Dr. Di Pace, we often associate the concept of longevity only with maintaining cardiovascular or cognitive health, but there is much more to it. What does aging mean from a gynecological point of view?

When talking about aging, a crucial distinction must be made between the sexes: from a certain point in life onward, aging for a woman and for a man is very different. While in men aging is a gradual process, in women menopause marks a drastic turning point. The sudden drop in hormone production triggers a “storm” of physiological reactions. In the first ten years after the last menstrual period, women’s health is conditioned by an overlap between the effects of the estrogen decline and those of the passage of time.

Let’s talk about menopause, then. Sometimes it seems to be discussed as an event in its own right, a single moment in a woman’s life. But from what you have explained, it seems more like a process, and one of considerable duration. When and how is it correct to speak of menopause, then?

We need to dismantle the idea that menopause is a single event and that it occurs suddenly. The concept of menopause has expanded greatly today because women’s average lifespan has grown longer and about a third of their lifetime is now spent in this phase. From a clinical point of view, we define menopause as the absence of the menstrual cycle (amenorrhea) for at least 12 consecutive months, at an appropriate age, that is, around 50 years. However, it is not a simple “switch” that turns off: it is a gradual process. Hormonal changes, in fact, begin about 7–8 years before the last menstrual period. This phase, which includes premenopause and perimenopause, is characterized by certain signs, which, however, women often do not know about or do not connect with the passage of time.

What are these first “warning signs” that a woman should monitor?

The first sign is often a shortening of the menstrual cycle (for example, from 28 to 25 days) or the appearance of two periods in the same month. In this phase it is progesterone that begins to decline, but not estrogens, which can also cause a heavier flow. If these irregularities become systematic, it is a sign that the ovarian reserve is decreasing and a medical consultation is advisable, especially if the periods become very heavy. Another sign that menopause is approaching is metabolic change: weight gain and the redistribution of visceral fat typically begin 7 years before the last period and stabilize about 2 years after established menopause. In addition, when periods start to “skip”, the first hot flashes, sleep disturbances, anxiety, irritability or what we call “cognitive fog” (brain fog) may appear. Recognizing and monitoring these changes is very important both to avoid complications, such as anemia in the case of very heavy periods, and to start undergoing preventive tests such as bone densitometry (MOC) or cardiovascular screening, so as to build health for the decades that follow.

What, on the other hand, are the symptoms and signs of established menopause?

Besides the absence of periods and the classic hot flashes, a great many different symptoms are counted; some even say as many as 72. And the reason is that estrogen receptors are everywhere in the body. Neurological symptoms may occur, such as sleep disturbances, cognitive fog, anxiety, irritability; musculoskeletal problems, such as joint pain, “frozen shoulder” and osteoarthritis in the hands, due to the loss of estrogen protection on the tendons; aesthetic changes, including acne and hair thinning, an androgenic effect due to the fact that, in the absence of estrogens, the few androgenic (male) hormones become dominant.

The “intimate” disorders deserve a more detailed discussion: those that women themselves often consider taboo and accept as an inevitable consequence of the passing of time. They range from vaginal dryness to recurrent cystitis and to pain during sexual intercourse. The clinical term that covers them all is genitourinary syndrome of menopause and it is a complex condition that, as the name suggests, involves the genital and urinary systems, eventually also affecting sexual well-being. Once again, everything starts from the drop in estrogens: the tissues of the vulva and vagina are no longer reached by the action of these hormones and they atrophy, an effect also amplified by changes in the local microbiota, called the estrobolome. When vulvovaginal atrophy sets in, the tissues become thinner and less elastic, dryness appears and pain may occur during intercourse. All factors that can contribute to a decline in desire, impairing relationships. At the urinary level too, the hormonal deficiency weakens the mucous membranes, making women more prone to recurrent cystitis and incontinence.

I want to stress strongly, however, that there are solutions and that one must not resign oneself.

Speaking of possible treatments, what is the scientific landscape today?

A premise is needed: the approach is not limited to managing the symptoms of menopause, but enters the sphere of longevity medicine. In other words, we do not just want to make hot flashes disappear; we want to ensure that women age well, also taking care of the heart, bones and brain.

In this context, the most effective treatment is hormone replacement therapy (HRT), which acts both on symptoms and at the level of systemic prevention. Studies tell us that administering hormones to replace — precisely — the estrogens that are no longer produced by the body resolves hot flashes, insomnia, brain fog, etc., and that it reduces, for example, cardiovascular risk by acting as a vasodilator and improving the share of “good” cholesterol. Positive data are also reported regarding the prevention of osteoporosis and sarcopeniaThe term sarcopenia refers to the progressive loss of muscle mass and related decrease in strength; in addition to the volume reduction in muscle mass, it also leads to a worsening of the latter because:
• the muscle is slowly replaced by adipose tissue (fat),
• the junctions between muscle and nerve fibres (neuromuscular junction) tend to degenerate,
• muscle oxidative stress increases.
, that is, respectively, the disease resulting from the loss of bone density and the loss of muscle mass. In Italy, HRT still frightens many patients because it increases the risk of developing breast cancer. However, with the use of bioidentical hormones this increase is minimal: we are talking about 8 cases per 10,000 after 10 years of therapy. And on the other hand, in addition to the advantages already mentioned, the risk of colorectal cancer is reduced by 30%.

And can it be started at any time from menopause onward?

No, there is a so-called window of opportunity within which HRT is effective and safe. Therapy must be started within 10 years of the last menstrual period, and not beyond 60 years of age. Beyond these limits, the risks outweigh the benefits. I would add that it is a personalized treatment, tailored after a careful assessment of the patient’s general condition and also of her needs.

Are there alternatives for those who cannot or do not want to take hormones?

There are new non-hormonal drugs that act specifically on hot flashes and insomnia. They are effective, but they do not offer systemic protection like HRT. Herbal medicines are also an alternative, but they have only partial efficacy on symptoms (they reduce them by 40%) and they too do not offer long-term protection for bones and heart.

Read the second part of the interview with Dr. Di Pace here:

Sexuality in Menopause. Here Is How to Preserve and Restore Intimate Well-Being