norethindrone acetate and Uterine Neoplasms studies

norethisterone acetate : A 3-oxo Delta(4)-steroid that is norethisterone in which the hydroxy group has been converted to its acetate ester.

Research Excerpts

Excerpt	Relevance	Reference
"To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas."	9.27	Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial. ( Al-Hendy, A; Archer, DF; Bradley, L; Carr, BR; Chwalisz, K; Diamond, MP; Duan, WR; Dufek, MB; Gao, J; Owens, CD; Simon, JA; Soliman, AM; Stewart, EA; Watts, NB, 2018)
"Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women."	9.22	Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis. ( Ahmad, I; Muhammad, J; Norhayati, MN; Yusof, Y, 2022)
"To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids."	9.19	Long-term treatment of uterine fibroids with ulipristal acetate ☆. ( Barlow, DH; Bestel, E; Bouchard, P; Donnez, J; Donnez, O; Fauser, BC; Loumaye, E; Nouri, K; Osterloh, I; Palacios, S; Tomaszewski, J; Vázquez, F, 2014)
"This drug evaluation features the clinical results from previous and ongoing studies of relugolix, in combination with the add back therapy of estradiol (E2) and norethindrone acetate (NETA), as a novel, orally administered, nonpeptide antagonist of gonadotropin-releasing hormone (GnRH) for the management of heavy menstrual bleeding (HMB) in premenopausal women with UFs."	8.12	An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. ( Al-Hendy, A; Ali, M; Badary, OA; Chen, HY; Chiang, YF; Hsia, SM, 2022)
"To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas."	5.27	Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial. ( Al-Hendy, A; Archer, DF; Bradley, L; Carr, BR; Chwalisz, K; Diamond, MP; Duan, WR; Dufek, MB; Gao, J; Owens, CD; Simon, JA; Soliman, AM; Stewart, EA; Watts, NB, 2018)
"Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women."	5.22	Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis. ( Ahmad, I; Muhammad, J; Norhayati, MN; Yusof, Y, 2022)
"To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids."	5.19	Long-term treatment of uterine fibroids with ulipristal acetate ☆. ( Barlow, DH; Bestel, E; Bouchard, P; Donnez, J; Donnez, O; Fauser, BC; Loumaye, E; Nouri, K; Osterloh, I; Palacios, S; Tomaszewski, J; Vázquez, F, 2014)
"This drug evaluation features the clinical results from previous and ongoing studies of relugolix, in combination with the add back therapy of estradiol (E2) and norethindrone acetate (NETA), as a novel, orally administered, nonpeptide antagonist of gonadotropin-releasing hormone (GnRH) for the management of heavy menstrual bleeding (HMB) in premenopausal women with UFs."	4.12	An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. ( Al-Hendy, A; Ali, M; Badary, OA; Chen, HY; Chiang, YF; Hsia, SM, 2022)
"Postmenopausal osteoporosis affects 25 to 50% of older women and increases the risk for vertebral, hip, and other fractures."	3.76	The menopause. ( Gambrell, RD, 1986)
"The effect of steroids contained in oral contraceptives, namely ethinylestradiol:17 alpha-ethinyl-1,3,5,(10)-estratriene-3, 17-diol (E) and norethindrone acetate:17 beta-acetoxy-17-ethinyl-4-estren-3-one (N), on cell replication and human chorionic gonadotropin (hCG) secretion by choriocarcinoma cells in monolayer culture and by hydatidiform mole tissue maintained in organ culture were studied."	3.66	Failure of contraceptive steroids to modify human chorionic gonadotrophin secretion by hydatidiform mole tissue and choriocarcinoma cells in culture. ( Buchsbaum, HJ; Gal, D; MacDonald, PC; Porter, JC; Simpson, ER, 1981)
"Uterine fibroids are common non-cancerous neoplasm that cause heavy menstrual bleeding and other signs."	3.11	Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials. ( Al-Hendy, A; Archer, D; Bestel, E; Bradley, L; Donnez, J; Garner, E; Gotteland, JP; Humberstone, A; Loumaye, E; Marsh, E; Petraglia, F; Stewart, EA; Taylor, HS; Terrill, P; Watts, N, 2022)
"Uterine fibroids are a common cause of heavy menstrual bleeding and pain."	3.01	Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. ( Al-Hendy, A; Arjona Ferreira, JC; Critchley, HOD; Langenberg, AGM; Li, Y; Lukes, AS; McKain, L; Poindexter, AN; Stewart, EA; Venturella, R; Villarroel, C; Wagman, RB, 2021)
"The quality of the myometrial scar, defined by ultrasound evaluation, was similar in the two study groups both at one-week (p=0."	2.79	Preoperative treatment with letrozole in patients undergoing laparoscopic myomectomy of large uterine myomas: a prospective non-randomized study. ( Ferrero, S; Leone Roberti Maggiore, U; Scala, C; Venturini, PL, 2014)
"Uterine fibroids can cause heavy menstrual bleeding."	2.66	Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy). ( Lumbiganon, P; Pattanittum, P; Sangkomkamhang, US, 2020)
"The incidence of breast cancer was also significantly lower in the estrogen-progestogen users (66."	1.27	Use of progestogen therapy. ( Gambrell, RD, 1987)

