Estrogens, progestogens, androgens, mineralocorticoids, and glucocorticoids are the five primary human steroid hormones. The two most commonly used hormones during menopause are estrogens and progestogens. They come in a wide range of FDA-approved and non-FDA-approved preparations.
Long-term unopposed oestrogen therapy is associated with a significantly higher risk of endometrial hyperplasia (As there are too many cells in the uterus, the lining of the uterus (endometrium) becomes extremely thick) and endometrial cancer in women with intact uteruses, hence estrogens are nearly always given in combination with progestogens in women with intact uteruses. A progestogen is not necessary for women who have had a hysterectomy or do not have a uterus, and oestrogen can be taken alone. There are a variety of combination oestrogen and progestogen formulations available.
Hormone replacement can take a variety of forms, including:
- Bioidentical estrogens such as estradiol and estriol, animal-derived estrogens such as conjugated estrogens (CEEs), and synthetic estrogens such as ethinylestradiol are all examples of estrogens.
- Bioidentical progesterone and progestins (synthetic progestogens) such as medroxyprogesterone acetate (MPA), norethisterone, and dydrogesterone are examples of progestogens.
- Bioidentical testosterone and dehydroepiandrosterone (DHEA), as well as manufactured anabolic steroids such as methyltestosterone and nandrolone decanoate, are examples of androgens.
- Vaginal oestrogen can help with localised atrophy and dryness while having less systemic side effects than oestrogen administered through other routes. To manage a lack of libido, an androgen, usually testosterone, can be added.
Continuous versus cyclic
To more precisely replicate the ovarian hormone cycle, the dosage is frequently altered cyclically, with estrogens taken daily and progestogens administered for around two weeks every month or every other month, a regimen known as ‘cyclic’ or sequentially coupled.’ ‘Continuous combined’ HRT, on the other hand, can be given with a consistent daily hormonal dosage. Compared to cyclic HRT, continuous combined HRT is associated with less complicated endometrial hyperplasia. Both schedule timings appear to have a similar influence on breast density.
Route of administration
The drugs used in menopausal HRT come in a range of formulations and can be administered through a variety of routes:
- Tablets and capsules are used for oral administration.
- Patches, gels, and lotions are all examples of transdermal administration.
- Tablets, creams, suppositories, and rings are all used for vaginal administration.
- Intramuscular or subcutaneous injection – vials or ampoules of solutions.
- Subcutaneous implants are pellets that are surgically implanted into fat tissue.
- Sublingual, buccal, intranasal, and rectal administration are less prevalent, as are intrauterine devices.
More newly developed medication delivery methods are said to offer increased local effects, reduced dose, fewer side effects, and stable blood hormone levels rather than cyclical levels. Transdermal and vaginal estrogens, in particular, evade the liver’s first-pass metabolism. This, in turn, reduces the formation of anti-estrogenic metabolites and increases clotting factors, resulting in fewer negative side effects, particularly in terms of cardiovascular disease and stroke.
Due to the availability of alternate formulations, injectable versions of estradiol are no longer indicated in menopausal hormone therapy.
Bioidentical hormone therapy
The use of hormones that are chemically similar to those produced by the body is known as bioidentical hormone therapy (BHT). The Food and Drug Administration does not accept the phrase ‘bioidentical hormone,’ arguing that there is no scientific evidence that these hormones are identical to their naturally occurring counterparts. There are, however, FDA-approved products that contain ‘bioidentical’ hormones.
Bioidentical hormones can be found in pharmaceutical and compounded formulations, with the latter being discouraged by regulatory agencies due to a lack of standardisation and control. Most bioidentical hormone classifications ignore the goods’ production, source, or administration method, referring to both non-FDA-approved compounded products and FDA-approved medications as “bioidentical.”
The British Menopause Society has issued a consensus statement endorsing the distinction between “compounded” forms (cBHRT), which are unregulated, custom-made by speciality pharmacies, and heavily marketed, and “regulated” pharmaceutical grade forms (rBHRT), which are subject to formal oversight by entities such as the FDA and form the basis of most clinical trials. Some practitioners who prescribe compounded bioidentical HRT additionally use salivary or serum hormonal testing to track treatment response, which is not recommended by current clinical recommendations in the United States or Europe.
Bioidentical hormones in pharmaceuticals may have inadequate therapeutic data, as there have been no randomised controlled prospective trials comparing them to animal-derived analogues yet. Preclinical evidence points to a lower risk of venous thromboembolism, cardiovascular disease, and breast cancer. The North American Menopause Society, the Endocrine Society, the International Menopause Society, and the European Menopause and Andropause Society all recommended bioidentical medicines for people with a higher clotting risk as of 2012.