Hormone Replacement Therapy: Medical Uses

Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT) or postmenopausal hormone therapy (PHT, PMHT), is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal atrophy, accelerated skin aging, vaginal dryness, decreased muscle mass, sexual dysfunction, and bone loss. The current indications for use from the United States Food and Drug Administration (FDA) include short-term treatment of menopausal symptoms, such as vasomotor hot flashes or vaginal atrophy, and prevention of osteoporosis. Having HRT a serious problem and multiple medical uses, Siddha Spirituality of Swami Hardas Life System appeals to all our readers to know in-depth about it for well-being.

Medical uses of Hormone replacement therapy

Approved uses of HRT in the United States include short-term treatment of menopausal symptoms such as hot flashes and vaginal atrophy and prevention of osteoporosis. The American College of Obstetrics and Gynecology (ACOG) approves of HRT for symptomatic relief of menopausal symptoms and advocates its use beyond the age of 65 inappropriate scenarios. The North American Menopause Society (NAMS) 2016 annual meeting mentioned that HRT may have more benefits than risks in women before the age of 60.

The Women’s Health Initiative (WHI) was a study of over 27,000 women beginning in 1991. Successive analyses have found sometimes contradictory results, with the most recent publication in 2017 finding no difference for all-cause mortality with HRT. The effects of HRT on most organ systems vary by age and time since the last physiological exposure to hormones, and there can be differences in individual regimens, factors which have made analyzing effects difficult. Demographically, the vast majority of data available is in postmenopausal American women with concurrent pre-existing conditions, and with a mean age of over 60 years.

Menopausal symptoms

HRT is often given as a short-term relief from menopausal symptoms during perimenopause. Potential menopausal symptoms include:

• Hot flashes – vasomotor symptoms
• Vulvovaginal atrophy – atrophic vaginitis and dryness
• Dyspareunia – painful sexual intercourse due to vaginal atrophy and lack of lubrication
• Bone loss – decreased bone mineral density, which can eventually lead to osteopenia, osteoporosis, and associated fractures
• Decreased sexual desire
• Defeminization – diminished feminine fat distribution and accelerated skin aging
• Sleep disturbances and joint pain

The most common of these are loss of sexual drive and vaginal dryness.

Heart disease

The effect of HRT in menopause appears to be divergent, with lower risk when started within five years. There may be an increase in heart disease if HRT is given twenty years post-menopause. There is, however, no actual difference in long-term mortality from HRT, regardless of age.

A Cochrane review suggested that women starting HRT less than 10 years after menopause had lower mortality and coronary heart disease, without any strong effect on the risk of stroke and pulmonary embolism. Those starting therapy more than 10 years after menopause showed little effect on mortality and coronary heart disease, but an increased risk of stroke. Both therapies had an association with venous clots and pulmonary embolism.

HRT also improves cholesterol levels. With menopause, HDL decreases, while LDL, triglycerides, and lipoprotein increase, patterns that reverse with estrogen. Beyond this, HRT improves heart contraction, coronary blood flow, sugar metabolism, and decreases platelet aggregation and plaque formation. HRT may promote reverse cholesterol transport through the induction of cholesterol ABC transporters.

Blood clots

Effects of hormone replacement therapy on venous blood clot formation and potential for pulmonary embolism may vary with different estrogen and progestogen therapies, and with different doses or methods of use. Comparisons between routes of administration suggest that when estrogens are applied to the skin or vagina, there is a lower risk of blood clots, whereas when used orally, the risk of blood clots and pulmonary embolism is increased.

Skin and vaginal routes of hormone therapy are not subject to the first-pass metabolism, and so lack the anabolic effects that oral therapy has on the liver synthesis of vitamin K-dependent clotting factors, possibly explaining why oral therapy may increase blood clot formation.

While a 2018 review found that taking progesterone and estrogen together can decrease this risk, other reviews reported an increased risk of blood clots and pulmonary embolism when estrogen and progestogen were combined, particularly when treatment was started 10 years or more after menopause and when the women were older than 60 years.

Stroke

Multiple studies suggest that the possibility of HRT related stroke is absent if therapy is started within five years of menopause and that the association is absent or even preventive when given by non-oral routes. Ischemic stroke risk was increased during the time of intervention in the WHI, with no significant effect after the cessation of therapy and no difference in mortality at long term follow up.

When oral synthetic estrogen or combined estrogen-progestogen treatment is delayed until 5 years from menopause, cohort studies in Swedish women have suggested an association with hemorrhagic and ischemic stroke. Another large cohort of Danish women suggested that the specific route of administration was important, finding that although oral estrogen increased the risk of stroke, absorption through the skin had no impact, and vaginal estrogen actually had a decreased risk.

Breast cancer

Studies regarding the association of breast cancer with hormone replacement have been mixed and vary with the type of replacement used.

