have refused surgical castration. Plenaxis is marketed under a voluntary risk management program agreed to and administered by the sponsor that will restrict the use of Plenaxis to patients with advanced prostate cancer, who have no alternative therapy, because of an increased risk of serious, and potentially life-threatening, allergic reactions associated with its use.
In a phase III clinical study (n = 269), McLeod et al (2001) evaluated the levels of testosterone and other hormones in men with prostate cancer treated with abarelix versus leuprolide acetate. The authors concluded that treatment with abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, LH, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.
In another phase III clinical trial (n = 255), Trachtenberg et al (2002) reported that abarelix as monotherapy achieved medical castration significantly more rapidly than combination therapy (LHRH agonist and a non-steroidal anti-androgen) and avoided the testosterone surge characteristic of agonist therapy. Both treatments were equally effective in reducing serum prostate specific antigen, and achieving and maintaining castrate levels of testosterone.
Koch, et al. (2003) stated that abarelix provided a safe and effective medical alternative to surgical castration in symptomatic patients (n = 81) with advanced prostate cancer without the risk of the clinical flare associated with LHRH agonists.
Appendix
Medically Necessary Indications for Lupron
Limitations
Endometriosis
Up to six months - because of lack of safety data with long-term use, and concerns in available peer-reviewed medical literature regarding effects on bone density.
Lupron dosages greater than 3.75 mg per month or 11.25 mg per 3 months are subject to medical necessity review.
To decrease fibroid size prior to surgery
Up to three months - under accepted guidelines, does not prevent or replace the eventual need for surgery except in peri-menopausal women.
Lupron dosages greater than 3.75 mg per month or 11.25 mg per 3 months are subject to medical necessity review.
To decrease endometrial thickness prior to endometrial ablation
Up to two months.
Lupron dosages greater than 3.75 mg per month or 11.25 mg per 3 months are subject to medical necessity review.
For palliative treatment in members with advanced prostate cancer, defined as Stage III or Stage IV, that has metastasized or recurred after treatment, or patient refuses orchiectomy
1 mg given subcutaneously daily. If receiving leuprolide acetate suspension (Lupron Depot), dosing is 7.5 mg IM once monthly.
For true (central) precocious puberty, defined as sexual maturation before age 8 in girls and age 10 in boys, and tumor has been ruled out by lab tests, CT, MRI, or ultrasound
Lupron Depot Ped: 0.3 mg/kg every four weeks (minimum 7.5 mg).
Lupron injection: 50 mcg/kg daily. It may be medically necessary to titrate dosages upwards in order to achieve hormonal down-regulation.
Infertility (used in conjunction with urofollitropin or menotropins) to suppress luteinizing hormone (LH) production in members with documented premature LH surge, or used in “super-ovulation” regimens associated with in vitro fertilization
Note: Treatment of infertility may be subject to specific limitations under some benefit plans. Most HMO plans exclude injectable infertility drugs from coverage.
For treatment of metastatic breast cancer
Indicated where member is pre-menopausal and the disease has progressed or recurred after a trial of at least 3 months of tamoxifen
To suppress onset of puberty in adolescents with early onset of puberty on growth hormone therapy
Adolescent must meet medical necessity criteria for growth hormone supplementation, have early onset of puberty, and be below target growth range (within 1 standard deviation of mean height for age and sex)
For the treatment of women with chronic refractory pelvic pain
Indicated where attempts at medical therapy with analgesics and oral contraceptive have been unsuccessful.
CPT Codes / HCPCS Codes / ICD-9 Codes
Lupron (suspension and implant):
HCPCS codes covered if selection criteria are met:
J1950
Injection leuprolide acetate (for depot suspension), per 3.75 mg
J9217
Leuprolide acetate (for depot suspension), 7.5 mg
J9219
Leuprolide acetate implant, 65 mg
ICD-9 codes covered if selection criteria are met:
174.0 - 175.9
Malignant neoplasm of breast
185
Malignant neoplasm of prostate
218.0 - 218.9
Uterine leiomyoma
233.0
Carcinoma in situ of breast
233.4
Carcinoma in situ of prostate
259.1
Precocious sexual development and puberty, not elsewhere classified
617.0 - 617.9
Endometriosis
Lupron prior to endometrial ablation (see CPB 91):
ICD-9 codes covered if selection criteria are met:
626.2
Excessive or frequent menstruation
626.3
Puberty bleeding
627.0
Premenopausal menorrhagia
627.1
Postmenopausal bleeding
2 week Lupron kit:
HCPCS codes covered if selection criteria are met:
J9218
Leuprolide acetate, per 1 mg
Other HCPCS codes related to the CPB:
J3355
Injection, urofollitropin, 75 IU
S0122
Injection, menotropins, 75 IU
S0187
Tamoxifen citrate, oral, 10 mg
ICD-9 codes covered if selection criteria are met:
185
Malignant neoplasm of prostate
233.4
Carcinoma in situ of prostate
259.1
Precocious sexual development and puberty, not elsewhere classified
628.0 - 628.9
Infertility, female
ICD-9 codes not covered for indications listed in the CPB:
140.0 - 239.9
Neoplasms [when used for preservation of ovarian or testicular function during chemotherapy]
182.0
Malignant neoplasm of corpus uteri, except isthmus
183.0
Malignant neoplasm of ovary
198.6
Secondary malignant neoplasm of ovary
218.0 - 218.9
Uterine leiomyoma
256.4
Polycystic ovaries
625.4
Premenstrual tension syndromes
V58.11 - V58.12
Encounter for antineoplastic chemotherapy and immunotherapy [when used for preservation of ovarian or testicular function during chemotherapy]
