Bleeding patterns during continuous estradiol with different sequential progestogens therapy

Carlo, Costantino Di; Sammartino, A; Sardo, Attilio Di Spiezio; Tommaselli, Giovanni A.; Guida, Maurizio; Mandato, Vincenzo Dario; D’Elia, A; Nappi, Carmine

doi:10.1097/01.gme.0000178450.29377.c9

Cited by 19 publications

(21 citation statements)

References 33 publications

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“…In those studies with head-tohead comparisons, there were no significant group differences for endometrial thickness at baseline and after 12 cycles 5,6 . When comparing the baseline endometrial thickness with that at study closure, there was either no change (extended cycle regimen at oral MP 100 mg/day 21 , sequential regimen at vaginal MP 200 mg/day 5 ), or a significant increase 5,6 . Another two small, non-controlled studies using either oral MP 200-300 mg/day for 10 days per month 16 or 100 mg/day for 23 days per month 10 reported no change 10 or an endometrial thickness of less than 2 mm after 1 year 16 .…”

Section: Endometrial Thicknessmentioning

confidence: 86%

“…Participants received continuous, transdermal estradiol (E2) (25 21 -50 5,6 lg/ day) which was sequentially combined with either different oral progestogens (medroxyprogesterone acetate (MPA), nomegestrol acetate (NOMAC), dydrogesterone (DYD), MP) 6 , MP applied orally or vaginally at different dosages (100 or 200 mg/day) 5 or oral MP 100 mg/day for 2 weeks every 6 months (extended cycle) 21 . In those studies with head-tohead comparisons, there were no significant group differences for endometrial thickness at baseline and after 12 cycles 5,6 . When comparing the baseline endometrial thickness with that at study closure, there was either no change (extended cycle regimen at oral MP 100 mg/day 21 , sequential regimen at vaginal MP 200 mg/day 5 ), or a significant increase 5,6 .…”

Section: Endometrial Thicknessmentioning

confidence: 99%

“…Endometrial thickness measured by TVUS was assessed in postmenopausal women in one 3-year, placebo-controlled, randomized, controlled trial (RCT) (n ¼ 167) 21 and two 1-year RCTs (n ¼ 100) with head-to-head comparisons 5,6 . Participants received continuous, transdermal estradiol (E2) (25 21 -50 5,6 lg/ day) which was sequentially combined with either different oral progestogens (medroxyprogesterone acetate (MPA), nomegestrol acetate (NOMAC), dydrogesterone (DYD), MP) 6 , MP applied orally or vaginally at different dosages (100 or 200 mg/day) 5 or oral MP 100 mg/day for 2 weeks every 6 months (extended cycle) 21 .…”

Section: Endometrial Thicknessmentioning

confidence: 99%

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The impact of micronized progesterone on the endometrium: a systematic review

2016

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Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. International guidelines on menopausal hormone therapy (MHT) do not specify on progestogen type, dosage, route of application and duration of safe use. At the same time, the debate on bioidentical hormones including micronized progesterone increases. Based on a systematic literature review on micronized progesterone for endometrial protection, an international expert panel's recommendations on MHT containing micronized progesterone are as follows: (1) oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years; (2) vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use); (3) transdermal micronized progesterone does not provide endometrial protection.

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Section: Endometrial Thicknessmentioning

confidence: 86%

Section: Endometrial Thicknessmentioning

confidence: 99%

Section: Endometrial Thicknessmentioning

confidence: 99%

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The impact of micronized progesterone on the endometrium: a systematic review

2016

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“…[5][6][7] More than half of users of this regimen may bleed before day 11 of the progestogen sequence and less than 10% of women may experience recurrent episodes of breakthrough bleeding. 8 On the other hand, the percentage of women with abnormal bleeding on the combined continuous regimen, either oral or transdermal, ranges from, 0% to 77% in the first few years of treatment.…”

Section: Causes Of Unscheduled Bleeding On Hrtmentioning

confidence: 99%

“…8 On the other hand, the percentage of women with abnormal bleeding on the combined continuous regimen, either oral or transdermal, ranges from, 0% to 77% in the first few years of treatment. 7,9,10 With the continuous regimen, the percentage of women with bleeding decreases after 6 to 12 months of use and after 9 months, it is expected that only 3% to 10% will still present this complication. 11 In the transdermal route, the percentage of women who still present bleeding or spotting after 12 months of use ranges from 10% to 20%.…”

Section: Causes Of Unscheduled Bleeding On Hrtmentioning

confidence: 99%

Unscheduled bleeding on HRT - do we always need to investigate for endometrial pathology?