Research

Studies (28)

Authors

Clinical Trials (7)

Trial Overview

Trial Outcomes

Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29

Timeframe	Studies, this research(%)	All Research%
pre-1990	14 (50.00)	18.7374
1990's	3 (10.71)	18.2507
2000's	1 (3.57)	29.6817
2010's	3 (10.71)	24.3611
2020's	7 (25.00)	2.80

Authors	Studies
Muhammad, J	1
Yusof, Y	1
Ahmad, I	1
Norhayati, MN	1
Ali, M	1
Chen, HY	1
Chiang, YF	1
Badary, OA	1
Hsia, SM	1
Al-Hendy, A	4
Donnez, J	3
Taylor, HS	1
Stewart, EA	3
Bradley, L	2
Marsh, E	1
Archer, D	1
Petraglia, F	1
Watts, N	1
Gotteland, JP	1
Bestel, E	2
Terrill, P	1
Loumaye, E	2
Humberstone, A	1
Garner, E	1
Syed, YY	1
Sangkomkamhang, US	1
Lumbiganon, P	1
Pattanittum, P	1
Lukes, AS	1
Poindexter, AN	1
Venturella, R	1
Villarroel, C	1
Critchley, HOD	1
Li, Y	1
McKain, L	1
Arjona Ferreira, JC	1
Langenberg, AGM	1
Wagman, RB	1
Carr, BR	1
Archer, DF	1
Watts, NB	1
Diamond, MP	1
Gao, J	1
Owens, CD	1
Chwalisz, K	1
Duan, WR	1
Soliman, AM	1
Dufek, MB	1
Simon, JA	1
Vázquez, F	1
Tomaszewski, J	1
Nouri, K	1
Bouchard, P	1
Fauser, BC	1
Barlow, DH	1
Palacios, S	1
Donnez, O	1
Osterloh, I	1
Leone Roberti Maggiore, U	1
Scala, C	1
Venturini, PL	1
Ferrero, S	1
Simsek, T	1
Karakus, C	1
Trak, B	1
BRISCOE, CC	1
Fraser, IS	1
Guillebaud, J	1
Gambrell, RD	3
Massey, FM	1
Castaneda, TA	1
Ugenas, AJ	1
Ricci, CA	1
Wright, JM	1
Quinn, MA	1
Schindler, C	2
Rodriguez, L	1
Gal, D	1
Simpson, ER	1
Porter, JC	1
MacDonald, PC	1
Buchsbaum, HJ	1
Schober, J	1
Ursic-Vrscaj, M	1
Lai, FM	1
Wong, FW	1
Allen, PW	1
Krafft, W	2
Steuckardt, R	1
König, EM	1
Schirmer, A	1
Schmeisser, G	1
Brückmann, D	1
Griesinger, R	1
Schindler, AE	1
Whitehead, MI	1
Fraser, D	1
Casanas-Roux, F	1
Caprasse, J	1
Ferin, J	1
Thomas, K	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 3, Multicentre, Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy and Safety of Daily Oral Administration of OBE2109 Alone and in Combination With Add-back Therapy for the Management of Heavy Menstrual Bleeding Associat[NCT03070951]	Phase 3	511 participants (Actual)	Interventional	2017-05-23	Completed
A Phase 3, Multicentre, Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy and Safety of Daily Oral Administration of OBE2109 Alone and in Combination With Add-back Therapy for the Management of Heavy Menstrual Bleeding Associat[NCT03070899]	Phase 3	526 participants (Actual)	Interventional	2017-04-20	Completed
LIBERTY 2: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Co-Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associate[NCT03103087]	Phase 3	382 participants (Actual)	Interventional	2017-06-14	Completed
LIBERTY 1: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Co-Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associate[NCT03049735]	Phase 3	388 participants (Actual)	Interventional	2017-04-26	Completed
A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids[NCT01817530]	Phase 2	571 participants (Actual)	Interventional	2013-04-08	Completed
A Phase III, Multicentre, Clinical Study Investigating the Efficacy and Safety of 3-months Open-label Treatment With PGL4001, Followed by a Randomised, Double-blind Placebo Controlled Period of 10 Days Treatment With Progestin, in Subjects With Myomas and[NCT01156857]	Phase 3	209 participants (Actual)	Interventional	2010-07-31	Completed
A Phase III, Multicentre, Clinical Study Investigating the Efficacy and Safety of Three Successive Periods of 3-month Open-label PGL4001 Treatment, Each Followed by Ten Days of Double-blind Treatment With Progestin or Placebo and a Drug-free Period Until [NCT01252069]	Phase 3	132 participants (Actual)	Interventional	2011-01-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.4
Placebo (Group C)	-0.7

"PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.7
Placebo (Group C)	-0.8

"Blood samples for determination of E2 serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire

Intervention	pg/mL (Mean)
Relugolix Plus E2/NETA (Group A)	-22.30

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-2.0
Placebo (Group C)	-0.8

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-2.0
Placebo (Group C)	-0.7

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.8
Placebo (Group C)	-0.6

"The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.8
Placebo (Group C)	-0.9

Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.8
Placebo (Group C)	-1.0

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	43.6
Placebo (Group C)	17.1

"Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good). LS means and p-value for test of difference was relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score

Intervention	units on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	44.4
Placebo (Group C)	16.5

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of time, most of the time and all of the time.) Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-36.1
Placebo (Group C)	-13.7

"The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question [Q] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5), raw scores were transformed to a normalized score: Transformed Score = [(Actual raw score - lowest possible raw score)/(Possible raw score range)]*100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates symptom severity.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms" (NCT03103087)
Timeframe: Baseline Week 24

Change From Baseline In E2 Serum Concentration At Week 24

Intervention	units on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-51.7
Placebo (Group C)	-18.3

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline In Follicle Stimulating Serum Concentration At Week 24

Intervention	pg/mL (Mean)
Relugolix Plus E2/NETA (Group A)	-22.30
Placebo (Group C)	39.85

Change From Baseline In Luteinizing Serum Concentration At Week 24

Intervention	IU/L (Mean)
Relugolix Plus E2/NETA (Group A)	-5.47
Placebo (Group C)	-0.67

Change From Baseline In Progesterone Serum Concentration At Week 24

Intervention	IU/L (Mean)
Relugolix Plus E2/NETA (Group A)	-3.10
Placebo (Group C)	3.04

Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score

Intervention	ng/mL (Mean)
Relugolix Plus E2/NETA (Group A)	0.12
Placebo (Group C)	3.48

"The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most participants (heavy bleeding during the menstrual period [Question 1], passing blood clots during the menstrual period [Question 2], and feeling tightness or pressure in the pelvic area [Question 5]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-51.7
Placebo (Group C)	-18.3

"The UFS-QoL total score was the sum of 6 subscales (concern, activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization

Intervention	units on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	37.8
Placebo (Group C)	13.8

"Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to the last 35 days of treatment (up to 24 weeks)

Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	34
Placebo (Group C)	17

Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	48
Placebo (Group C)	34

Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	19
Placebo (Group C)	2

Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	35
Placebo (Group C)	18

"Responder was defined as meeting a meaningful change threshold, set as a 20-point change from Baseline, in the Bleeding And Pelvic Discomfort Scale at Week 24 on the transformed score.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	79
Placebo (Group C)	37

Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	78
Placebo (Group C)	42

"Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 12

Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline

Intervention	percent change (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-0.819
Relugolix Plus Delayed E2/NETA (Group B)	-1.919

