Do pesticides, herbicides or hormonal replacement contribute to melanoma?

The short answer?  No.  Yes.  No.  Here's the deal:

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis. Stanganelli, De Felici, Madnel, et al.  J Eur Acad Dermatol Venereol. 2019 Sep 21.

The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM.  To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development.

A systematic review of the literature was performed up to September 2018 using Medline, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Priory criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimates heterogeneity was assessed and publication bias investigated.

A total of 9 studies (2 case-controls and 7 cohorts) comprising 184389 unique subjects were included. The summary relative risks for the categories "herbicides - ever exposure", "insecticides - ever exposure", "any pesticide - ever exposure" and "any pesticide - high exposure" resulted 1.85, 1.57, 1.31 and 2.17, respectively. Herbicides and insecticides had no between-study heterogeneity, while a significant heterogeneity was detected for the high exposure to any pesticide. No indication for publication bias was found.

Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

So, basically - YES!!!  The pesticide issue is a little unclear, but folks exposed to herbicides (like Round Up, etc.) ARE at increased risk for cutaneous melanoma.

Now this:

Premenopausal Use of Progestogens and Cutaneous Melanoma Risk: A French Prospective Cohort Study.  Cervenka, Rahmoun, Mahamat-Saleh et al.  Am J Epidemiol. 2019 Oct 29. 

The influence of sex hormones on melanoma risk has been suggested, but the influence of premenopausal use of progestogens on this cancer has never been investigated. E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale) is a prospective cohort of 98,995 French women aged 40-65 years at inclusion. We used Cox models adjusted for age and melanoma risk factors. Over 1992-2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk  which was reduced after adjustment for melanoma risk factors. There was no heterogeneity across types of progestogens, and use of multiple progestogens was positively associated with melanoma risk. Among users, we found no relation with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results.

Exogenous Hormone Use and Cutaneous Melanoma Risk in Women: The European Prospective Investigation Into Cancer and Nutrition.  Cervenka, Al Rahmoun, Mahamat-Saleh, et al. Int J Cancer. 2019 Sep 10. 

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires.  Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, where of 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk, with no detected heterogeneity across countries. This risk increased linearly with duration of use. Among postmenopausal women, ever use of MHT was associated with a non-significant increase in melanoma risk overall, which was heterogeneous across countries. Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

So, basically, though some self-reported answers on questionnaires demonstrated vague associations between oral contraceptive use and melanoma, overall, there was no significant increased risk for the development of melanoma and postmenopausal hormone replacement. 

Then, there's this, added 12/7/2019:

Hormone replacement therapy and the risk of melanoma in post-menopausal women.  Hicks, Kristensen, Pedersen, et al.  Hum Reprod.  2019 Dec 5

Is hormone replacement therapy (HRT) associated with an increased risk of melanoma skin cancer or prognostic outcomes amongst post-menopausal women?  Whilst we found evidence of an association with melanoma risk, the lack of dose-response and associations observed with recent use, localised disease and intravaginal oestrogens suggests this is a non-causal association.  Evidence on HRT and melanoma risk remains inconclusive, with studies providing conflicting results. Furthermore, evidence on melanoma survival is sparse, with only one previous study reporting protective associations with HRT use, likely attributable to immortal time bias.

We conducted a nation-wide population-based case-control study and a retrospective cohort study utilising the Danish healthcare registries. Case-control analyses included 8279 women aged 45-85 with a first-ever diagnosis of malignant melanoma between 2000 and 2015, matched by age and calendar time to 165 580 population controls. A cohort of 6575 patients with a diagnosis of primary malignant melanoma between 2000 and 2013 and followed through 2015 was examined to determine if HRT use had an impact on melanoma survival outcomes.

Based on prescriptions dispensed since 1995, ever-use of HRT was defined as having filled at least one prescription for HRT prior to the index date. In total, 2629 cases (31.8%) and 47 026 controls (28.4%) used HRT.

High use of HRT was associated with an OR of 1.21  for melanoma risk, with no evidence of a dose-response pattern. Results were most pronounced amongst recent high users, for localised disease and for intravaginal oestrogen therapy. Compared with non-use, there was no evidence of an association for secondary melanoma for post-diagnostic new-use or continuous HRT use. Similar associations were observed for all-cause mortality.

Despite the large sample size and the use of robust population-based registries with almost complete coverage, we lacked information on some important confounders including sun exposure.

Whilst we cannot rule out an association between HRT use and melanoma risk, the associations observed are also compatible with increased healthcare utilisation and thus increased melanoma detection amongst HRT users. No association between HRT use and melanoma survival outcomes was observed. This should provide some reassurance to patients and clinicians, particularly concerning the use of HRT in patients with a history of melanoma.

There is obviously much we do not understand about melanoma period.  We certainly lack a clear understanding regarding the implications of being female and the role pregnancy plays in melanoma:  Women and melanoma risk  These studies add to a start.  The more you know. - c