Health Resources: Health Articles

Menopause/Perimenopausal Transition

The perimenopausal period is the transition from reproductive years to menopause and can occur up to 10 years prior to a woman's last menstrual period. The hormonal changes during this transitional time are complex and include erratic estrogen production (both high and low), reduced ovarian follicle production of progesterone, and increased anovulatory cycles (cycles where an egg is not released).

Normal cycle basics:
Onset of menstrual flow to onset of next menstrual flow is 1 menstrual cycle. During menstrual flow, both estrogen and progesterone are at their lowest. The follicular phase begins with menstruation and typically lasts 10-14 days. Follicle Stimulating Hormone (FSH) levels rise causing maturation of several ovarian follicles and the size of the eggs triple. FSH also signals the ovaries to begin production of estrogen which stimulates Luteinizing Hormone (LH) levels to surge at around day 14 of cycle. The surge triggers one of the follicles to burst allowing the largest egg to be released (ovulation) into the fallopian tubes where it can be fertilized. This phase is followed by the premenstrual or luteal phase and lasts approximately 14 days. After ovulation, LH causes the corpus luteum to develop from the ruptured follicle and produce progesterone. Estrogen from the 1st half of the cycle primes the uterine lining and progesterone in the 2nd half develops the lining further for possible pregnancy. If there is no pregnancy, the corpus luteum disintegrates and progesterone levels drop to signal onset of the next menstrual period. The blood vessels in the uterine lining constrict at the ends cutting off the blood supply and causing sloughing of the uterine lining (menstrual flow).

Why is estrogen usually elevated in perimenopause?
FSH levels increase causing more follicles to be recruited than occurs during premenopausal years. Each of these recruited follicles makes a finite amount of estradiol. Together, these multiple recruited follicles produce the elevated follicular phase estradiol levels documented in perimenopause. This creates an "endogenous perimenopausal ovarian hyperstimulation" resulting in perimenopausal symptoms such as breast tenderness and enlargement, fluid retention, heavy, prolonged, or unpredictable menstrual bleeding, new onset of migraine headaches, and new or unpredictable mood swings.

Aren't hot flashes caused by low estrogen though?
The short answer is: No. More likely it is the extreme fluctuations of higher estrogen levels vs overall estrogen levels that cause vasomotor symptoms such as hot flashes and night sweats.

The Endocrine Society published a research review* that proposed 5 phases of perimenopausal transition including known hormonal changes and typical symptoms:

Phase A - regular and ovulatory cycles (egg released).

Symptoms:
  Increased breast tenderness, mood swings, fluid retention, and premenstrual symptoms.
  Shorter cycles (shortened follicular phase of cycle)
  Early morning night sweats (VMS = vasomotor symptoms) commonly are first experienced.
  Weight gain, migraine headaches, and abnormally heavy or flooding menstruation may occur.

Hormonally:
  Estradiol levels are at least intermittently high during this phase.
  FSH levels are intermittently in the early follicular phase (FP) but are usually normal.
  It is likely that inhibin levels would already be low. (Inhibin A & B are hormones made in the ovaries at different times during the menstrual cycle and tend to decrease FSH)

Phase B - basically regular cycles but disturbances of ovulation (such as short luteal phase, luteal phase insufficient, and anovulatory cycles) become more common.

Symptoms:
  Episodes of heavy flow may occur
  Increased premenstrual symptoms and menstrual cramps
  VMS may predictably return or increase in the days just prior to menstrual flow.

Hormonally:
  FSH is now intermittently elevated but still only during the early FP.
  LH continues to be normal and estradiol is often high.
  Inhibin levels are probably inappropriately low.

Phase C - unpredictable flow and alternating short and long or skipped cycles.

Symptoms:
  VMS tend to begin to occur more commonly during the waking hours during this phase of the transition,
   although most women will have minor symptoms.
  For some women, night VMS become more persistent but continue to be cyclic before flow and may still
   predict flow in some cycles.

Hormonally:
  FSH levels are usually at least slightly elevated.
  Estradiol levels are intermittently quite high but may also be normal and sometimes low.
  LH levels may occasionally be increased during this phase.
  Inhibin levels are low.

Phase D - onset of oligomenorrhea (menstrual periods occurring at intervals > 35 days)

Symptoms & hormones:
  More VMS, but may yet have times of high estrogen signs and symptoms after longer periods without
   flow.
  Ovulation occurs less than 50% of the time and often has abnormally low progesterone levels, if it does
   occur.
  By this phase, flow is usually light but unpredictable. Heavy flow during one menstruation may predict
   the onset of oligomenorrhea.
  FSH is now persistently elevated and LH also becomes consistently increased. Inhibin levels are postulated
   to be clearly low.

Phase E - final menstrual period and includes the year after what is retrospectively defined as menopause by the WHO.

Symptoms:
  This is a time of increased intensity and frequency of VMS, although a few women who experienced them
   earlier may also find they disappear.
  Premenstrual type symptoms and cramps are usually less but sometimes occur without any subsequent
   flow.
  Breast, fluid, and mood symptoms decrease.

Hormonally:
  FSH and LH are high and estrogen levels low or normal.
  Inhibin levels are consistently low.

Bottom Line: No, you are NOT crazy. Hormones have many actions in the body far beyond reproduction. When there are significant and/or rapid shifts in the hormonal system, symptoms can be wide in range and significantly impact quality of life. Be assured there are a broad range of treatment options available to help ease the perimenopausal transition.

If you find you need help navigating this transition, please contact Dr. Miller to schedule an appointment today (415) 785-3347. A one-time 15 minute pre-screening with Dr. Miller is available at no charge to determine if her services are right for you.

*Reference: Endocrine Reviews 19 (4): 397-428 1998