Percent Change From Baseline At Week 24 In MBL Volume

Intervention	percent change (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	24.3
Placebo (Group C)	4.3

"MBL volume was measured using the alkaline hematin method. Least square (LS) means for test of difference is Relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume

Intervention	percent change (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-84.3
Placebo (Group C)	-15.1

"The volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline Week 24

Percent Change From Baseline At Week 24 In Uterine Volume

Intervention	percent change (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-17.4
Placebo (Group C)	-7.4

"The volume of the uterus was measured by transvaginal or transabdominal ultrasound.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 24

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12

Intervention	percent change (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-13.8
Placebo (Group C)	-1.5

An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term. Reported confidence interval (CI) based on exact binomial 95% CI (Clopper-Pearson). As per the objective of the study, the secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below. (NCT03103087)
Timeframe: Baseline through Week 12

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24

Intervention	percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	5.56
Relugolix Plus Delayed E2/NETA (Group B)	35.71

"An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.~Reported percentages based on the total number of participants in each treatment group.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline through Week 24

Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA

Intervention	percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	6.3
Placebo (Group C)	3.9

"A responder was a participant who had MBL volume of < 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.~As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to the last 35 days of treatment (up to Week 24)

Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24

Intervention	Percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	71.2
Placebo (Group C)	14.73

"Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤ 10.5 gram (g)/deciliter (dL) at Baseline and reported at Week 24.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA with placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment

Intervention	Percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	61.29
Placebo (Group C)	5.41

"Uterine fibroid-associated pain was assessed by a pain numerical rating scale (NRS). The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~Participants were asked to document, in an e-Diary, the worst pain associated with their uterine fibroids that they experienced during the last 24 hours, every day until the end of study drug administration. Pain evaluable participants, defined as those who had maximum NRS score ≥ 4 at baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary, were analyzed.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

Intervention	percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	47.06
Placebo (Group C)	17.07

"Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits:~No feminine product returned due to reported amenorrhea;~No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (e-Diary) data indicating infrequent non-cyclic bleeding/spotting;~Feminine product collection with a negligible observed MBL volume coupled with e-Diary data indicating infrequent non-cyclic bleeding/spotting.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)

Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24

Intervention	Percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	50.40
Placebo (Group C)	3.10

"Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03103087)
Timeframe: Week 24

Sustained Amenorrhea Rate (No Or Negligible Bleeding)

Intervention	pg/mL (Mean)
Relugolix Plus E2/NETA (Group A)	45.34

"Sustained amenorrhea is defined as participants time to achieve and maintain amenorrhea until the date of last study drug.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Week 24

Time To Achieving Amenorrhea (No Or Negligible Bleeding)

Intervention	Participants (Count of Participants)
Relugolix Plus E2/NETA (Group A)	63
Placebo (Group C)	4

"Time to amenorrhea was defined as the weeks from date of first dose of study drug to the start of amenorrhea.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)

Intervention	weeks (Median)
Relugolix Plus E2/NETA (Group A)	8.9
Placebo (Group C)	NA

"Sustained amenorrhea status as determined based on time to achieve and maintain amenorrhea status.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Time To MBL Response

Intervention	weeks (Median)
Relugolix Plus E2/NETA (Group A)	16.3
Placebo (Group C)	NA

"Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24

Intervention	weeks (Median)
Relugolix Plus E2/NETA (Group A)	8.4
Placebo (Group C)	27.1

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at Baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24

Intervention	Participants (Count of Participants)
	1 Category improvement (-1)	2 Category improvement (-2)	3 Category improvement (-3)	4 Category improvement (-4)
Placebo (Group C)	19	13	10	2
Relugolix Plus E2/NETA (Group A)	13	30	18	4

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA

Intervention	Participants (Count of Participants)
	1 Category improvement (-1)	3 Category improvement (-3)	2 Category improvement (-2)	4 Category improvement (-4)
Placebo (Group C)	21	8	18	2
Relugolix Plus E2/NETA (Group A)	7	22	29	10

"BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck (same leg across participants) at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. For Relugolix plus E2/NETA Lumbar Spine (L1 to L4), number (n)=95.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only rel" (NCT03103087)
Timeframe: Baseline through Week 24

Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24

Intervention	percent change (Least Squares Mean)
	Lumbar Spine (L1-L4)	Total Hip	Femoral Neck
Placebo (Group C)	0.315	-0.044	0.019
Relugolix Plus E2/NETA (Group A)	-0.126	-0.173	-0.684

Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29

Intervention	ng/mL (Mean)
	Relugolix	NET
Relugolix Plus E2/NETA (Group A)	1.96	0.28

Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.5
Placebo (Group C)	-0.4

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Predose Concentrations Of Estradiol In The Relugolix Plus E2/NETA Group

Intervention	score on a scale (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-1.6
Placebo (Group C)	-0.5

"Blood samples for determination of serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities

Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score

Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)

"The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question [Q] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5). raw scores were transformed to a normalized score: Transformed Score = [(Actual raw score - lowest possible raw score)/(Possible raw score range)] * 100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.~As per the study objective, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only these two arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In E2 Serum Concentration At Week 24

Change From Baseline In Follicle Stimulating Serum Concentration At Week 24

Change From Baseline In Luteinizing Serum Concentration At Week 24

Change From Baseline In Progesterone Serum Concentration At Week 24

Change From Baseline In UFS-QoL Bleeding And Pelvic Discomfort Scale Score

"The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most patients (heavy bleeding during the menstrual period [Question 1], passing blood clots during the menstrual period [Question 2], and feeling tightness or pressure in the pelvic area [Question 5]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In UFS-QoL Score By Health-Related Quality Of Life Total Score

"Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to the last 35 days of treatment (up to 24 weeks)

Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline

Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24

Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal

Number Of Responders With At Least 20 Points Decrease In UFS-QoL Bleeding And Pelvic Discomfort Scale Score

"A Responder was defined as meeting a meaningful change threshold, set as a 20-point change from Baseline, in the Bleeding And Pelvic Discomfort Scale at Week 24 on the transformed score.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score

Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 To L4), As Assessed By DXA

"Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD.~As per the objective of the study, the pre-specified secondary analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below." (NCT03049735)
Timeframe: Baseline, Week 12

Percent Change From Baseline At Week 24 In MBL Volume

MBL volume was measured using the alkaline hematin method. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Baseline, Week 24

Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume

Percent Change From Baseline At Week 24 In Uterine Volume

Percent Change From Baseline In Hemoglobin For Women With a Hemoglobin ≤ 10.5 g/dL At Baseline

"LS means and p-value for test of difference is relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Week 24

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12

"An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.~Reported CI based on exact binomial 95% CI (Clopper-Pearson).~As per the objective of the study, this secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below." (NCT03049735)
Timeframe: Baseline through Week 12

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24

Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA

"A responder was a participant who had MBL volume of < 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.~As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)

Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24

Percentage Of Participants With A Maximum NRS Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment

"Uterine fibroid-associated pain was assessed by a pain numerical rating scale (NRS). The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~Participants were asked to document, in an e-Diary, the worst pain associated with their uterine fibroids that they experienced during the last 24 hours, every day until the end of study drug administration. Pain evaluable participants, defined as those who had maximum NRS score ≥ 4 at Baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary, were analyzed.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

"Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits:~No feminine product returned due to reported amenorrhea;~No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (eDiary) data indicating infrequent non-cyclic bleeding/spotting;~Feminine product collection with a negligible observed MBL volume coupled with eDiary data indicating infrequent non-cyclic bleeding/spotting.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)

Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24

Sustained Amenorrhea Rate (No Or Negligible Bleeding)

Time To Achieving Amenorrhea (No Or Negligible Bleeding)

Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)

Time To MBL Response

"Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method. MBL volume was measured using the alkaline hematin method.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck

"BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Predose Trough Concentrations Of Relugolix And Norethindrone (NET) In The Relugolix Plus E2/NETA Group At Week 24

"Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics.~As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03049735)
Timeframe: Week 24

Change in Bleeding Severity Scores From Baseline at the Final Month

The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug. (NCT01817530)
Timeframe: Baseline, Final Month (last 28 days of treatment)

Mean Change in Hemoglobin Concentration From Baseline to Final Visit

Baseline is defined as the last measurement prior to the first dose of study drug. (NCT01817530)
Timeframe: Baseline, Final Visit during treatment period (Month 6 or early termination)

