Active ingredient: Estradiol

Brand Name: Estrofem, Zumenon, Elleste Solo, Estradot, Evorel, Estraderm, FemSeven, Systen, Estramon, Oestrogel, Estreva, Sandrena, Gynokadin, Lenzetto, Evamist, Vagifem, Vagirux, Estring

Drug class: Estrogens

Mechanism of Action:

Estrogen-containing medicines are available in systemic and local formulations, including oral, transdermal, and vaginal preparations. Their effects on fertility biomarkers depend on the estrogen used, dose, route of administration, systemic exposure, and duration of treatment.
Mechanism of action and use
Estrogens act primarily through estrogen receptors (ERα and ERβ) in reproductive and other estrogen-responsive tissues. Depending on the dose and route of administration, estrogen-containing medicines may produce predominantly local effects or clinically relevant systemic estrogen exposure.
Systemic estrogen preparations, including oral and transdermal estradiol, are primarily used for the treatment of estrogen deficiency and menopausal symptoms. Vaginal estrogen preparations, including creams, tablets/inserts, and rings, are mainly used for genitourinary symptoms associated with estrogen deficiency.
Systemic exposure varies considerably between vaginal formulations. Low-dose vaginal estrogen generally results in limited systemic exposure, although absorption depends on the specific product and dose.
High-strength vaginal estradiol is an important exception. The EMA concluded that vaginal creams containing 100 micrograms/g (0.01%) estradiol can produce systemic estradiol concentrations above the normal postmenopausal range and therefore restricted their use to a single treatment period of up to four weeks.
At sufficiently high systemic exposure, estrogen can suppress gonadotropin secretion and ovarian activity. However, this effect should not be generalized to all estrogen-containing medicines, particularly low-dose vaginal preparations.

Effect on fertility biomarkers

The effect of estrogen-containing medicines on ovulation depends on systemic exposure, dose and formulation. Pharmacological doses of transdermal estradiol have been shown to suppress ovarian activity and ovulation. Study on transdermal estradiol and ovulation Evidence for low-dose vaginal estradiol is limited and does not establish routine suppression of ovulation. There is insufficient evidence that estrogen-containing medicines consistently alter natural menstrual-cycle length. Treatment may change the timing or pattern of uterine bleeding, but these changes should not necessarily be interpreted as changes in ovulation or cycle length. Cervical mucus is the fertility biomarker most directly affected by estrogen. Exogenous estrogen can increase mucus production and produce fertile-type characteristics, including greater clarity, slipperiness and stretchability. In a study of transdermal estradiol, estrogen administration produced cervical mucus scores comparable to those observed during natural cycles. Study on transdermal estradiol and cervical mucus Consequently, fertile-type mucus during estrogen treatment may reflect the pharmacological effect of the medication rather than endogenous ovarian activity and may therefore be less reliable for identifying impending ovulation. Estrogen does not produce the characteristic sustained postovulatory increase in basal body temperature, which is primarily associated with progesterone. Estrogen may influence thermoregulation, and estrogen therapy has been associated with changes in body temperature, but these effects should not be interpreted as a progesterone-mediated postovulatory temperature shift.

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Ovulation, Mucus

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References:

Smith RN, Studd JW, Zamblera D, Holland EF. A randomised comparison over 8 months of 100 micrograms and 200 micrograms twice weekly doses of transdermal oestradiol in the treatment of severe premenstrual syndrome. Br J Obstet Gynaecol. 1995 Jun;102(6):475-84. doi: 10.1111/j.1471-0528.1995.tb11321.x. PMID: 7632640. Santen RJ, Mirkin S, Bernick B, Constantine GD. Systemic estradiol levels with low-dose vaginal estrogens. Menopause. 2020 Mar;27(3):361-370. doi: 10.1097/GME.0000000000001463. PMID: 31794498; PMCID: PMC7050796. Gudmundsson A, Goodman B, Lent S, Barczi S, Grace A, Boyle L, Ershler WB, Carnes M. Effects of estrogen replacement therapy on the circadian rhythms of serum cortisol and body temperature in postmenopausal women. Exp Gerontol. 1999 Sep;34(6):809-18. doi: 10.1016/s0531-5565(99)00044-3. PMID: 10579640. Han L, Padua E, Edelman A, Jensen JT. Appraising cervical mucus: a new approach to evaluating contraceptives. Eur J Contracept Reprod Health Care. 2018 Feb;23(1):78-83. doi: 10.1080/13625187.2018.1437134. Epub 2018 Feb 19. PMID: 29457758.

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Disclaimer: The information provided may not include all possible interactions or side effects of medication. The effects on fertility biomarkers can vary and may depend on the dosage, how long the medication is used, the medical condition, or other factors. This database is for informational purposes only and should not replace professional medical advice, diagnosis, or treatment. Always consult your healthcare provider or a qualified health professional if you have questions about medications, fertility, or medical conditions.