Table 1. Open in new tab Effect of MHT...

Name	Design	Population	Age (y)	Treatment Length	MHT	Technique	Effect^a
Women Without Diabetes
PEPI (2)	RCT	788	45–64	3 y	CE 0.625 mg ± progestin	FG, fasting insulin	IR ↓
HERS (3)	RCT	2029	67 ± 7	4.1 y	CE 0.625 mg/MPA 2.5 mg	Incident diabetes FG	Diabetes ↓ 35%
WHI (4, 5, 87)	RCT	15,641	50–79	5.6 y	CE 0.625 mg/MPA 2.5 mg	Self-report	Diabetes ↓ 19%–21%
10,739	50–79	7.1 y	CE 0.625 mg	Self-report	Diabetes ↓ 12%–14%
KEEPS (77)	RCT	727	42–58	4 y	CE 0.45 mg/o-P4 200 mg	HOMA-IR	IR ↓
t-E2 50 µg/o-P4 200 mg	HOMA-IR	IR ↓ (ns)
Lobo (78)	RCT	745	40–65	1 y	CE 0.625 mg/MPA 2.5 mg	FG, OGTT	FG ↓, PG ↑
CE 0.45 mg/MPA 1.5 mg	FG, OGTT	FG ↓, PG ↑
CE 0.3 mg/MPA 1.5 mg	FG, OGTT	FG ←→ PG ←→
Hodis (79)	RCT	222	45+	2 y	o-E2 1 mg	HbA1c	HbA1c ↓ 2.4%
Salpeter (6)	Meta-analysis	33,315	60 ± 6	0.15–5 y	Variable		IR ↓ 13%
RCTs	HOMA-IR	Diabetes ↓ 30%
NHS (80)	OS	21,028	30–55	12 y	Variable	Self report record	Diabetes ↓ 20%
E3N (81)	OS	63,624	40–65	10 y	Variable	Self report record	Diabetes ↓ 25%
RBS (31)	OS	785	50–97	8 y	Variable	FG	FG ↓
Pentti (82)	OS	8483	52–62	5 y	Variable	Record	Diabetes ↓ 69%
Xu (83)	Meta-analysis	16,807	49–70	5–12 y	Variable	HbA1c, FG	FG ↓, HbA1c ↓
Women With Type 2 Diabetes
Friday (84)	RCT	25	50–77	8 wk	CE 0.625 mg	HbA1c	HbA1c ↓
FG and insulin	IR ↓
Anderson (85)	RCT	27	40–65	3 mo	o-E2 2 mg	HbA1c	HbA1c ↓
FG and insulin	IR ↓
Brussaard (86)	RCT	40	61 ± 5	6 wk	o-E2 2 mg	HbA1c, euglycemic, hyperinsulinemic clamp	HbA1c ↓
HGP ↓
Salpeter (6)	Meta-analysis RCTs	33,315	60 ± 6	0.15–5 y	Variable	HOMA-IR	IR ↓ 33%

Name

Design

Population

Age (y)

Treatment Length

MHT

Technique

Effect^a

Women Without Diabetes

PEPI (2)

RCT

788

45–64

3 y

CE 0.625 mg ± progestin

FG, fasting insulin

IR ↓

HERS (3)

RCT

2029

67 ± 7

4.1 y

CE 0.625 mg/MPA 2.5 mg

Incident diabetes FG

Diabetes ↓ 35%

WHI (4, 5, 87)

RCT

15,641

50–79

5.6 y

CE 0.625 mg/MPA 2.5 mg

Self-report

Diabetes ↓ 19%–21%

10,739

50–79

7.1 y

CE 0.625 mg

Self-report

Diabetes ↓ 12%–14%

KEEPS (77)

RCT

727

42–58

4 y

CE 0.45 mg/o-P4 200 mg

HOMA-IR

IR ↓

t-E2 50 µg/o-P4 200 mg

HOMA-IR

IR ↓ (ns)

Lobo (78)

