A new study published in the Canadian Medical Association Journal is making headline news. The review by Dr. Lega et al. suggests hormone therapy should be recommended as first-line treatment for perimenopausal and menopausal-symptoms in women under 60. My reaction to this paper was FINALLY!
Finally, we are listening to and validating the concerns of women during their perimenopause and menopausal journey. The culture of hormone replacement therapy shifted significantly with the release of the Women’s Health Initiative study in 2002. Which in my opinion has deprived many women of the benefits of Hormone Replacement Therapy (HRT). Women were deprived of evidence-based treatments and suffered unnecessarily from the symptoms of perimenopause which include hot flashes, night sweats, mood changes, weight gain, and loss of libido. Further, women lost out on the benefits of HRT in maintaining bone density, preventing osteopenia or osteoporosis and the resultant fractures.
Also, we know the risk of cardiovascular disease increases in postmenopausal women, primarily attributed to a decline in estrogen levels resulting in reduced vasodilation, impaired lipid profiles, increased inflammation, and diminished endothelial function. By depriving women of HRT there was a lost opportunity for cardiovascular and cerebrovascular protection. The article provides a great summary of the benefit and risk profiles for hormones, so I think it is an important read. However, I did have some critiques. The authors fail to distinguish between bioidentical vs. synthetic hormones and use terms such as estrogen, estradiol, and progestin with progesterone interchangeably which is problematic. Hormones are complicated and there are vocabulary nuances that women need to understand to truly analyze the research, safe to say progestin doesn’t equal progesterone and estrogen doesn’t equal estradiol. The article also focuses primarily on what we already know: Hormones are approved, work well, and are safe for the treatment of vasomotor symptoms of perimenopause and menopause. And while I’m glad we’re continuing to reinforce these ideas and help empower women to make informed decisions regarding the management of perimenopause and menopause, I hope with future research we can start to come to a better consensus on the potential preventative health benefits of hormone supplementation in healthy perimenopausal/postmenopausal women.
If you want to check out the article it can be found here: https://www.cmaj.ca/content/195/19/E677
Menstrual Cycle, Perimenopause and Menopause: What is Happening with our hormones?
Research has suggested 1 in 3 women do not understand their own menstrual cycle (2). Women need to understand their menstrual cycle to understand symptoms they are experiencing, and to be empowered to take charge of their own healthcare. So here is a crash course in the menstrual cycle and how that cycle is disrupted in perimenopause and menopause, which results in the common symptoms of transition.
The menstrual cycle involves a complex interplay of hormones, including estrogen, progesterone, Follicle-stimulating Hormone (FSH), and Luteinizing Hormone (LH). These hormones work together to control the development and release of eggs from the ovaries, prepare the uterus for potential pregnancy, and to regulate menstruation.
- Estrogen: During the first half of the cycle (follicular phase), estrogen levels gradually increase, stimulating the growth and development of the uterine lining. Estrogen also supports the maturation of ovarian follicles, which results in ovulation. In perimenopause and menopause, estrogen levels start to decline as the ovaries produce fewer hormones. This decline can result in irregular menstrual cycles, menopausal symptoms, and long-term effects such as bone loss and increased cardiovascular risk.
- Progesterone: After ovulation, progesterone levels rise during the second half of the cycle (luteal phase). Progesterone prepares the uterus for potential pregnancy, maintaining the thickened uterine lining and supporting implantation. If pregnancy does not occur, progesterone levels decrease, triggering menstruation. During perimenopause and menopause, progesterone production declines, leading to hormonal imbalances and irregular menstrual bleeding. This imbalance can contribute to symptoms such as mood changes, sleep disturbances, and changes in uterine bleeding patterns.
- Follicle-Stimulating Hormone (FSH): FSH is responsible for stimulating the growth and development of ovarian follicles. At the start of the menstrual cycle, FSH levels rise, signalling the ovaries to produce mature eggs. In perimenopause and menopause, as the number of ovarian follicles decreases, the feedback loop between the ovaries and the brain becomes disrupted. This leads to increased FSH levels as the body attempts to stimulate the ovaries to release eggs, resulting in irregular menstrual cycles and other menopausal symptoms.
