Treatment of menopausal symptoms with three low-dose continuous sequential 17β-estradiol/progesterone parenteral monthly formulations using novel non-polymeric microsphere technology

Figures & data

Figure 1. CONSORT Diagram displaying the process of participant recruitment of the study.

Table 1. Demographic and baseline characteristics of participants.

	Treatments
Characteristic	Group A n = 38	Group B n = 29	Group C n = 36	p Value
Age, median (interval)	49 (38–62)	49 (40–60)	47 (41–56)	0.088
Literacy (%)
Primary school	42.1	51.7	44.5	0.954
High school	34.2	34.4	33.3
College	23.7	13.8	22.2
Occupation (%)
Employment in the formal market	36.8	41.4	50.0	0.803
Working informally	10.5	10.3	11.1
Housewives	52.6	48.3	38.9
Reproductive history
Pregnancies, median (interval)	4 (1–7)	4 (1–12)	3 (1–6)	0.322
Vaginal deliveries, median (interval)	3 (1–6)	3 (1–9)	2 (1–6)	0.247
Cesarean sections, median (interval)	1.5 (1–3)	2 (1–3)	2 (1–3)	0.850
Practice sex regularly (%)	78.9	62.1	77.8	0.237
Menopause stage (%)
Perimenopausal women	57.9	51.7	58.3	0.841
Postmenopausal women	42.1	48.3	41.7

A: 0.5 mg E + 15 mg P; B: 1.0 mg E + 20 mg P; C: 1.0 mg E + 30 mg P.

Figure 2. Changes of mean daily number of hot flushes.

Table 2. Assessment of the severity of hot flashes, symptoms of urogenital atrophy and endometrial thickness per treatment group at proposed timelines.

	Treatments
	Group A				Group B				Group C
Symptoms	Baseline n = 38	Interim n = 37	Final n = 34	*p value	Baseline n = 29	Interim n = 25	Final n = 24	p Value	Baseline n = 36	Interim n = 29	Final n = 26	p Value
Severity of hot flashes
Moderate  Total number per month	150.6 ± 108.8	43.6 ± 25.9	25.9 ± 41.2	0.000	153.6 ± 203	23.0 ±  24.3	17.7 ± 39.9	0.000	157.5 ± 189.5	38.9 ± 43.3	16.1 ± 24.1	0.000
Severe
Total number per month	23.3 ± 50.3	4.7 ± 12.2	1.2 ±  4.1	0.001	31.4 ± 62.8	0.7 ± 3.6	0.9 ± 3.7	0.000	57.3 ± 107.1	2.4 ±  8.7	0.1 ± 0.4	0.000
Urogenital atrophy symptoms
Vaginal dryness (%)	50.0	24.3	17.6	0.001	58.6	12.0	8.3	0.000	36.1	31.0	23.1	0.407
Vaginal atrophy (%)	42.1	24.3	14.7	0.035	37.9	16.0	4.2	0.006	30.6	13.8	15.4	0.007
Dysuria (%)	28.9	2.7	2.9	0.002	10.3	4.0	0.0	0.097	19.4	10.3	0.0	0.042
Dyspareunia (%)	18.4	5.4	2.9	0.074	17.2	4.0	0.0	0.015	8.3	0.0	3.8	0.368
Post-coital vaginal bleeding (%)	2.6	2.7	0.0	0.368	6.9	0.0	0.0	0.135	5.6	0.0	0.0	0.368

	Group A				Group B				Group C
Endometrial thickness (mm)	Baseline		Final	p value	Baseline		Final	p value	Baseline		Final	p value
Perimenopausal women	6.72 ± 3.74 (n = 22)		5.25 ± 3.99 (n = 19)	0.261	6.64 ± 4.51 (n = 15)		6.83 ± 6.17 (n = 14)	0.93	5.98 ± 3.09 ( n = 21)		6.06 ± 3.97 (n = 15)	0.94
Postmenopausal women	4.02 ± 2.09 (n = 16)		5.22 ± 5.95 (n = 15)	0.518	3.92 ± 1.62 (n = 14)		3.90 ± 2.87 (n = 10)	0.988	4.18 ± 1.32 (n = 15)		3.16 ± 1.31 (n = 11)	0.053

A: 0.5 mg E + 15 mg P; B: 1.0 mg E + 20 mg P; C: 1.0 mg E + 30 mg P. Data are presented as mean ± standard deviations (SD) or percentages (%); evaluation stages: Baseline (at enrollment), interim (third month of follow-up), final (sixth month of follow-up).

*p value obtained when comparing final with baseline; endometrial thickness was assessed at baseline and at the sixth month.

Table 3. Frequency of adverse events per type of treatment.

		Treatment A n = 38	Treatment B n = 29	Treatment C n = 36
Signs and symptoms		%	%	%
General symptoms	Headache	–	–	–
Cardiovascular	Palpitation	–	–	–
	Tachycardia	–	–	–
	Digestive	Nausea	–	–	–
Musculoskeletal	Arthralgia	–	–	–
	Myalgias	2.6	–	2.8
	Nervous	Depression	–	–	–
Dizziness		–	–	–
Nervousness		–	–	2.8
Local symptoms		Pain	18.4	24.1	16.6
	Induration	–	–	2.8
		Edema	–	–	–
Special senses	Blurred vision	–	–	–
Urogenital	Increase of endometrial thickness	2.6	–	–
	Pelvic inflammation	–	–	–
	Mastalgia	2.6	–	–

A: 0.5 mg E + 15 mg P; B: 1.0 mg E + 20 mg P; C: 1.0 mg E + 30 mg P.

Figure 3. Percentage of amenorrhea during the follow-up among perimenopausal (A) and postmenopausal women (B).