1. The document presents a 7-stage system for classifying reproductive aging in women from pre-menopause to post-menopause. Stages -5 to -3 cover the reproductive years, -2 and -1 are the menopausal transition, and +1 and +2 are post-menopause.
2. Key aspects of each stage are defined, including menstrual cycles, fertility, hormone levels, symptoms, and ovarian ultrasound findings.
3. The new staging system provides standardized terminology and a framework for understanding a woman's progress through reproductive aging and menopause.
3. •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
4. •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
Aboubakr Elnashar
5. 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. Aboubakr Elnashar
6. 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
7. 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.
Aboubakr Elnashar
8. 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
11. 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).
Aboubakr Elnashar
12. 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.
Aboubakr Elnashar
13. •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.
Aboubakr Elnashar
14. 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
16. •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.
Aboubakr Elnashar
17. 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
19. 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.
Aboubakr Elnashar
20. 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
22. Symptoms of MT
Early:
• Cycle irregularity
• Vasomotor symptoms, breast tenderness, insomnia,
migraines, and premenstrual dysphoria.
Late:
• Genital atrophic symptoms
• Problems in sexual function
Aboubakr Elnashar
23. 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.
Aboubakr Elnashar
24. 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
Aboubakr Elnashar
25. •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
27. 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
30. 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