Mean Change in the Number of Bleeding Days From Baseline to Month 6

The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug. (NCT01817530)
Timeframe: Baseline, Month 6

Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6

The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug. (NCT01817530)
Timeframe: Baseline, Month 6

Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment

Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment. (NCT01817530)
Timeframe: Last 56 days of treatment (after 10 days from first dose date)

Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month

Percentage of participants who achieved an MBL volume of < 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Final Month (last 28 days of treatment)

Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment

Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment. (NCT01817530)
Timeframe: Last 56 days of treatment (after 10 days from first dose date)

Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month

Percentage of participants with a >= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, Final Month (last 28 days of treatment)

Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment

The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)

Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment

The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)

Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month

The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of < 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, Final Month (last 28 days of treatment)

Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire

The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug. (NCT01817530)
Timeframe: Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168

Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Intervention	pg/mL (Mean)
Relugolix Plus E2/NETA (Group A)	-22.95
Placebo (Group C)	51.72

Intervention	percent change (Least Squares Mean)
Relugolix Plus E2/NETA (Group A)	-0.470
Relugolix Plus Delayed E2/NETA (Group B)	-1.995

Intervention	percentage of participants (Number)
Relugolix Plus E2/NETA (Group A)	10.94
Relugolix Plus Delayed E2/NETA (Group B)	36.36

Intervention	percent change (Least Squares Mean)
	Lumbar Spine (L1 to L4)	Total Hip	Femoral Neck
Placebo (Group C)	0.052	0.549	0.307
Relugolix Plus E2/NETA (Group A)	-0.356	0.023	-0.262

Intervention	units on a scale (Least Squares Mean)
Cohort 1: Placebo	-0.3
Cohort 1: Elagolix 300 mg BID	-0.7
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	-0.4
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	-0.1
Cohort 2: Placebo	-0.2
Cohort 2: Elagolix 600 mg QD	-0.4
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	-0.3
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	-0.1

Intervention	days (Least Squares Mean)
Cohort 1: Placebo	-1.2
Cohort 1: Elagolix 300 mg BID	-4.9
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	-2.7
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	-1.1
Cohort 2: Placebo	-1.4
Cohort 2: Elagolix 600 mg QD	-3.3
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	-1.3
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	-1.8

Intervention	percentage of participants (Number)
Cohort 1: Placebo	1.6
Cohort 1: Elagolix 300 mg BID	56.1
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	33.3
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	28.3
Cohort 2: Placebo	1.3
Cohort 2: Elagolix 600 mg QD	50.7
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	17.5
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	22.7

Intervention	percentage of participants (Number)
Cohort 1: Placebo	32.81
Cohort 1: Elagolix 300 mg BID	91.94
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	88.52
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	79.03
Cohort 2: Placebo	36.84
Cohort 2: Elagolix 600 mg QD	91.55
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	72.6
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	85.53

Intervention	percentage of participants (Number)
Cohort 1: Placebo	1.6
Cohort 1: Elagolix 300 mg BID	75.4
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	52.6
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	43.3
Cohort 2: Placebo	2.7
Cohort 2: Elagolix 600 mg QD	67.2
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	31.7
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	34.8

Intervention	percentage of participants (Number)
Cohort 1: Placebo	31.25
Cohort 1: Elagolix 300 mg BID	93.55
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	86.89
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	82.26
Cohort 2: Placebo	35.53
Cohort 2: Elagolix 600 mg QD	90.14
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	79.45
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	85.53

Intervention	percentage of participants (Number)
Cohort 1: Placebo	11.29
Cohort 1: Elagolix 300 mg BID	94.83
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	88.14
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	85.00
Cohort 2: Placebo	18.42
Cohort 2: Elagolix 600 mg QD	85.29
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	67.19
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	77.14

Intervention	percentage of participants (Number)
Cohort 1: Placebo	19.67
Cohort 1: Elagolix 300 mg BID	96.43
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	89.47
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	79.31
Cohort 2: Placebo	21.62
Cohort 2: Elagolix 600 mg QD	86.36
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	74.19
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	72.31

Intervention	percentage of participants (Number)
Cohort 1: Placebo	26.56
Cohort 1: Elagolix 300 mg BID	91.94
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	85.25
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	79.03
Cohort 2: Placebo	31.58
Cohort 2: Elagolix 600 mg QD	90.14
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	72.6
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	81.58

