Table 1.

Review of Studies Included in the Meta-Analysis

Author, location	Patient population	Study type	GnRHa, dose, timing	Chemotherapy	Definition of premature ovarian failure	Duration of patient follow-up
Blumenfeld et al. 20056 Israel	Lymphoma (Hodgkin and non-Hodgkin) Age 14–40	Prospective Controls: referred after therapy started or did not want GnRHa	Triptorelin 3.75 mg i.m. q4wks	Various XRT in 65%	Amenorrhea, estradiol <100 pmol/L, and FSH > 25 IU/L	Not reported
Blumenfeld et al. 200010 Israel	SLE (7) Nephrotic syndrome (1)	Prospective. Nonrandomized	Triptorelin 3.75 mg i.m. q4wks	CYCa or chlorambucil with CYC dose GnRHa: 6–11 g No GnRHa: 4–26.5 g	Amenorrhea, estradiol <100 pmol/L, and FSH > 25 IU/L	GnRHa: 2–15 years (average 8.3 years) No GnRHa: 4–15 years (average 9 years)
Castelo-Branco et al. 200711 Spain	Hodgkin's Age 14–45	Prospective, Nonrandomized.	Triptorelin 3.75 mg i.m. q4wks (1st dose 1–2 wks before chemotherapy) And Tibolone qd to decrease low estrogen effects	Various: ABVD: 10 of each group ABVD + XRT: 10 GnRH, 7 control	No regular Menses	Not reported, but all patients enrolled “during the same period” of time
Dann et al. 200512 Israel	Non-Hodgkin's lymphoma Age 18–40 (median 27)	Prospective. Offered GnRHa to women under 40. Nonrandomized	Triptorelin 3.75 mg i.m. q4wks	Cumulative CYC dose: 8,000–12,000 mg/m2  10: CYC 3,000 mg/m2 over 2 days + doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 1: CYC 2500 mg/m2 2: CYC 2000 mg/m2	Cyclic ovarian function = regular menses + normal gonadotropin and sex steroid levels or follicles on U/S or pregnancy	Follow-up: 70 months (23–99) GnRHa: 23–95 months No GnRHa: 23–99 months
Loverro, et al. 20077 Italy	Hodgkin's lymphoma Mean age 24.3 ± 6.6	Prospective randomized	Triptorelin 3.25 mg i.m. qmonth Or Triptorelin 11.25 mg i.m. q3months	13 patients: ABVD × 6 13 patients: ABVD × 5 alternating with C(M)OPP 3 patients: C(M)OPP alternative ABV, then DHAP 24 patients: Supradiaphragmatic radiation	No menses within 12 months	GnRHa: 2.4 ± 1.7 years No GnRHa: 5.9 ± 4.5 years
Pereyra Pacheco et al. 200113 Argentina	Adolescents with leukemia Group B: Postmenarche, treated with GnRHa Group C: Postmenarche, no GnRHa.	Nonrandomized, nonblinded. Prospective for GnRHa patients, retrospective for controls.	Leuprolide 3.75 mg IM q4wks Short-acting leuprolide given daily the 1st 2 weeks of treatment so chemotherapy could be started immediately	Group B1: BMT6 Group B2: CVPP7 or ABVD, no BMT Group C: BMT	Amenorrhea	Group B: 5 yrs. Group C: 6 yrs
Petri et al. 200414 Johns Hopkins	Severe SLE Age < 40	Prospective cohort	Leuprolide 3.75 mg i.m. q4wks	Monthly CYC × 6, then q3months for 18 months Or High-dose CYC (50 mg/kg × d)	FSH > 25	Not reported
Somers et al. 2005.15 University of Michigan	SLE Age 17–32 follow-up minimum  3 years	Prospective for GnRHa patients, retrospective for controls	Leuprolide 3.75 mg i.m. q4wks (10 days prior to next CYC dose) 1st dose usually given after 1st CYC dose Depot provera q3m and estrogen patch	CYC i.v. monthly × 6 months, then AZA or MMF Or CYC i.v. qm × 4	FSH > 40 and amenorrhea × 12 months Median time to POF: 4.3 years	Minimum 3 years GnRHa: 3–9 years (median 5 years) No GnRHa: 4–17 years (median 10 years)
Waxman et al. 19875 U.K.	Advanced Hodgkin's disease	Prospective, randomized	Buserelin 200 μg t.i.d. intranasal, starting 1 week before chemotherapy	Up to 6 cycles of MVPP	Amenorrhea	Mean: GnRHa: 2.3 years No GnRHa: 2.0 years

^aCYC, cyclophosphamide, ABVD; adriamycin, bleomycin, vinblastine, dacarbazine; C(M)OPP, cyclophosphamide, vincristine, procarbazine, prednisone; ABV, adriamycin, bleomycin, vinblastine; DHAP, dexamethasone, cytarabine, cisplatin; BMT, bone marrow transplant; CVPP, cyclophosphamide, vinblastine, procarbazine, prednisone; AZA, azathioprine; MMF, mycophenolate mofetil; MVPP, mustine, vinblastine, procarbazine, prednisolone; XRT, radiation; U/s, ultrasound.