Today’s Subject: Hormone Replacement Therapy (HRT) – Part 2.

Part 2: Here we address the hormones involved in menopause and HRT.
There are three forms of oestrogen responsible for female reproduction, oestradiol, oestriol, and oestrone.
Oestradiol is the most predominant form of Oestrogen during the reproductive years in females, Oestriol is perhaps the most important in pregnant females and Oestrone is predominant during the female menopausal years and is a major player in menopausal women.
Oestradiol becomes active during puberty. It increases during ovulation and decreases during menstruation. Levels of Oestradiol slowly decrease with age, a notable reduction occurs during menopause.
A synthetic form of Oestradiol is used in Hormone Replacement Therapy (HRT) for menopausal women to help reduce the uncomfortable symptoms of menopause which occur as a result of reduced Oestradiol production. These symptoms include night sweats, hot flushes, vaginal dryness, fatigue and mood swings. However, because this is a synthetic drug there are many side effects and results tend to vary.
If too little Oestradiol is produced this can cause issues with bone development and bone density, leading to skeletal problems such as osteoporosis (Smith, Richardson, 1941).

Oestrone is often used as a reservoir for Oestradiol.
Testosterone is also very important due to the fact that it too can be converted from progesterone and into Oestradiol via aromatase and then into Oestrone.
It is not directly active in the tissue that Oestradiol is but is readily available for conversion into its fellow Oestrogen when required for actual use. Due to this Oestrone is often thought of as an Oestradiol precursor hormone, but the conversion can go both ways (Melmed et al 2011).
Oestrone is considered weaker than Oestradiol, and sometimes safer, but larger quantities are needed to get the equal effect as a smaller quantity of Oestradiol, making it rather dangerous in these instances.
If too much Oestrone is produced this can lead to Oestrogen-dependent cancers such as uterine, endometrial and breast cancers. Other symptoms of overproduction of Oestrone include, tenderness of the breast and pain, menorrhagia, metrorrhagia, other menstrual disorders, cervical secretions, hypertension, headache, nausea, cramping, visual impairment, endometrial pain if a woman is breastfeeding Oestrone can cause a decrease in the production of breast milk.
If Oestrone production is reduced it can also cause fatigue, anxiety, depression, hot flushes, decreased sex drive and Osteoporosis.
Oestrone is believed to cause cancer by facilitating cells proliferate. After the hormone binds to its receptors in a cell, it turns on hormone-responsive genes that promote DNA synthesis and cell proliferation. If a cell happens to have cancer-causing mutations, those cells will also proliferate and have a chance to grow into tumours or cancers. Oestrone is believed to be causative factor in endometrial, uterine and breast cancers. 80% of breast cancers rely on the supply of some form of Oestrogen to develop, these are known as hormone-receptor-positive cancers. (Picazo, Salcedo, 2003). Females who commence menstruation early in life and experience menopause later in life are at a higher risk of these cancers due to more production of Oestrogens, particularly Oestrone, over a lifetime.
Oestrone is the second major circulating Oestrogen in premenopausal woman, and the most important in post-menopausal women (Melmed et al 2011). Conversion rates of Oestrone from androstenedione steadily increases with age as well as with obesity due to its production in adipose tissue. It is higher in woman who have higher lower body obesity that those who have higher body obesity due to body fat distribution of the adipose.
Oestrone is responsible for breast tenderness, menstrual cramping, nausea and headaches experienced during premenstrual syndrome. The symptoms of menopause such as hot flushes, night sweats, irritability, headaches, body aches, memory loss, as well as anxiety and depression can be attributed to the increase of Oestrone which starts to surge during this period of a female’s life.
Research shows that Oestriol can reduce symptoms of menopause such as vaginal dryness and hot flushes (Tzingounis et al 1978) and is thought to be safer than others of the Oestrogen group.
If levels of Oestriol become too low however, this can have an effect on bone density, the cardiovascular system, urinary tract health and multiple sclerosis. (Tzingounis et al 1978).
During menopause a common complaint is vaginal dryness and Cystitis. The vagina and urinary tract lining becomes weak with age and start to degenerate, this can cause vaginal dryness, urinary tract infections and pain during intercourse. Oestriol aids in the strengthening and maintenance of the urinary tract, helping to reduce symptoms.

When it comes to the effects of synthetic hormone replacement therapy for menopausal females there are both arguments for and against this form of therapy. On one hand the risk of developing CAD, pulmonary embolism, and cancers is increased but the effect on symptom reduction can be of great benefit to those suffering from severe oestrogen withdrawal as a result of menopause can provide significant relief from discomfort. It is a decision which should not be approached lightly but at the end of the day it is an individual’s decision and as practitioners all we can do is give the evidence and let them make an informed choice.

Aly Curd


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