Lou

Kannappar

Sathiyathasan

2017

Int J Reprod Contracept Obstet Gynecol

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Hormone replacement therapy (HRT) is the most effective method for relieving the effects of hypoestrogenism following menopause. Despite the benefit of the HRT, unscheduled/breakthrough bleeding decreases patients’ compliance with long-term use. The underlying mechanisms for this unpredictable breakthrough bleeding are less well understood. In the event of unscheduled bleeding, investigation may be necessary according to local protocol. Whilst the incidence of underlying benign pathology may be quite high, the likelihood of malignancy is low and unless there is particular clinical concern, these women do not need fast track referral which should be reserved for women with true postmenopausal bleeding.

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Diagnostic and therapeutic use of oral micronized progesterone in endocrinology

Memi,

Pavli,

Papagianni

et al. 2024

Rev Endocr Metab Disord

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Progesterone is a natural steroid hormone, while progestins are synthetic molecules. In the female reproductive system, progesterone contributes to the control of luteinizing hormone and follicle-stimulating hormone secretion and their pulsatility, via its receptors on the kisspeptin, neurokinin B, and dynorphin neurons in the hypothalamus. Progesterone together with estradiol controls the cyclic changes of proliferation and decidualization of the endometrium; exerts anti-mitogenic actions on endometrial epithelial cells; regulates normal menstrual bleeding; contributes to fertilization and pregnancy maintenance; participates in the onset of labor. In addition, it exerts numerous effects on other endocrine systems. Micronized progesterone (MP) is natural progesterone with increased bioavailability, due to its pharmacotechnical micronized structure, which makes it an attractive diagnostic and therapeutic tool. This critical literature review aims to summarize and put forward the potential diagnostic and therapeutic uses of MP in the field of endocrinology. During reproductive life, MP is used for diagnostic purposes in the evaluation of primary or secondary amenorrhea as a challenge test. Moreover, it can be prescribed to women presenting with amenorrhea or oligomenorrhea for induction of withdrawal bleeding, in order to time blood-sampling for diagnostic purposes in early follicular phase. Therapeutically, MP, alone or combined with estrogens, is a useful tool in various endocrine disorders including primary amenorrhea, abnormal uterine bleeding due to disordered ovulation, luteal phase deficiency, premenstrual syndrome, polycystic ovary syndrome, secondary amenorrhea [functional hypothalamic amenorrhea, premature ovarian insufficiency], perimenopause and menopause. When administrated per os, acting as a neurosteroid directly or through its metabolites, it exerts beneficial effects on brain function such as alleviation of symptoms of anxiety and depression, asw well as of sleep problems, while it improves working memory in peri- and menopausal women. Micronized progesterone preserves full potential of progesterone activity, without presenting many of the side-effects of progestins. Although it has been associated with more frequent drowsiness and dizziness, it can be well tolerated with nocturnal administration. Because of its better safety profile, especially with regard to metabolic ailments, breast cancer risk and veno-thromboembolism risk, MP is the preferred option for individuals with an increased risk of cardiovascular and metabolic diseases and of all-cause mortality.

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Bleeding patterns during continuous estradiol with different sequential progestogens therapy

Abstract: : Our data suggest that CS-EPT generally leads to regular withdrawal bleeding in women without uterine pathology. Micronized progesterone seems to induce more irregular bleeding episodes.

Cited by 19 publications

References 33 publications

The impact of micronized progesterone on the endometrium: a systematic review

The impact of micronized progesterone on the endometrium: a systematic review

Unscheduled bleeding on HRT - do we always need to investigate for endometrial pathology?

Diagnostic and therapeutic use of oral micronized progesterone in endocrinology

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