A current perspective into young female sex hormone replacement: a review

ABSTRACT

Introduction

Hormone replacement in females with hypogonadism is advocated to address the various clinical aspects of estrogen deficiency.

Areas covered

This article focuses on hormone replacement in young females with hypogonadism, including a rationale as to why hormone replacement in such patients differs from treatment in postmenopausal females, a summary of symptoms encountered by females with hypogonadism and a comprehensive discussion of the various treatment options available, specifically focusing on the latest advances in the subject. A Medline search was conducted using different combinations of relevant keywords, giving preference to recent publications.

Expert opinion

Whilst traditionally oral contraceptive pills (containing ethynyl estradiol) were commonly used as a form of hormone replacement, it is now increasingly recognized that this is not the optimal treatment option. Physiological hormone replacement with transdermal estradiol is found to be superior. Evidence suggests that micronized progesterone may be associated with fewer side effects, although its effect on endometrial protection is not yet proven. Synthetic progestins confer varying degrees of androgenic and thromboembolic properties which should be kept in mind when prescribing individualized treatment. Further studies in different sub-cohorts of female patients with hypogonadism might help address the specific needs of individual patients.

KEYWORDS:

• Hormone replacement
• female hypogonadism
• premature ovarian insufficiency
• estrogen
• progestogen

Article highlights

• The etiology of female hypogonadism is varied and may be classified as premature ovarian insufficiency (failure arising from the ovaries themselves) or secondary gonadal failure, also known as hypogonadotropic hypogonadism; the result of inadequate gonadotropin stimulation.

• Women exhibiting features of gonadal failure prior to 50 years of age, especially prior to the age of 40, should be considered for sex hormone replacement therapy in order to avoid the complications of early menopause (menopausal symptoms, increased mortality mainly related to cardiovascular disease, bone health, and neurological sequelae).

• By prescribing sex hormone replacement, one aims to restore normal physiological states, therefore in such a context the term ‘replacement’ is indeed pertinent as opposed to the concept of ‘extension’ of hormone therapy in the post-menopausal age group.

• Hormonal replacement consists of an estrogen component as well as a progestogen component, in females possessing a uterus.

• Oestradiol is superior to ethinyloestradiol in terms of cardiovascular parameters, thromboembolic risk, and bone health. Furthermore, the use of transdermal or transvaginal estrogen therapy has been associated with a decreased risk of thromboembolism and possibly stroke, when compared to the classical oral formulation.

• Different progestogens have a varying affinity to the progesterone receptor and other steroid receptors: mineralocorticoid, glucocorticoid, and androgen receptors. These differing actions, together with other factors including route of administration, pharmacokinetics, and protein-binding strength, explains the differing androgenic and thromboembolic profiles.

• Treatment with testosterone was found to have positive effects on cardiometabolic risk factors, quality of life, and neurocognitive functions but long-term studies confirming safety and efficacy are lacking.

• With regards to follow up, a multidisciplinary setting is advisable and aims to address specific patients’ needs according to the varied aetiology of female hypogonadism.

Acknowledgments

The authors would like to thank Dr. Lianne Camilleri for her assistance in manuscript editing.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.