Menopause:Menopause:a natural eventa natural event

Henry Burger

Relationships between different time Relationships between different time periods surrounding the menopauseperiods surrounding the menopause

International Position Paper: Women’s Health and Menopause, NIH (2002)

Final menstrual period (FMP)Menopause

Postmenopause

Perimenopause

Menopausal transition

Climacteric

Mean age51 years

1 yearlater

Women in Block's study

Women from the present study with regular menses

Postmenopausal women

Perimenopausal women

Richardson et al. JCEM 1987

Ovarian follicle numbers with ageOvarian follicle numbers with age

BB

BB

B

J

F

FF

F

F

F

F

Age (years)

1

10

100

1000

10000

100000

0

0 10 20 30 40 50 60

Pri

mo

rdia

l fo

llic

les/

ova

ry

GnRH

Inhibin

Pituitary

Gonadotropins: - LH, FSH

Steroids

HypothalamusFeedbackhormones

Hypothalamo-pituitary ovarian Hypothalamo-pituitary ovarian axisaxis

Ovary

Log (inhibin B)

5.04.54.03.53.02.52.01.5

Lo

g (

FS

H)

4.5

4.0

3.5

3.0

2.5

2.0

1.5

Burger HG et al. Climacteric 2000

Relationships betweenRelationships betweenFSH and inhibin BFSH and inhibin B

< 40 years of age

> 40 years of age

Geometric mean annual hormone Geometric mean annual hormone levels relative to date of final menseslevels relative to date of final menses

*

Burger HG et al. JCEM 1999

0

10

20

30

40

50

60

-4 -3 -2 -1 0 1 2 3 4 5

Years around menopause

Inh

ibin

A (

ng

/l)

0

10

20

30

40

50

60

Inh

ibin

B (

ng

/l)

0

50

100

150

200

250

300

-4 -3 -2 -1 0 1 2 3 4 5

Est

rad

iol

(pm

ol/

l)

0

20

40

60

80

100

120

FS

H (

IU/l

)

(InhB)(InhA)

41%36%

71%43%

62%57%

80%65%

80%80%

78%78%

94%94%

* Percent of samples with undetectable inhibin

AndrogensAndrogensin the menopausal transitionin the menopausal transition

• In normal women, there is a 50% decrease in circulating concentrations of testosterone and dehydroepiandrosterone sulfate (DHEAS) from age 20 to age 451,2

• There is little if any decline in testosterone during the transition2,3

• DHEAS levels continue to fall with age, with no specific association with the transition

• The medical ‘myth’ that menopause is associated with an acute drop in androgens does not appear to be tenable any longer

1Zumoff 1995, 2Davison 2005; 3Burger 2000

Other endocrine featuresOther endocrine features

• Loss of LH response to an estradiol challenge in the perimenopause1,2

• Predominant circulating estrogen in reproductive life is estradiol, secreted by the ovary; postmenopausally it is estrone, produced by peripheral androgen aromatization3

• Anti-Müllerian hormone (also called Müllerian inhibiting substance), a member of the TGF super family and a product of preantral and small antral follicles, is under investigation as a marker for the size of the ovarian follicle pool4 and a promising predictor for the occurrence of the transition5

1Van Look 1977; 2Weiss 2004; 3Maroulis 1976; 4Visser 2006; 5van Rooij 2004