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Perimenopause

Pathophysiology

Perimenopause is the transitional period that occurs prior to menopause (1,2, 3). During this period, hormonal changes and biological changes occur (1,2,3). These changes may start to occur 2 to 8 years before menopause and eventually lead to irregular menstrual cycles, an increase in cycle interval or a decrease in cycle length (1). In this transitional period, women may also experience physical symptoms that are similar in nature to menopausal symptoms, primary vasomotor symptoms and they may necessitate treatment (1).

The pathophysiological changes that occur during perimenopause are due to the decrease and the gradual but eventual loss of the activity of the ovarian follicles (1,2). When women age, the number of the ovarian follicles decreases (1). The follicles that remain require higher levels of FSH for maturation and ovulation (1). In perimenopause, the FSH concentrations lead to irregular and unpredictable menses as the concentrations tend to rise during some menstrual cycles, but fall during subsequent menstrual cycles (1). Ovaries are responsible for producing estrogen, progesterone and androgens (1). The fluctuation in the estrogen levels is responsible for the vasomotor symptoms, psychological symptoms and disturbances of sexuality (1). In general, the symptoms of perimenopause are due to hormonal fluctuations and the onset of an estrogen-deficient state (1,2).

Clinical Presentation

Some signs and symptoms include: vasomotor symptoms (hot flashes, night sweats), irregular menses, episodic amenorrhea, sleep disturbances, mood swings, vaginal dryness, and depression (1,3,4).

Diagnosis

The menopausal transition period is denoted by a variation in the menstrual cycle length and an elevated serum FSH concentration and finishes with the final menstrual period (which is not recognized until after 12 months of amenorrhea) (5). Perimenopause occurs in the early stage of the menopausal transition, which is characterized by variable cycle length (> 7 days different from normal menstrual cycle length, which is 21 to 35 days) (5). Lab tests are not usually required for the diagnosis of perimenopause (3). The present of symptoms and the patient’s age can be used to establish the diagnosis (5). FSH levels are intermittent in perimenopause and cannot be relied upon for testing (5). Estrogen levels are unreliable and can be quite variable as well, so it is not recommended for a diagnosis tool in perimenopause (5). The average age of menopause is 51 and perimenopausal changes may start to occur 2 to 8 years before (1,2).

Prognosis

Perimenopause will eventually lead up to menopause (1,2). This is not a disease, but a natural event that signifies the transition from the reproductive to the non reproductive years (3). It is the end of fertility, which results from the decreased production of sex hormones estrogen and progesterone from the ovaries (3). The estrogen deficiency that comes with menopause may contribute to the develop of diseases such as osteoporosis, decreased levels of HDL, increased LDL, increased triglyceride levels and also an increase incidence of cardiovascular disease (1,2,4). The symptoms of hot flashes are finite in duration and these do not last forever (5). Estrogen has a protective effect on the bone by inhibiting the resportion (5). The decrease in estrogen production due to menopause will cause an increase in osteoclast activity and decrease bone formation, which will increase the risk of fracture (1,2,3). It is estimated that >50% of the total amount of bone loss that occurs in women take place within the first few years of menopause (3). Postmenopausal women experience an accelerated rate of bone loss that lasts for 5 to 7 years (1,2,3). A 3% to 5% of bone loss occurs per year (1,2,3). The maximum amount of vasomotor symptoms occurs within the first 2 years after the last period and the frequency of these symptoms will gradually decrease over 6 years (4). Vaginal symptoms will start a few years after the menstrual period, however, vaginal atrophy does not improve over time (4).

Monitoring

During perimenopause, if a patient presents with irregular bleeding, she should have endometrial sampling (endometrial biopsy or dilation and curettage) to rule out endometrial cancer (3).

The use of estrogen with or without progestin for the purpose of treating menopausal symptoms should be reassessed annually to determine if continued use will produce a greater benefit than risk (3,4,5). This is because long term HRT outweigh the benefits for the average healthy postmenopausal women, as it is associated with an increase risk of stroke compared to placebo, and does not prevent coronary heart disease (3,4). Furthermore, the WHI study showed increase risk of venous thromboembolism, myocardial infarction, stroke, and breast cancer while on HRT (3,4). The risk of VTE was 3.6 times higher with estrogen-progestin therapy in the first year of use compared to placebo (3,4). The results of the WHI suggest that the cardiac risk increases when the HRT is initiated further away from the onset of menopause and the risk is higher with increased age when starting HRT (3,4). A systemic review has found that estrogen plus progesterone and estrogen alone reduce the frequency and severity of hot flashes in postmenopausal women significantly (3,4). Further systemic reviews and RCTs have found that estrogen improves urogential symptoms, sleep disturbance, physical functioning and quality of life in menopausal women (3,4).

The benefits of short term HRT may outweigh the risk (3,4). It is the most effective treatment for hot flashes, night sweats, and vaginal discomfort (3,4) Specifically, patients who are on long term HRT should have a reassessment of their therapy to see if cessation, reduction in dose, changes in the delivery system is possible (3,4). The lowest effective dose for the shortest duration should be prescribed (3,4).

References

  1. Chisholm-Burns MA, Wells BG, Schwinghammer TL, Malone PM, Kolesar JM, Rotschafer JC, Dipiro JT. Pharmacotherapy: Principles and Practice. McGraw-Hill: 2008. p. 766-773
  2. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy: A Pathophysiologic Approach, 7th ed. New York: McGraw-Hill; 2007. p. 1351-63
  3. Hull AD, Fife RS, Baustian GH, Murray JL. Menopause. MD Consult [online]. Maryland Heights MO: Elsevier Inc. 2011 [cited 2011 Nov 6]. Available from: www.mdconsult.com
  4. Repchinsky C, editor-in-chief. Therapeutic Choices. 6th ed. Canadian Pharmacists Association; 2011. p. 943.
  5. Martin KA, Barbieri RL. Postmenopausal hormone therapy: Benefits and risks. Up to Date [Internet]. 2011 [updated 2011; cited 2011 Nov 6]. Available from: http:// //http://www.uptodate.com// =Disclaimer= This information is presented for informational purposes only and is not meant to be a substitute for advice provided by qualified health care professionals. You should contact your qualified health care provider if you have or suspect any health problems. This article is not intended to provide medical advice for its readers //

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