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Long-term effects of cyclic combined conjugated estrogens and dydrogesterone in post-menopausal women
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
M. Gambacciani, M. Ciaponi, B. Cappagli, L. Piaggesi, C. Benussi, S. Picchetti, A. R. Genazzani
Hormonal replacement therapy is currently used for the control of climacteric symptoms, and for the prevention of long-term consequences of menopause. Chronic hypoestrogenism in post-menopausal years causes a critical decrease in bone mineral density (BMD) that is an important determinant of fracture risk1-5. Estrogen replacement therapy prevents the lowering of BMD related to peri-and post-menopausal hypoestrogenism4-7. In addition, post-menopausal estrogen supplementation can exert cardioprotective effects with substantial reduction of morbidity and mortality for cardiovascular disease8-16. During estrogen therapy, progestin supplementation is mandatory to prevent endometrial hyperstimulation17-23 . However, the administration of progestogens can jeopardize the beneficial effects of estrogens on cardiovascular protection24, 25. The metabolic effects depend on the type and dose of progestogens. Dydrogesterone (DD) is a potent orally active progestogen, similar to endogenous progesterone in its molecular structure and biological actions, and devoid of any androgenic, anabolic or estrogenic effect26-31. Sequential DD administration was reported to antagonize the estrogenic effect on endometrial profferation26-31. In the present paper we report clinical and metabolic effects of the long-term administration of DD in combination with conjugated estrogens (CE) in early post-menopausal women.
Debate: Should Progestogens Be Used in Recurrent Pregnancy Loss? Yes
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
In addition to micronized progesterone, a stereoisomer of progesterone dydrogesterone has been widely studied in various clinical trials. Dydrogesterone has 5–6 times higher bioavailability than progesterone itself and higher receptor binding selectivity [8]. These result in a significantly lower oral therapeutic dose, which is approximately 10–20 times less than micronized progesterone. El-Zibdeh [9] conducted a three-arm study on 180 women that compared dydrogesterone treatment with human chorionic gonadotropin (hCG), both in combination with standard supportive care and with standard supportive care alone. Women recruited for the study were less than 35 years old with history of ³3 unexplained recurrent consecutive miscarriages. All women received standard supportive care, including multivitamin supplements and recommended bed rest, and were followed routinely in the antenatal clinic. Eighty-two women received dydrogesterone 10 mg twice daily with standard supportive care from diagnosis of pregnancy until 12 weeks, 50 women received hCG 5000 IU intramuscularly every 4 days with standard supportive care from diagnosis of pregnancy until 12 weeks, and in the third arm 48 women (controls) received standard supportive care alone. Miscarriage was significantly (p ≤ 0.05) more common in the control group (29%; 14/48 women) than in the dydrogesterone group (13.4%; 11/82 women). There were no significant differences between the hCG group (18%; 9/50 women) and the control group [9].
Management
Published in John C Stevenson, Michael S Marsh, An Atlas of Osteoporosis, 2007
John C Stevenson, Michael S Marsh
Whilst a dose-dependent effect of estrogen has been shown in several studies, it has also been found that older postmenopausal women may not need as much estrogen as younger women to achieve the same skeletal effect. Lees and Stevenson9 conducted a double-blind, randomized, placebocontrolled study of the effects of two different doses (1 mg and 2 mg) of oral estradiol with the cyclical addition of various doses of dydrogesterone. Spinal and hip bone density was measured by dual-energy X-ray absorptiometry (DEXA) for 2 years. The bone density rose in all treated groups, with a somewhat greater increase with the higher dose, and fell in the placebo group. The increase in spine bone density for the 1-mg estradiol group in the oldest quartile of women was similar to that seen with 2 mg estradiol in the youngest quartile of women (Figure 6.1).
The expressions of matrix metalloproteinase-9, estrogen receptor, and progesterone receptor in thin endometrial tissue and their significance
Published in Gynecological Endocrinology, 2022
Lin-Hong Li, Gang Shi, Jin-Bing Pan, Cai-Hong Wang, Min Zhao, Xiu-Ping Zhang
Treatment method: at 3–5 days of menstruation in the second month after the cubital venous blood sampling, the patients began taking Progynova (estradiol valerate tablets), two tablets twice a day (1 mg per tablet). Patients with amenorrhea began hormone therapy after the cubital vein blood drawing. Endometrial thickness was measured using transvaginal ultrasound 3–5 days later. If the endometrial thickness was ≧7 mm, the Progynova dose was maintained, and if the endometrial thickness was <7 mm, the dose was increased. Additionally, Dydrogesterone tablets were taken at around 14 days of menstruation, two tablets twice a day (10 mg per tablet). After 10 days, both the Progynova and the Dydrogesterone tablet treatments were discontinued. The midluteal phase endometrial thickness was measured using vaginal ultrasound again; the treatment was discontinued if the endometrial thickness was ≧7 mm. If the endometrial thickness was still <7 mm after the first treatment cycle, a second treatment cycle was started. Progynova and Dydrogesterone tablets were discontinued in the last cycle, and oral proganolide was started after 5 days; the initial dose was then increased. Patients with an ultrasound-measured midluteal phase endometrial thickness of <7 mm were assigned to the thin endometrium group, and patients with an endometrial thickness ranging 7–10 mm were assigned to the normal endometrium group.
Reviewing the role of progesterone therapy in endometriosis
Published in Gynecological Endocrinology, 2019
Abdul Kadir Abdul Karim, Mohamad Nasir Shafiee, Nor Haslinda Abd Aziz, Mohd Hashim Omar, Nur Azurah Abdul Ghani, Pei Shan Lim, Reena Rahayu Md Zin, Norfilza Mokhtar
Dydrogesterone is a synthetic derivative of retroprogesterone, a stereoisomer of progesterone, with an additional double bond between carbon 6 and 7. Dydrogesterone is a highly selective progestin, which resembles progesterone mainly in its progestogenic effects and less in its andorgenic, anti-androgenic, glucocorticoid and anti-glucocorticoid effects. Due to its retrostructure, it binds almost exclusively to the PR. It has a strong agonistic activity for PR-B and only a weak agonistic activity for PR-A. This selectivity results in minimal or no unwanted side-effects [46,47].
Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman’s journey
Published in Gynecological Endocrinology, 2021
Luteal phase support increases the likelihood of a successful outcome with assisted reproduction techniques [36,37]. A Cochrane review found that micronized progesterone was associated with a lower clinical pregnancy rate than synthetic progesterone when used as luteal phase support (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.66–0.96; four studies), although there was no significant difference in the live birth rate (two studies) [36]. Dydrogesterone was the synthetic progesterone used in three of the four studies.