HRT for women with premature ovarian insufficiency: a comprehensive review

Abstract

BACKGROUND Premature ovarian insufficiency (POI), often and misleadingly referred to as ‘premature menopause’, is defined as a loss of ovarian activity before the age of 40 years and is characterized by irregular or absent periods and reduced fertility. Symptoms include those associated with the natural menopause (night sweats and vaginal dryness), and with the long-term adverse effects of estrogen deficiency (osteoporosis and cardiovascular disease): the latter is believed to explain the shorter life expectancy associated with POI. OBJECTIVE AND RATIONALE The objective of the current review was to collect all relevant studies supporting recommendations on the indications, treatment options, and risks of hormone replacement therapy (HRT) (estrogen, progestogens and androgens) for women with POI. SEARCH METHODS The current review was written based on the best available evidence on the topic collected for the recently published ESHRE guideline on the management of women with POI. PUBMED/MEDLINE and the Cochrane library were searched in a stepwise approach. Relevant references were summarized in evidence tables, with assessment of the quality. OUTCOMES HRT is strongly recommended for women with POI, mainly for vasomotor and genito-urinary symptom relief. In addition, HRT has been shown to have a role in bone protection and probably also in primary prevention of cardiovascular disease. There is little evidence on the optimal type, regimen and dose of HRT; patient preference for route and method of administration of each component of HRT must be considered when prescribing, as should contraceptive needs. In women with POI, physiological replacement of estrogen (and progesterone) is essential for their health, and the controversies that surround the use of HRT in postmenopausal women do not apply. LIMITATIONS, REASONS FOR CAUTION N/A. WIDER IMPLICATIONS New areas of study on HRT for women with POI should focus on life expectancy, quality of life and neurological function. Furthermore, randomized controlled trials comparing transdermal estradiol with oral estrogens with regard to efficacy, patient satisfaction and side effects are urgently needed. STUDY FUNDING/COMPETING INTERESTS The authors received no funding for the review. The costs for the development of the ESHRE guideline were covered by ESHRE. The authors have no conflicts of interest to disclose.

Premature ovarian insufficiency: A hormonal treatment approach

“…Subsequent tests should be carried out depending on these initial results (new evaluations are especially recommended in cases where there is already bone loss and/or osteoporosis), the use or not of hormone replacement therapy (HRT), and to evaluate therapeutic response in cases of osteoporosis. (1,9,19) • Pelvic Ultrasound: Might be indicated for the differential diagnosis of other causes of amenorrhea. (1) Treatment: What are the goals?…”

“…Although vasomotor symptoms (hot flushes) are the main apparent reason for the use of HRT, reasons related to greater morbidity (i.e., bone loss) must be made clear and reinforced to the patient. (19) Psychosocial support should be offered, with special care regarding the reproductive aspects. (1) Estrogen replacement is recommended to maintain bone health, prevent osteoporosis, and reduce the risk of fracture.…”

“…Among estrogen options, estradiol is the most physiological option in terms of cardiovascular effect when compared to combined hormonal contraceptives (CHCs). (19) Conjugated equine estrogen choices are not in the ESHRE consensus, however the American College of Obstetrics and Gynecology (ACOG) considers them a valid choice for HRT in women with POI. (19)(20)(21)(22) The most widely used progestagens for HRT in women with POI are medroxyprogesterone acetate (MPA), natural micronized progesterone and norethisterone.…”

“…In cyclic regimens progestagen is administered for 12 to 14 consecutive days/month in higher doses when compared to continuous use. (19) With the exception of the first years of pubertal development, no regimen has been proven more beneficial than the other; the patient must be asked whether they prefer to undergo periodic withdrawal bleeding or not. (19) A levonorgestrel-releasing intrauterine device/system is an alternative to oral progestagen, and given its contraceptive action it may also be attractive to women who do not wish to risk pregnancy, in cases where this might be an eventual risk.…”

“…(19) A levonorgestrel-releasing intrauterine device/system is an alternative to oral progestagen, and given its contraceptive action it may also be attractive to women who do not wish to risk pregnancy, in cases where this might be an eventual risk. (19)(20)(21)(22) Hysterectomized women will not require the association of progestogens duringestrogen replacement, with the exception of cases where there is previous endometriosis. (19) Transdermal estrogen (adhesive patches or gel) avoids hepatic first-pass and is associated, when compared to oral estrogen, to a lower risk of venous thromboembolism (VTE), in addition to showing serum hormonal levels closer to age-related physiological levels.…”