Zoladex (Goserelin):
HCPCS codes covered if selection criteria are met:
J9202
Goserelin acetate implant, per 3.6 mg
ICD-9 codes covered if selection criteria are met:
174.0 - 175.9
Malignant neoplasm of breast
185
Malignant neoplasm of prostate
218.0 - 218.9
Uterine leiomyoma
233.0
Carcinoma in situ of breast
233.4
Carcinoma in situ of prostate
617.0 - 617.9
Endometriosis
625.3
Dysmenorrhea
628.0 - 628.9
Infertility, female
Zoladex prior to endometrial ablation (see CPB 91):
ICD-9 codes covered if selection criteria are met:
626.2
Excessive or frequent menstruation
626.3
Puberty bleeding
627.0
Premenopausal menorrhagia
627.1
Postmenopausal bleeding
ICD-9 codes not covered for indications listed in the CPB:
140.0 - 239.9
Neoplasms [when used for preservation of ovarian or testicular function during chemotherapy]
V58.11 - V58.12
Encounter for antineoplastic chemotherapy and immunotherapy [when used for preservation of ovarian or testicular function during chemotherapy]
Plenaxis (abarelix):
Other CPT codes related to the CPB:
54520 - 54535, 54690
HCPCS codes covered if selection criteria are met:
C9216
Injection, Abarelix for injectable suspension, per 10 mg (deleted 12-31-04)
J0128
Injection, abarelix, 10 mg
ICD-9 codes covered if selection criteria are met:
185
Malignant neoplasm of prostate
Other ICD-9 codes related to the CPB for Lupron, Zoladex, and Plenaxis:
253.3
Pituitary dwarfism
625.8 - 625.9
Other and unspecified symptoms associated with female genital organs
V58.11 - V58.12
Encounter for antineoplastic chemotherapy and immunotherapy
V66.0
Convalescence and palliative care following surgery
V66.1
Convalescence and palliative care following radiotherapy
V66.2
Convalescence and palliative care following chemotherapy
V66.7
Encounter for palliative care The above policy is based on the following references:
Lupron:
Olin BR, ed. Drug Facts and Comparisons. St. Louis, MO: JB Lippincott Company; 1992.
Conn MP, Crowley WF. Gonadotropin-releasing hormone and its analogues. N Engl J Med. 1991;324(2):93-103.
Higham JM. The medical management of menorrhagia. Br J Hosp Med. 1991;45:19-21.
Schriock ED. Practical aspects of pulsatile gonadotropin-releasing hormone administration. Am J Obstet Gynecol. 1990;163(5):1765-1770.
Gompel A, Mauvais-Jarvis P. Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea. Hum Reprod. 1988;3(4):473-477.
Macdonald R. Modern treatment of menorrhagia. Br J Obstet Gynecol. 1990;97:3-7.
Dodson WC, Hughes CL, Whitesides DB, et al. The effect of leuprolide acetate on ovulation induction with human menopausal gonadotropins in polycystic ovary syndrome. J Endocrin Metab. 1987;65(1):95-100.
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Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2001;(2):CD000547.
Breast cancer
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Endometriosis
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Premenstrual syndrome
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Zoladex
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baseline scan and bloodtest
Tues 17 July 2007
went for baseline scan and bloodtest today. results out about 4pm. was told to conitnue with lucrin for another 7 days before going back for another scan and bloodtest. was also told that the endometrium is thick at 8mm.
normally by this time of the cycle, (day 5 of the cycle after AF), the endometrium shd be about 2mm only. yet mine is 8mm, not sure how this will affect the IVF cycle.
I am so diasppointed by the extension of the lucrin jabs and to top that now the point about the thickened endometrium..i wonder all thse additional hurdles is some omen that i should consider ending the cycle.
the side effects of lucrin/lupron is really beyond my control..it made me tempermental, frustrated at the slightest thing and short tempered, not to mentioned fatigue and nausea. I am not sure if it's the stress adding or the meds, but it seems to have triggered off a fibromyglia flare as well, my ribs, hips and knee hurts like hell.
went for baseline scan and bloodtest today. results out about 4pm. was told to conitnue with lucrin for another 7 days before going back for another scan and bloodtest. was also told that the endometrium is thick at 8mm.
normally by this time of the cycle, (day 5 of the cycle after AF), the endometrium shd be about 2mm only. yet mine is 8mm, not sure how this will affect the IVF cycle.
I am so diasppointed by the extension of the lucrin jabs and to top that now the point about the thickened endometrium..i wonder all thse additional hurdles is some omen that i should consider ending the cycle.
the side effects of lucrin/lupron is really beyond my control..it made me tempermental, frustrated at the slightest thing and short tempered, not to mentioned fatigue and nausea. I am not sure if it's the stress adding or the meds, but it seems to have triggered off a fibromyglia flare as well, my ribs, hips and knee hurts like hell.
Friday, July 13, 2007
lucrin side effects
the days are getting harder to cope - perhaps it's the side effect of lucrin/lupron. been feeling moody, teary, and super tired. and guess what AF come by today which is only Day 25 of the cycle.
so far been on 11 days of lucrin jabs with baseline scanning next Tuesday. Hoping to be able to start puregon ASAP. i can't wait for it to end.
so far been on 11 days of lucrin jabs with baseline scanning next Tuesday. Hoping to be able to start puregon ASAP. i can't wait for it to end.
Tuesday, July 03, 2007
IVF Start of Lucrin cycle
Finally 3rd July 2007 came around, today is Day 16 of the IVF cycle and officially i got started on Lucrin. I was pretty worried about the jabs, who wouldn;t be? it turn out to be less painful and less complicated.
will start to jab myself tomorrow.
will start to jab myself tomorrow.
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