Benha University Hospital, Egypt

Email:elnashar1953@yahoo.com

Aboubakr Elnashar

Aboubakr Elnashar

•While there is a useful staging system for

puberty (Tanner/Marshall system),

a similar staging system for late

reproductive function has not been

developed.

•Confusion & duplication in the

nomenclature of the reproductive aging e.g.

climactric, perimenopause

Aboubakr Elnashar

•The American Society for Reproductive

Medicine (ASRM)

•The National Institute on Aging (NIA)

•The North American Menopause Society (NAMS)

Cosponsored a workshop to

•develop a relevant & useful staging system

•revise the nomenclature

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Definition

Aging:

The natural progression of changes in structure and

function that occur with the passage of time in the

absence of known disease.

Reproductive aging:

•A natural process that begins at birth and proceeds as

a continuum.

•It is a process and not an event, and the end

(menopause) is much easier to define than the

beginning.

Chronological age is a very poor indicator of

reproductive aging.

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Etiology

•Oocyte depletion in the ovary.

•Reproductive aging consists of a steady loss of

oocytes through atresia or ovulation, which does not

necessarily occur at a constant rate.

•The relatively wide age range (42–58 years) for

menopause in normal women indicate that either

- Wide variation in number of follicles at birth or

-Wide variation in the rate of oocyte loss

Aboubakr Elnashar

The workshop concentrated on developing a staging

system for all healthy women who age spontaneously

to a natural menopause.

The purpose of a staging system

To identify what point a given woman has reached in

the process of reproductive aging.

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The anchor for the staging system

is the final menstrual period (FMP).

The staging system has 7 stages; 5

precede and 2 follow the final menstrual period.

Stages -5 to -3 encompass the reproductive interval;

Stages -2 and -1 are the menopausal transition; and

Stages +1 and +2 are the postmenopause.

Aboubakr Elnashar

Aboubakr Elnashar

Aboubakr Elnashar

There is no demarcation between stages -5 to -3, since

fertility increases & decreases gradually over many

years.

Menstrual cycles:

After menarche (entry into stage -5) it usually takes

several years for regular menstrual cycles to become

established.

Menstrual periods should then occur every 21 to 35

days for a number of years (stages -4 & -3).

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Fertility:

•A woman’s peak fertility occurs in her mid- to late

twenties, after which it progressively decreases until

menopause (stage -4 to -1).

•Loss of fertility is the first sign of reproductive aging

that precedes the monotropic increase in FSH and

changes in menstrual cyclicity.

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•Endocrine changes:

1. An elevated FSH level is the first measurable sign

of reproductive aging. This initial elevation in FSH

level is most prominent in the early follicular phase of

the cycle (between D2 and 5) The initial elevation in

the late reproductive stage -3 is subtle; while clinicians

often use 10 mIU/mL as the cutoff value.

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2. Estradiol:

FSH level should only be interpreted in the context of

a simultaneously measured E2.

In the late reproductive stage (stage -3), E2 level in the

early follicular phase is either normal or elevated. If it

is elevated, it can suppress what otherwise would be

an elevated FSH level

An E2 level 80 pg/ml is often considered to be

elevated.

Aboubakr Elnashar

Aboubakr Elnashar

•Menopause

The anchor point that is defined after 12 months of

amenorrhea following the FMP (Retrospective diagnosis)

•Perimenopause:

Literally means “about or around the menopause.” It begins at

the same time as the MT i.e. with stage -2 and ends 12 months

after the FMP.

•The climacteric

is a vague term that used synonymously with perimenopause.

The terms perimenopause and climacteric should be used only

with patients and in the lay press and not in scientific papers.

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Menopausal transition (MT):

Stage -2 (early) and -1 (late)

The MT

begins with variation in menstrual cycle length in a woman

who has a monotropic FSH rise &

ends with the FMP

The early MT (stage -2):

Menstrual cycles remain regular, but the duration changes by 7

days or more.

The late MT (stage-1):

2 or more skipped menstrual periods & at least one

intermenstrual interval of 60 days or more.

Aboubakr Elnashar

Aboubakr Elnashar

Endocrine changes in MT:

1. FSH levels gradually increase throughout MT, but

levels vary greatly.

FSH levels can vary from cycle to cycle & can be

falsely reassuring if they are low.

The increase in FSH early in MT is due to increased

negative feedback effects on the hypothalamus &

pituitary.

These effects may be reduced because of a decrease in

an ovarian inhibin factor rather than E2, as

previously believed.

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2. Estradiol:

Recent investigations suggest that a progressive, linear decline

in estrogen secretion does not occur during the MT.

In MT stage, the elevated FSH levels may lead to increased E2

production greater than seen in women under the age of 35

years (Santro et al, 1996).

3. Inhibin & activin:

A combination of decreased inhibin A & B & increased activin

may favor greater output of FSH in the absence of any

decrease (& perhaps an increase) in E2 production

Aboubakr Elnashar

Aboubakr Elnashar

Symptoms of MT

Early:

• Cycle irregularity

• Vasomotor symptoms, breast tenderness, insomnia,

migraines, and premenstrual dysphoria.

Late:

• Genital atrophic symptoms

• Problems in sexual function

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Ovarian sonography in MT

1. The number of antral follicle (2–10 mm)

-Does not vary over the menstrual cycle

-Correlates well with chronological age

-Before the age of 37 years, the antral follicle count

showed a mean yearly decline of 4.8%, compared

with 11.7% thereafter (Scheffer et al,1999). -Clearly related to reproductive age and reflect the size

of the remaining primordial follicle pool.

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2. Ovarian volume:

•A strong direct relationship between ovarian volume

and the number of primordial follicles remaining in

the ovaries.

•Follicle decline with age

Wallace & Kelsey (Drs of Computer Sciences),

developed a technique for measuring a woman’s

‘bioclock’ (Hum Rep, 2004).

They applied mathematical and computer

models/analysis to find out the follicle population

decline for women entering the menopause early or

late

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•The measurement of ovarian volume by TVS will

enable

1. An accurate prediction of the age of menopause and

hence a woman’s reproductive age.

2. Estimate accurately how many follicles are left and

therefore what is the woman’s ‘reproductive age..

•Assisted conception, •Treatment for childhood cancer and

•women who may want to delay a family for personal

or professional reasons.

Aboubakr Elnashar

Aboubakr Elnashar

Stage +1 (early) postmenopause

defined as 5 years since the FMP. Stage +1 was further

subdivided into

segment “a”, the first 12 months after the FMP, and

segment “b”, the next 4 years.

Stage +2 (late postmenopause) has a definite

beginning but its duration varies, since it ends with

death.

Aboubakr Elnashar

Aboubakr Elnashar

Aboubakr Elnashar

1. Stages of reproductive aging are seven:

Five stages precede and two follow the final menstrual

period.

Stages -5 to -3 encompass the reproductive interval;

Stages -2 and -1 are the menopausal transition; and

Stages +1 and +2 are the postmenopause.

2. The reproductive staging system is a distinct

improvement in reproductive health.

3. These definitions are currently the best description

of reproductive aging but are subject to modification

as more knowledge becomes available

Aboubakr Elnashar

Aboubakr Elnashar