Perimenopausal

Being perimenopausal (“around the menopause”) denotes the period of life directly preceding and directly following menopause (Pic. 1), or permanent cessation of menstrual cycles. Women usually start this period at a mean age of 45.5 to 47.5 years. In contrast, pre-menopause refers only to the period preceding menopause, whereas peri-menopause includes the period following it. Due to declining hormonal activity of the ovaries, menstrual cycles get progressively longer, until they stop completely. The women may also experience a number of symptoms related to the ongoing hormonal changes.

During perimenopause, estrogen (the primary female sex hormone) levels gradually decrease, but often have wide fluctuations. These fluctuations cause many of the physical changes during perimenopause as well as during menopause. Some of these changes are hot flashes, night sweats, difficulty sleeping, vaginal dryness or atrophy, incontinence, osteoporosis, and heart disease.

In some women, menopause may bring about a sense of loss related to the end of fertility. During this period, fertility diminishes but is not considered to reach zero until the official date of menopause. The official date is determined retroactively, once 12 months have passed after the last menstrual bleeding.

It is possible that the timing of menopause may be influenced by different factors such as cigarette smoking, living at high altitudes and history of depression. The majority of perimenopausal women experience irregular menstrual periods, when shortened cycles or longer periods of amenorrhea may reflect the large fluctuation of the ovarian estrogen secretion observed during this time. 

Consequently, confirmation of the perimenopause is usually based on laboratory tests and a woman's medical history, as well as on the characteristics of somatic and emotional symptoms she reports. 

Perimenopause is a natural stage of life. It is not a disease or a disorder. Therefore, it does not automatically require any kind of medical treatment. However, in those cases where the physical, mental, and emotional effects of perimenopause are strong enough that they significantly disrupt the life of the woman experiencing them, medical therapy may sometimes be appropriate.

Symptoms

Hormonal changes

Generally, the first apparent hormonal change of the perimenopause is a rising concentration of the pituitary gonadotropin FSH (follicle-stimulating hormone). The rising FSH concentration is probably caused by an exponential decline of gonadotropin-sensitive ovarian follicles as menopause approaches.

Menstrual pattern

During the transition to menopause, menstrual patterns can show shorter cycling (by 2–7 days); longer cycles remain possible. There may be irregular bleeding (lighter, heavier, spotting). Dysfunctional uterine bleeding is often experienced by women approaching menopause due to the hormonal changes that accompany the menopause transition. Spotting or bleeding may simply be related to vaginal atrophy, a benign sore (polyp or lesion), or may be a functional endometrial response.

Hot flushes

In addition to changes in the hormonal profile, the perimenopause is typically marked by the presence of vasomotor symptoms such as hot flushes and night sweats (hot flushes that occur with perspiration during sleep). These symptoms are experienced by 45-85% of women. The complete physiological mechanisms of hot flushes remain undetermined, however, it is hypothesised that they arise due to increased fluctuations of estrogen levels, which impair the thermoregulatory abilities of the organism. Nonetheless, some clinical studies suggest that estrogen administration (usually called Hormone replacement therapy) decreases the occurrence of hot flushes in a dose-dependent fashion. Hot flushes usually resolve some time after menopause in most women.

Associated diseases

Endometrial polyps

Endometrial polyps (Pic. 2) are localized, pedunculated or sessile tissue growths consisting of a variable amount of glands, stroma (connective tissue “scaffold”) and blood vessels, localized in the endometrium, the inner mucous lining of the uterine cavity. Endometrial polyps are reported to be most prevalent in the premenopausal period, generally between 40 and 50 years of age. Sometimes they ulcerate, bleed or twist, which may lead to partial or complete necrosis (tissue death) and may be the source of abnormal uterine bleeding. Endometrial polyps should also be pointed out as a risk factor for the presence of endometrial adenocarcinoma, which is nine times more frequent in patients with polyps than in patients with no polyps. Although infrequent, polyps can become malignant. To be considered a primary site of malignancy, the tumor must be confined to the apex, with no lesion in its base, as well as in the surrounding endometrium. 

Menopause

Menopause, also known as the climacteric, is the time in most women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause typically occurs between 49 and 52 years of age. 

Depression

The mechanism by which the perimenopause is associated with an increased risk for depressive symptoms in middle-aged women is still controversial. Most studies examining this question vary greatly in design. For example, data are derived from different settings (gynecological clinics versus community-based studies), and have included women with diverse menopausal status, ascribed primarily to age. These studies also suffered from a lack of standardized instruments for evaluating psychiatric symptoms. It is therefore more informative to review them separately.

Complications

Physiological changes and some physical manifestations associated with the transition to menopause include urogenital atrophy causing dyspareunia (painful sexual intercourse), dysfunctional uterine bleeding, and a higher risk for osteoporosis (loss of bone mass, leading to their increased fragility) and cardiovascular disease. These changes may account for the high frequency with which perimenopausal women seek medical consultation as compared to pre- or postmenopausal women.

Risk factors

Perimenopause is a natural phase in a woman’s life. However, perimenopausal changes and successive menopause may start at an earlier age in certain women. Known risk factors for an earlier perimenopause and menopause include:

• family history of earlier menopause
• smoking
• cancer treatment – chemotherapy, or radiotherapy in the pelvic region
• hysterectomy (surgical removal of the uterus)

Prevention

Perimenopause marks a significant decline in the woman’s fertility, as the ovaries are slowly depleting their oocyte reserve. Women undergoing perimenopause are usually significantly subfertile and may require methods of assisted reproduction, hormonal therapy, and in women over 45, usually also donor oocytes if they wish to get pregnant.

Women will often, but not always, start these transitions (perimenopause and menopause) about the same time as their mother did. After one year of amenorrhea (absent menstrual cycles), indicating the phase of postmenopause, women experience a well-defined profile of hormones, with low estrogen and progesterone, and high gonadotropin levels.