Long-term effects of progestins on bone quality and fractures

Thijssen, J. H. H.

doi:10.1080/09513590701584931

Cited by 6 publications

(6 citation statements)

References 70 publications

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“…The benefits include, reduction of heavy menstrual bleeding due to the high incidence of amenorrhea after longer use, a reduced risk of pelvic inflammatory disease, reduction of endometriotic pain, fewer painful crisis in women with sickle cell disease and reduction in vasomotor symptoms [ 20 ].…”

Section: Health Risks and Benefitsmentioning

confidence: 99%

The clinical relevance of progestogens in hormonal contraception: Present status and future developments

Regidor¹

2018

Oncotarget

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The contraceptive pill is an effective and very safe method to control pregnancies. It was developed 60 years ago, and despite, that the composition has been the same since it was first developed (estrogen and progestogen), along the years the concentration of ethinyl estradiol has been reduced to improve tolerability. Nevertheless, progestogens are the basic active agent of hormonal contraception. The mechanism of progestogens is a multimodal one and basically three modes of contraceptive action can be distinguished:(a) A strong antigonadotrophic action leading to the inhibition of ovulation. The necessary dosage of ovulation inhibition per day is a fixed dosage that is inherent to each progestogen and independent of the dosage of estrogen used or the partial activities of the progestogen or the mode of application. (b) Thickening of the cervical mucus to inhibit sperm penetration and (c) Desynchronization of the endometrial changes necessary for implantation.The on the market available progestogens used for contraception are either used in combined hormonal contraceptives (in tablets, patches, or vaginal rings) or as progestogen only contraceptives. Progestogen only contraceptives are available as daily oral preparations, monthly injections, implants (2-3 years), and Intrauterine Systems (IUS). Even the long acting progestogens are highly effective in typical use and have a very low risk profile, with few contraindications.According to their introduction into the market progestogens, in combined hormonal contraceptives, have been described as first, second, third and fourth generation progestogens. Also, progestogens can be derived from testosterone, progesterone, and spironolactone that determine pharmacodynamic and pharmacokinetic differential effects. These effects contribute to the tolerability and additional beneficial or therapeutic effects whether used in combined oral contraceptives COC or as progestogen only drugs enhancing the individual options for different patient profiles.The new development of polymers for vaginal rings allowed on one side the improvement of the estrogen/progestogen combination in these rings especially regarding the comfort of use for women (avoiding of cold chain use or packages with up to six-month rings e.g.) and on the other side the development of progestogen only formulations. Another future development will be the introduction of new progestogen only pills that will provide effective contraceptive protection with more favourable bleeding patterns and a maintenance of ovulation inhibition after scheduled 24-h delays in pill intake than the existing pop with desogestrel.

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Section: Health Risks and Benefitsmentioning

confidence: 99%

The clinical relevance of progestogens in hormonal contraception: Present status and future developments

Regidor¹

2018

Oncotarget

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“…In 2007, Thijssen [44] concluded in a review that among adolescents (menarche to 518 years), the advantages of using progestin-only contraceptives outweigh the theoretical safety concerns regarding fracture risk. The WHO statement concludes that there should be no restriction on the use of progestin-only contraceptive methods among women who are otherwise eligible to use these methods.…”

Section: Progestin-only Oral Contraceptivesmentioning

confidence: 99%

Bone health in estrogen-free contraception

Hadji

Colli

Regidor³

2019

Osteoporos Int

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Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.

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“…36 Although a few early clinical studies suggested that there may be some beneficial effects of progesterone and progestins on bone, 37 more recent clinical trials do not provide evidence that progesterone or ''pure'' (PR-selective) progestins improve bone density in postmenopausal, hysterectormized, or amenorrheic women. 38 The role of androgen receptor (AR)-mediated effects of androgenic progestins (eg, NETA, tibolone, levonorgestrel, etc) on bone in women remains unclear. In mice, loss of the AR results in bone loss in males but not females.…”

Section: Pharmacologic Basis Of Add-back Therapy: Role Of Estrogen and Progesteronementioning

confidence: 99%

The Hormonal Profile of Norethindrone Acetate: Rationale for Add-Back Therapy With Gonadotropin-Releasing Hormone Agonists in Women With Endometriosis

2012

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Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.

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Long-term effects of progestins on bone quality and fractures

Cited by 6 publications

References 70 publications

The clinical relevance of progestogens in hormonal contraception: Present status and future developments

The clinical relevance of progestogens in hormonal contraception: Present status and future developments

Bone health in estrogen-free contraception

The Hormonal Profile of Norethindrone Acetate: Rationale for Add-Back Therapy With Gonadotropin-Releasing Hormone Agonists in Women With Endometriosis

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