Intervention	units on a scale (Least Squares Mean)
	Days 1-28	Days 29-56	Days 57-84	Days 85-112	Days 113-140	Days 141-168	Final Month	PT Days 1-28	PT Days 29-56	PT Days 57-84	PT Days 85-112	PT Days 113-140	PT Days 141-168
Cohort 1: Elagolix 300 mg BID	-3.4	-5.8	-7.2	-7.8	-7.6	-8.0	-6.7	-5.2	-4.1	-4.0	-6.4	-3.1	-8.0
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	-3.1	-4.4	-4.1	-5.2	-5.3	-5.1	-4.1	-3.8	-1.0	-2.1	-4.8	1.3	4.1
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	-1.4	-2.9	-3.2	-3.7	-3.4	-3.3	-3.5	-3.0	0.0	-1.1	0.7	1.4	-3.3
Cohort 1: Placebo	-3.3	-4.5	-5.6	-7.0	-4.1	-6.8	-5.3	-5.6	-5.7	-5.4	-4.4	3.4	7.5
Cohort 2: Elagolix 600 mg QD	-2.7	-4.2	-4.5	-5.1	-5.5	-5.9	-4.0	-3.8	-2.8	-2.0	-2.4	-17.3	-3.1
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	-2.1	-2.2	-2.2	-3.6	-4.0	-4.4	-3.3	-2.0	-2.7	-1.6	-3.0	-5.6	-3.3
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	0.0	-2.3	-3.8	-4.1	-5.3	-4.8	-2.3	-2.3	-2.5	-3.9	-5.0	-7.0	-6.4
Cohort 2: Placebo	0.4	-0.3	0.1	-0.2	0.1	-0.4	-0.8	-0.8	-0.2	-0.5	-2.7	-6.2	-10.5

Intervention	percentage change (Mean)
	Month 3	Month 6	Final Visit
Cohort 1: Elagolix 300 mg BID	-35.5	-36.1	-35.6
Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD	-20.3	-19.6	20.0
Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD	-3.7	0.0	-2.7
Cohort 1: Placebo	6.9	13.2	9.0
Cohort 2: Elagolix 600 mg QD	-33.6	-33.5	-34.8
Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD	-17.2	-12.2	-12.8
Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD	-1.9	-0.7	0.0
Cohort 2: Placebo	6.7	1.4	3.0

Article	Year
Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis. BMC women's health, 2022, 01-15, Volume: 22, Issue:1 Topics: Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Hydrocarbons, Fluorinated; Leiomyoma; Men	2022
Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids. Drugs, 2022, Volume: 82, Issue:15 Topics: Acetates; Estradiol; Female; Humans; Leiomyoma; Menorrhagia; Norethindrone; Norethindrone Acetate; U	2022
Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy). The Cochrane database of systematic reviews, 2020, 11-23, Volume: 11 Topics: Adult; Antineoplastic Agents, Hormonal; Bias; Contraceptives, Oral; Desogestrel; Female; Goserelin;	2020
Long acting injectable hormonal contraceptives. Clinical reproduction and fertility, 1982, Volume: 1, Issue:1 Topics: Animals; Breast Neoplasms; Contraceptive Agents; Delayed-Action Preparations; Dogs; Drug Administrat	1982
The effects of estrogens and progestogens on the endometrium. Modern approach to treatment. Obstetrics and gynecology clinics of North America, 1987, Volume: 14, Issue:1 Topics: Drug Administration Schedule; Endometrium; Estrogens; Female; Humans; Menopause; Middle Aged; Noreth	1987
The menopause. Investigative radiology, 1986, Volume: 21, Issue:4 Topics: Adult; Breast Neoplasms; Calcium; Clinical Trials as Topic; Coronary Disease; Estrogens; Female; Gal	1986