RCT

745

40–65

1 y

CE 0.625 mg/MPA 2.5 mg

FG, OGTT

FG ↓, PG ↑

CE 0.45 mg/MPA 1.5 mg

FG, OGTT

FG ↓, PG ↑

CE 0.3 mg/MPA 1.5 mg

FG, OGTT

FG ←→ PG ←→

Hodis (79)

RCT

222

45+

2 y

o-E2 1 mg

HbA1c

HbA1c ↓ 2.4%

Salpeter (6)

Meta-analysis

33,315

60 ± 6

0.15–5 y

Variable

IR ↓ 13%

RCTs

HOMA-IR

Diabetes ↓ 30%

NHS (80)

21,028

30–55

12 y

Variable

Self report record

Diabetes ↓ 20%

E3N (81)

63,624

40–65

10 y

Variable

Self report record

Diabetes ↓ 25%

RBS (31)

785

50–97

8 y

Variable

FG ↓

Pentti (82)

8483

52–62

5 y

Variable

Record

Diabetes ↓ 69%

Xu (83)

Meta-analysis

16,807

49–70

5–12 y

Variable

HbA1c, FG

FG ↓, HbA1c ↓

Women With Type 2 Diabetes

Friday (84)

RCT

50–77

8 wk

CE 0.625 mg

HbA1c

HbA1c ↓

FG and insulin

IR ↓

Anderson (85)

RCT

40–65

3 mo

o-E2 2 mg

HbA1c

HbA1c ↓

FG and insulin

IR ↓

Brussaard (86)

RCT

61 ± 5

6 wk

o-E2 2 mg

HbA1c, euglycemic, hyperinsulinemic clamp

HbA1c ↓

HGP ↓

Salpeter (6)

Meta-analysis RCTs

33,315

60 ± 6

0.15–5 y

Variable

HOMA-IR

IR ↓ 33%

Name	Design	Population	Age (y)	Treatment Length	MHT	Technique	Effect^a
Women Without Diabetes
PEPI (2)	RCT	788	45–64	3 y	CE 0.625 mg ± progestin	FG, fasting insulin	IR ↓
HERS (3)	RCT	2029	67 ± 7	4.1 y	CE 0.625 mg/MPA 2.5 mg	Incident diabetes FG	Diabetes ↓ 35%
WHI (4, 5, 87)	RCT	15,641	50–79	5.6 y	CE 0.625 mg/MPA 2.5 mg	Self-report	Diabetes ↓ 19%–21%
10,739	50–79	7.1 y	CE 0.625 mg	Self-report	Diabetes ↓ 12%–14%
KEEPS (77)	RCT	727	42–58	4 y	CE 0.45 mg/o-P4 200 mg	HOMA-IR	IR ↓
t-E2 50 µg/o-P4 200 mg	HOMA-IR	IR ↓ (ns)
Lobo (78)	RCT	745	40–65	1 y	CE 0.625 mg/MPA 2.5 mg	FG, OGTT	FG ↓, PG ↑
CE 0.45 mg/MPA 1.5 mg	FG, OGTT	FG ↓, PG ↑
CE 0.3 mg/MPA 1.5 mg	FG, OGTT	FG ←→ PG ←→
Hodis (79)	RCT	222	45+	2 y	o-E2 1 mg	HbA1c	HbA1c ↓ 2.4%
Salpeter (6)	Meta-analysis	33,315	60 ± 6	0.15–5 y	Variable		IR ↓ 13%
RCTs	HOMA-IR	Diabetes ↓ 30%
NHS (80)	OS	21,028	30–55	12 y	Variable	Self report record	Diabetes ↓ 20%
E3N (81)	OS	63,624	40–65	10 y	Variable	Self report record	Diabetes ↓ 25%
RBS (31)	OS	785	50–97	8 y	Variable	FG	FG ↓
Pentti (82)	OS	8483	52–62	5 y	Variable	Record	Diabetes ↓ 69%
Xu (83)	Meta-analysis	16,807	49–70	5–12 y	Variable	HbA1c, FG	FG ↓, HbA1c ↓
Women With Type 2 Diabetes
Friday (84)	RCT	25	50–77	8 wk	CE 0.625 mg	HbA1c	HbA1c ↓
FG and insulin	IR ↓
Anderson (85)	RCT	27	40–65	3 mo	o-E2 2 mg	HbA1c	HbA1c ↓
FG and insulin	IR ↓
Brussaard (86)	RCT	40	61 ± 5	6 wk	o-E2 2 mg	HbA1c, euglycemic, hyperinsulinemic clamp	HbA1c ↓
HGP ↓
Salpeter (6)	Meta-analysis RCTs	33,315	60 ± 6	0.15–5 y	Variable	HOMA-IR	IR ↓ 33%

