Hormonal changes in menopause: Is it all downhill from here?

The last several weeks, this blog has discussed hormones during the reproductive cycle  as well as neuro-endo connections (e.g.  serotonin, estradiol, testosterone, dopamine, progesterone, and GABA).  This week we will look at hormonal changes approaching menopause.

Figure 1. As women age, ovarian reserve falls, eventually leading to hormone fluctuations and the onset of menopause.

Around age 38 the ovarian reserve declines rapidly significantly decreasing fertility (Figure 1).  At this point, there are far fewer follicles that can be recruited and, as a result, less egg maturation and release.  This ovarian depletion results in hormonal fluctuation.  All of this eventually leads up to a woman’s final menstrual period, which is on average around age 51.

The first hormone to begin decreasing during perimenopause is progesterone (Figure 2).  As the number of follicles decreases, ovulation and the resulting corpus luteum formulation occurs less frequently. This significantly decreases the amount of progesterone produced. As progesterone levels begin to fall, gonadotropin releasing hormone (GnRH) increases, and as a result, follicle stimulating hormone (FSH) increases in an attempt to recruit a follicle. At the onset of menopause, when ovarian reserve is almost completely diminished, estradiol levels decrease dramatically and estrone becomes the most abundant type of estrogen in the body.

Figure 2. Progesterone is the first hormone to decrease during perimenopause followed by an increase in FSH and then a decrease in estradiol (E2).

Although progesterone and estrogen levels fall drastically, hormone synthesis doesn’t stop altogether during menopause. When the ovarian reserve is depleted, and the ovaries are no longer producing hormones, other tissues in the body become the main producers of hormones. The adrenal glands are one of these tissues. They produce progesterone and androstenedione, the precursor to testosterone. Some of this testosterone converts into estrogen.

Adrenal fatigue or burnout can cause additional issues for women in perimenopause as exhausted adrenals cannot synthesize as many hormones as healthily functioning adrenals. Adipose (fat) tissue also produces estrogen. Individuals with higher body mass indexes (BMIs) and more adipose tissue have higher circulating hormone levels.

While it is natural for hormone levels to change throughout perimenopause and menopause, patients entering menopause with healthy adrenal gland activity and normal adipose stores have any easier transition with fewer symptoms. It is also important to keep in mind that with hormonal changes neurotransmitter activity also changes adding another layer to supporting a healthy transition to menopause.

References:

Nussey, Stephen, and Saffron Whitehead. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific, 2001.

Widmaier, et al. (2008). Vander’s Human Physiology; Eleventh Edition.