Article	Year
An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. Expert opinion on pharmacotherapy, 2022, Volume: 23, Issue:4 Topics: Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Menorrhagia; Norethindrone Ace	2022
Oriahnn for fibroid-associated heavy menstrual bleeding. The Medical letter on drugs and therapeutics, 2021, Apr-05, Volume: 63, Issue:1621 Topics: Drug Combinations; Estradiol; Female; Humans; Hydrocarbons, Fluorinated; Leiomyoma; Menorrhagia; Men	2021
ACUTE HEMORRHAGIC DEGENERATION OF A LEIOMYOMA FOLLOWING NORETHINDRONE ACETATE: REPORT OF A CASE. Obstetrics and gynecology, 1964, Volume: 23 Topics: Female; Humans; Leiomyoma; Neoplasms; Norethindrone; Norethindrone Acetate; Pathology; Surgical Proc	1964
Are there any absolute medical contraindications to the progestogen only oral contraceptive? British medical journal (Clinical research ed.), 1984, Oct-20, Volume: 289, Issue:6451 Topics: Contraceptives, Oral; Contraceptives, Oral, Hormonal; Female; Humans; Hydatidiform Mole; Norethindro	1984
Use of the progestogen challenge test to reduce the risk of endometrial cancer. Obstetrics and gynecology, 1980, Volume: 55, Issue:6 Topics: Adenocarcinoma; Aged; Endometrial Hyperplasia; Estrogens; Female; Humans; Medroxyprogesterone; Medro	1980
Is endocrine status relevant to treatment planning in patients with gynaecological cancer? The Australian & New Zealand journal of obstetrics & gynaecology, 1984, Volume: 24, Issue:2 Topics: Carcinoma; Female; Humans; Norethindrone; Norethindrone Acetate; Ovarian Neoplasms; Receptors, Estro	1984
[Comparative studies of the effect on the in vitro growth of endometrial cancers of hydroxyprogesterone caproate, norethisterone acetate and D-norgestrel]. Zentralblatt fur Gynakologie, 1984, Volume: 106, Issue:7 Topics: 17 alpha-Hydroxyprogesterone Caproate; Cells, Cultured; Drug Evaluation, Preclinical; Drug Resistanc	1984
Failure of contraceptive steroids to modify human chorionic gonadotrophin secretion by hydatidiform mole tissue and choriocarcinoma cells in culture. Steroids, 1981, Volume: 37, Issue:6 Topics: Cell Division; Cells, Cultured; Choriocarcinoma; Chorionic Gonadotropin; Contraceptives, Oral; Contr	1981
[Results obtained from gestagen treatment of patients for endometrial carcinoma, with particular reference to results obtained from in vitro tests before treatment (author's transl)]. Zentralblatt fur Gynakologie, 1981, Volume: 103, Issue:12 Topics: 17 alpha-Hydroxyprogesterone Caproate; Drug Resistance; Female; Humans; Hydroxyprogesterones; Neopla	1981
Hormone replacement therapy after uterine leiomyosarcoma treatment. Case reports. European journal of gynaecological oncology, 1999, Volume: 20, Issue:5-6 Topics: Adult; Climacteric; Disease Progression; Estradiol; Estrogen Replacement Therapy; Female; Humans; Le	1999
Diffuse uterine leiomyomatosis with hemorrhage. Archives of pathology & laboratory medicine, 1991, Volume: 115, Issue:8 Topics: Adult; Clomiphene; Female; Humans; Immunohistochemistry; Infertility, Female; Leiomyoma; Menorrhagia	1991
[Therapy of juvenile adenomatous hyperplasia of the endometrium by progesterone stimulation]. Zentralblatt fur Gynakologie, 1989, Volume: 111, Issue:12 Topics: Adenoma; Adolescent; Adult; Chlormadinone Acetate; Drug Administration Schedule; Endometrial Hyperpl	1989
[Therapy with gestagens in hyperplastic changes of the endometrium]. Geburtshilfe und Frauenheilkunde, 1986, Volume: 46, Issue:10 Topics: Adenocarcinoma; Adenoma; Endometrial Hyperplasia; Endometrium; Female; Humans; Medroxyprogesterone;	1986
Use of progestogen therapy. American journal of obstetrics and gynecology, 1987, Volume: 156, Issue:5 Topics: Breast Neoplasms; Cholesterol, HDL; Drug Therapy, Combination; Estrogens; Female; Humans; Menopause;	1987
Cyclic changes in ciliation, cell height, and mitotic activity in human tubal epithelium during reproductive life. Fertility and sterility, 1985, Volume: 43, Issue:4 Topics: Cell Cycle; Epithelial Cells; Estrogens; Fallopian Tubes; Female; Follicular Phase; Humans; Leiomyom	1985