Table 1.

Open in new tab

Effect of MHT on Type 2 Diabetes Risk

Name	Design	Population	Age (y)	Treatment Length	MHT	Technique	Effect^a
Women Without Diabetes
PEPI (2)	RCT	788	45–64	3 y	CE 0.625 mg ± progestin	FG, fasting insulin	IR ↓
HERS (3)	RCT	2029	67 ± 7	4.1 y	CE 0.625 mg/MPA 2.5 mg	Incident diabetes FG	Diabetes ↓ 35%
WHI (4, 5, 87)	RCT	15,641	50–79	5.6 y	CE 0.625 mg/MPA 2.5 mg	Self-report	Diabetes ↓ 19%–21%
WHI (4, 5, 87)	RCT	10,739	50–79	7.1 y	CE 0.625 mg	Self-report	Diabetes ↓ 12%–14%
KEEPS (77)	RCT	727	42–58	4 y	CE 0.45 mg/o-P4 200 mg	HOMA-IR	IR ↓
KEEPS (77)	RCT	727	42–58	4 y	t-E2 50 µg/o-P4 200 mg	HOMA-IR	IR ↓ (ns)
Lobo (78)	RCT	745	40–65	1 y	CE 0.625 mg/MPA 2.5 mg	FG, OGTT	FG ↓, PG ↑
					CE 0.45 mg/MPA 1.5 mg	FG, OGTT	FG ↓, PG ↑
					CE 0.3 mg/MPA 1.5 mg	FG, OGTT	FG ←→ PG ←→
Hodis (79)	RCT	222	45+	2 y	o-E2 1 mg	HbA1c	HbA1c ↓ 2.4%
Salpeter (6)	Meta-analysis	33,315	60 ± 6	0.15–5 y	Variable		IR ↓ 13%
Salpeter (6)	RCTs	33,315	60 ± 6	0.15–5 y	Variable	HOMA-IR	Diabetes ↓ 30%
NHS (80)	OS	21,028	30–55	12 y	Variable	Self report record	Diabetes ↓ 20%
E3N (81)	OS	63,624	40–65	10 y	Variable	Self report record	Diabetes ↓ 25%
RBS (31)	OS	785	50–97	8 y	Variable	FG	FG ↓
Pentti (82)	OS	8483	52–62	5 y	Variable	Record	Diabetes ↓ 69%
Xu (83)	Meta-analysis	16,807	49–70	5–12 y	Variable	HbA1c, FG	FG ↓, HbA1c ↓
Women With Type 2 Diabetes
Friday (84)	RCT	25	50–77	8 wk	CE 0.625 mg	HbA1c	HbA1c ↓
Friday (84)	RCT	25	50–77	8 wk	CE 0.625 mg	FG and insulin	IR ↓
Anderson (85)	RCT	27	40–65	3 mo	o-E2 2 mg	HbA1c	HbA1c ↓
Anderson (85)	RCT	27	40–65	3 mo	o-E2 2 mg	FG and insulin	IR ↓
Brussaard (86)	RCT	40	61 ± 5	6 wk	o-E2 2 mg	HbA1c, euglycemic, hyperinsulinemic clamp	HbA1c ↓
Brussaard (86)	RCT	40	61 ± 5	6 wk	o-E2 2 mg	HbA1c, euglycemic, hyperinsulinemic clamp	HGP ↓
Salpeter (6)	Meta-analysis RCTs	33,315	60 ± 6	0.15–5 y	Variable	HOMA-IR	IR ↓ 33%