- Luteinizing Hormone (LH): LH works in conjunction with FSH to regulate the menstrual cycle. Around the time of ovulation, LH levels surge, triggering the release of the mature egg from the ovary. In perimenopause and menopause, the overall levels of LH can become more erratic, leading to unpredictable ovulation patterns, and disrupted menstrual cycles.
Hormonal Imbalances: PCOS, Premenstrual Syndrome and Postpartum Depression
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women. One of the key features of PCOS is insulin resistance, which occurs when the body’s cells become less responsive to insulin, leading to an increase in circulating insulin levels. The pathophysiology of insulin resistance in PCOS is complex and not fully understood.
Women with PCOS often experience symptoms such as acne, hirsutism (unwanted hair growth), irregular menstrual cycles and anovulation. Women with PCOS often have higher circulating androgen levels. This is thought to be a result of the inverse relationship between Sex Hormone Binding Globulin (SHBG) and insulin. SHBG does what its name suggests, it binds our sex hormones. It is a metabolically active protein that binds estrogens, progesterone, and testosterone. Individuals with PCOS have higher insulin levels which in turn reduces SHBG. This results in an increase free testosterone level which is thought to be responsible for the hyperandrogenic symptoms in PCOS.
Progesterone plays a significant role in Premenstrual Syndrome (PMS), a collection of physical and emotional symptoms that occur in the days or weeks leading up to menstruation. During the menstrual cycle, progesterone levels rise after ovulation and decline before the next menstrual period starts. The fluctuation in progesterone levels is believed to contribute to the development of PMS symptoms.
Progesterone affects various neurotransmitters in the brain, including serotonin, which regulates mood. Low levels of serotonin have been associated with PMS symptoms such as irritability, mood swings, and depression. Progesterone interacts with serotonin receptors, influencing its production, release, and uptake. Imbalances in progesterone levels during the luteal phase of the menstrual cycle (the phase after ovulation) can potentially disrupt serotonin function, contributing to PMS symptoms (4,5).
In addition to serotonin, progesterone also affects the GABA (gamma-aminobutyric acid) system, which helps regulate anxiety and promotes feelings of calm and relaxation. Progesterone enhances GABA activity, leading to its calming effects. Fluctuations in progesterone levels can disrupt the balance of GABA, potentially contributing to anxiety and mood symptoms experienced in PMS (4,5).
The relationship between progesterone and PMS is complex, and individual variations in hormone sensitivity and metabolism can influence the severity and manifestation of symptoms. Some women may be more sensitive to progesterone fluctuations, leading to more pronounced PMS symptoms, while others may experience minimal or no symptoms at all.
It is worth noting that PMS is a common condition that affects many women to varying degrees. Lifestyle modifications like regular exercise, stress management techniques, and a balanced diet can help alleviate PMS symptoms. For some women with severe symptoms, hormonal treatments may be prescribed to help regulate hormonal fluctuations and reduce symptom severity.
The role of progesterone in postpartum depression (PPD) is an area of ongoing research and investigation. Progesterone, a hormone primarily produced during pregnancy, plays a vital role in maintaining pregnancy and preparing the body for childbirth. However, its role in the development of postpartum depression is complex and not fully understood.
During pregnancy, progesterone levels rise significantly, due in part to the production by the placenta. Progesterone levels peak in the third trimester. After childbirth and with the delivery of the placenta, progesterone levels drop rapidly, returning to pre-pregnancy levels within a few days. This dramatic decline in progesterone levels, coupled with other hormonal fluctuations and physiological changes, is believed to contribute to the development of postpartum depression.
Research suggests that progesterone may have mood-stabilizing and antidepressant effects. It is thought to interact with neurotransmitters, such as serotonin and GABA, which play crucial roles in mood regulation. Progesterone can also modulate the stress response system, influencing the body’s ability to cope with stress and adversity.
Several studies have explored the use of progesterone supplementation as a potential treatment for postpartum depression. Some preliminary findings suggest that progesterone therapy, particularly in women with low levels of the hormone after childbirth, may alleviate depressive symptoms (6,7).