There is a non-statistically significant increased rate of breast cancer for hormone replacement therapy with synthetic progesterone. The risk may be reduced with bioidentical progesterone, though the only prospective study that suggested this was underpowered due to the rarity of breast cancer in the control population. 

The WHI also found a non-significant trend in the estrogen-alone clinical trial towards a reduced risk of breast cancer, though estrogen is usually only given alone in the setting of a hysterectomy due to the effect of unopposed estrogen on the uterus.

For women who previously have had breast cancer, it is recommended to first consider other options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators (SERMs) for osteoporosis, cholesterol-lowering agents, and aspirin for cardiovascular disease, and vaginal estrogen for local symptoms. Observational studies of systemic HRT after breast cancer are generally reassuring. If HRT is necessary after breast cancer, estrogen-only therapy, or estrogen therapy with progestogen may be safer options than combined systemic therapy.

Colorectal cancer

In the WHI, women who took combined estrogen-progesterone therapy had a lower risk of getting colorectal cancer. However, the cancers they did have were more likely to have spread to lymph nodes or distant sites than colorectal cancer in women not taking hormones.

Ovarian cancer

A 2015 meta-analysis found that HRT was associated with an increased risk of ovarian cancer, with women using HRT having about one additional case of ovarian cancer per 1,000 users. This risk is decreased when progestogen therapy is given concomitantly, as opposed to estrogen alone, and also decreases with increasing time since stopping HRT. Regarding the specific subtype, there may be a higher risk of serious cancer, but no association with clear cell, endometrioid, or mucinous ovarian cancer.

Sexual function

HRT can help with the lack of sexual desire and sexual dysfunction that can occur with menopause. Epidemiological surveys of women between 40–69 years suggest that 75% of women remain sexually active after menopause. With increasing life spans, women today are living one third or more of their lives in a postmenopausal state, a period during which healthy sexuality can be integral to their quality of life.

Decreased libido

A major complaint among postmenopausal women has decreased libido. Several hormonal changes take place during this period, including a decrease in estrogen and an increase in the follicle-stimulating hormone.

Testosterone

For most women, the majority of change occurs during the late perimenopausal and postmenopausal stages. A decrease in sex hormone-binding globulin (SHBG) and inhibin (A and B) also occurs. Testosterone, a hormone more commonly associated with males, is also present in women at a lower level. It peaks at age 30 but declines gradually with age. There is little variation across the lifetime and during the menopausal transition. With surgical menopause, testosterone declines more sharply and can result in more severe symptoms. HRT can help with sexual difficulties related to pain and lubrication.

Preexisting sexual difficulties

Not all women are responsive, especially those with preexisting sexual difficulties. Estrogen replacement can restore vaginal cells, pH levels, and blood flow to the vagina, all of which tend to deteriorate at the onset of menopause. Pain or discomfort with sex appears to be the most responsive component to estrogen. It also has been shown to have positive effects on the urinary tract. Reduced vaginal atrophy and increased sexual arousal, frequency, and orgasm have also been noted.

Estrogen/androgen replacement therapy

The effectiveness of hormone replacement can decline in some women after long-term use. A number of studies have also found that the combined effects of estrogen/androgen replacement therapy can increase libido and arousal over estrogen alone.

A new form of HRT

Findings on a relatively new form of HRT called tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, suggest that it has the ability to improve mood, libido, and physical symptoms of surgically menopausal women to a greater degree than ERT.

Vasomotor symptoms

In various placebo-controlled studies, improvements in vasomotor symptoms, emotional response, sleep disturbances, physical symptoms, and sexual desire have been observed. Tibolone has been used in Europe for almost two decades but is not available in North America at this point.

Neurodegenerative disorders

HRT may increase the risk of dementia if initiated after 65 years of age, but have a neutral outcome or be neuroprotective for those between 50–55 years. HRT can also improve executive and attention processes outside of the context of dementia in postmenopausal women.

Muscle 

Hormone replacement therapy in the form of estrogen and androgen. It can be effective at reversing the effects of aging on muscle.

Side effects of Hormone replacement therapy

Some common and uncommon side effects include:

Contraindications of Hormone replacement therapy

The following are absolute and relative contraindications to HRT:

Absolute contraindications of Hormone replacement therapy

• Undiagnosed vaginal bleeding
• Severe liver disease
• Pregnancy
• Severe coronary artery disease
• Aggressive breast, uterine or ovarian cancer

Relative contraindications of Hormone replacement therapy

• Migraine headaches
• History of breast cancer
• History of ovarian cancer
• Venous thrombosis
• History of uterine fibroids
• Atypical ductal hyperplasia of the breast
• Active gallbladder disease (cholangitis, cholecystitis)
• Well-differentiated and early endometrial cancer – once treatment for the malignancy is complete, is no longer an absolute contraindication.

Reference: https://en.wikipedia.org/wiki/Hormone_replacement_therapy