Name	Design	Population	Age (y)	Treatment Length	MHT	Technique	Effect^a
Women Without Diabetes
PEPI (2)	RCT	788	45–64	3 y	CE 0.625 mg ± progestin	FG, fasting insulin	IR ↓
HERS (3)	RCT	2029	67 ± 7	4.1 y	CE 0.625 mg/MPA 2.5 mg	Incident diabetes FG	Diabetes ↓ 35%
WHI (4, 5, 87)	RCT	15,641	50–79	5.6 y	CE 0.625 mg/MPA 2.5 mg	Self-report	Diabetes ↓ 19%–21%
WHI (4, 5, 87)	RCT	10,739	50–79	7.1 y	CE 0.625 mg	Self-report	Diabetes ↓ 12%–14%
KEEPS (77)	RCT	727	42–58	4 y	CE 0.45 mg/o-P4 200 mg	HOMA-IR	IR ↓
KEEPS (77)	RCT	727	42–58	4 y	t-E2 50 µg/o-P4 200 mg	HOMA-IR	IR ↓ (ns)
Lobo (78)	RCT	745	40–65	1 y	CE 0.625 mg/MPA 2.5 mg	FG, OGTT	FG ↓, PG ↑
					CE 0.45 mg/MPA 1.5 mg	FG, OGTT	FG ↓, PG ↑
					CE 0.3 mg/MPA 1.5 mg	FG, OGTT	FG ←→ PG ←→
Hodis (79)	RCT	222	45+	2 y	o-E2 1 mg	HbA1c	HbA1c ↓ 2.4%
Salpeter (6)	Meta-analysis	33,315	60 ± 6	0.15–5 y	Variable		IR ↓ 13%
Salpeter (6)	RCTs	33,315	60 ± 6	0.15–5 y	Variable	HOMA-IR	Diabetes ↓ 30%
NHS (80)	OS	21,028	30–55	12 y	Variable	Self report record	Diabetes ↓ 20%
E3N (81)	OS	63,624	40–65	10 y	Variable	Self report record	Diabetes ↓ 25%
RBS (31)	OS	785	50–97	8 y	Variable	FG	FG ↓
Pentti (82)	OS	8483	52–62	5 y	Variable	Record	Diabetes ↓ 69%
Xu (83)	Meta-analysis	16,807	49–70	5–12 y	Variable	HbA1c, FG	FG ↓, HbA1c ↓
Women With Type 2 Diabetes
Friday (84)	RCT	25	50–77	8 wk	CE 0.625 mg	HbA1c	HbA1c ↓
Friday (84)	RCT	25	50–77	8 wk	CE 0.625 mg	FG and insulin	IR ↓
Anderson (85)	RCT	27	40–65	3 mo	o-E2 2 mg	HbA1c	HbA1c ↓
Anderson (85)	RCT	27	40–65	3 mo	o-E2 2 mg	FG and insulin	IR ↓
Brussaard (86)	RCT	40	61 ± 5	6 wk	o-E2 2 mg	HbA1c, euglycemic, hyperinsulinemic clamp	HbA1c ↓
Brussaard (86)	RCT	40	61 ± 5	6 wk	o-E2 2 mg	HbA1c, euglycemic, hyperinsulinemic clamp	HGP ↓
Salpeter (6)	Meta-analysis RCTs	33,315	60 ± 6	0.15–5 y	Variable	HOMA-IR	IR ↓ 33%

Abbreviations: FG, fasting glucose; GTT, glucose tolerance test; IR, insulin resistance; NHS, Nurses’ Health Study; ns, nonsignificant; o-E2, oral micronized E2; o-P4, oral micronized progesterone; OS, observational study; PEPI, Postmenopausal Estrogen/Progestin Interventions study; PG, postchallenge glucose; RBS, Rancho Bernardo Study; t-E2, transdermal E2.

In the Effect column, up and down arrows indicate increase and decrease, respectively.

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